viral diseases - mechanisms of microbial infections
TRANSCRIPT
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
1/105
• TARGET CELLS, VIRAL PATHOGENICITY, AND
VIRAL REPLICATION CYCLE. – Ligand (viral envelope or capsid proteins)‐receptor
common to all cells are used by viruses to attach
– Enveloped, non‐enveloped virus
– s. v rus n rep ca on cyc e
1
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
2/105
Fig. 4‐30 Ligand‐receptor interactions. Ligand (viral envelope or capsid proteins)‐receptor
(host cell membrane proteins) interactions common to all cells are used by viruses to attach
to and infect specific target cells.2
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
3/105
Fig. 4‐32A Morphology of viruses. A, Nonenveloped viruses. They attach to host cells using a
protein coat (viral coat, capsid, capsomeres) and usually kill infected cells to release newly
formed virus. B, Enveloped viruses. They attach to host cells using a viral envelope and usually
do not kill infected cells to release newly formed virus. (From Goering R, Dockrell H, Roitt I, et al:
Mims’
medical
microbiology, ed 4, St. Louis, 2008, Mosby.)3
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
4/105
Fig. 4‐32B Morphology of viruses. A, Nonenveloped viruses. They attach to host cells using a protein coat
, , . ,
viruses. They attach to host cells using a viral envelope and usually do not kill infected cells to release newly formed virus. (From Goering R, Dockrell H, Roitt I, et al: Mims’ medical microbiology, ed 4, St. Louis, 2008,
Mosby.)4
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
5/105
Fig. 4‐31 Virus replication cycle. Stages in the
infection, replication, and egress of a virus in a
target cell. Several thousand virus particles
may be formed within each infected cell. (From
Rosenthal KS, Tan JS: Rapid review
microbiology
and
immunology, ed 2, St. Louis,
2007, Mosby.)5
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
6/105
Fig. 4‐33A Replication of DNA and RNA
viruses. (From Goering R, Dockrell H, Roitt I, et
al: Mims’ medical microbiology, ed 4, St. Louis,
2008, Mosby.)
6
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
7/105
Fig. 4‐33B Replication of DNA and RNA
viruses. (From Goering R, Dockrell H, Roitt I, et
al: Mims’
medical
microbiology, ed 4, St. Louis,
2008, Mosby.)
7
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
8/105
Fig. 4‐34 Actions of viral proteins.
affect normal cell function through
mechanisms illustrated here. (From
Kumar V Abbas A Fausto N et al:
Robbins
&
Cotran pathologic
basis
of
disease, ed 8, Philadelphia, 2009,
Saunders.)
8
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
9/105
ru ence e erm na es – Control the process involved in
• Replication, including attachment to, replication in, and release of virus from
• Escaping, modulating, or suppressing the host innate and adaptive immune response
• Purpose?
•
Mechanism of genomic change – Genomic variation, genetic diversity, acquired new virulent
determinates
– Genetic drift, spontaneous mutation
– Genetic shift, • reassortment• recombination,
• Defective interfering virus
• major change of virus protein
9
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
10/105
Fig. 4‐35 Antigenic shifts in influenza virus. One theory proposes that antigenic shifts occur when a human
influenza virus blue and an avian influenza virus red coinfect a s ecies that is ermissive for both. The 8
ssRNA strands are co‐expressed in the same infected cell, resulting in mixing of the strands so that a hybrid
virus can be produced. The hybrid virus indicated here contains all the genetic information of the original
virus that infected humans, but contains a new hemagglutinin (HA)‐containing strand from the avian virus.
s v rus expresses a new an gen an w e ess suscep e o res ua mmun y a norma y
provides partial protection against yearly influenza infections. (From McCance KL: Pathophysiology:
The biologic
basis
for
disease
in
adults
and
children, ed 6, St. Louis, 2010, Mosby.) 10
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
11/105
• Defense mechanism
– Infection? Susce tibilit ?
– Innate and adaptive immune system
.
• i.e., T cell function, Interferon
11
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
12/105
Fig. 4‐36 Possible
roles
for
T lymphocytes
in
immunity
to
intracellular
microorganisms.
A, The
T lymphocyte activates intracellular killing mechanisms by secretion of cytokines such as IFNγ,
e.g., in a macrophage. B, The T lymphocyte directly kills cell and parasite. C, The T lymphocyte
destroys vital tissue in the process of killing the parasite. D, By lysing cells the T lymphocyte
allows still‐living parasites to disseminate. E, Parasites released in this way may be phagocytosed
by a more effective host cell. (From Goering R, Dockrell H, Roitt I, et al: Mims’
medical
microbiology, ed 4, St. Louis, 2008, Mosby.) 12
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
13/105
Fig. 4‐37 Actions of interferon (IFN) in viral infection of target cells. (From McCance KL:
Pathophysiology:
The
biologic
basis
for
disease
in
adults
and
children, ed 6, St. Louis, 2010,
Mosby.)
13
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
14/105
• Mechanisms of injury in diseases caused by
virus (Table 4‐4) – Cell lysis
–
– Inflammation
– Neoplastic transformation
– Cell dysfunction
14
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
15/105
Rinder est(Cattle Plaque, Morbillivirus, Enveloped RNA Virus)
• Simi arities wit t ree vira iseases in c inica
presentation, lesions, causative virus and mechanisms of infection and spread
– Morbillivirus, local, regional and systemic infection
and spread and their target cells, canine distemper
– Bovine viral diarrhea‐mucosa disease, clinical
presentation and lesions – Parvoviruses, mechanisms used to infect and
spread between cells.
15
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
16/105
Rinder est(Cattle Plaque, Morbillivirus, Enveloped RNA Virus)
• ec an sms o n ury: ys unc on an ea o mucosa ep e a ce s, en r c ce s, ce s,
lymphocytes and macrophage in GI
• Lesions: erosions, ulcerations and hemorrhages of the oral cavity and small intestine over Peyer’s patch.
Edema and hemorrhage in the mesentery lymph node.
• Virus entry:
– inhaled, deposited on and trapped in the mucosa
– Penetrate mucus layer and reach mucosa layer (mechanism?)
– n ec on o sur ace an reg ona ymp o ce s, macrop ages, an ymp no e v a eu ocy e
trafficking
– Systemic infection through Leukocyte trafficking or blood circulation.
– Enterocyte infection:
• GI?
• Peyer’s patch then adjacent enterocytes
•
Polarized pattern, restricted to the basolateral area, the area nearest to peyer’s patch and M ce s
• Mucosal ulceration and shedding virus in alimentary tract
• Has envelope and hemagglutinin/fusion surface glycoproteins for attachment and fusion, Vs. host cell
membrane glycoprotein receptor CD150 (signaling lymphocyte activation molecule (SLAM)
– SLAM has been demonstrated on the membrane of lymphocytes, monocytes, macrophages,
epithelial cells of respiratory, alimentary and integumentary systems16
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
17/105
Fig. 4‐38A Rinderpest.
A, Oral mucosa, dental pad. Note the erosions and ulcers (arrows) adjacent to the
dental pad caused by Rinderpest virus. B, Oral mucosa. Focal aggregates of epithelial cells in the mucosa are
swollen necrotic and some are detached arrows . When abraded b in esta or other trauma the
mechanical force applied to the lesion in A can separate the epithelium overlying the lesion and it will grow
and lead to ulcers or abrasions, depending on depth of the epithelial loss. Note the acute inflammatory
response in the lamina propria. H&E stain. C, Ileum. The mucosa overlying Peyer’s patches is ulcerated and covere w t r n m xe w t emorr age arrows . s es on appears to resu t rom sprea o t e v rus
from underlying lymphocytes in Peyer’s patches to epithelial cells of the crypts. D, Epithelial cells of the
crypts are hyperplastic and form syncytia (arrow). In other areas, crypt enterocytes and cells in the adjacent
lamina ro ria are necrotic arrowhead and accom anied b acute inflammation. This rocess leads to
ulceration of the intestinal mucosa. H&E stain. (A and C courtesy Dr. C. Brown, College of Veterinary
Medicine, The University of Georgia. B and D courtesy Dr. J.F. Zachary, College of Veterinary Medicine,
University of Illinois.) 17
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
18/105
Fig. 4‐38B Rinderpest.
A, Oral mucosa, dental pad. Note the erosions and ulcers (arrows) adjacent to the
dental pad caused by Rinderpest virus. B, Oral mucosa. Focal aggregates of epithelial cells in the mucosa are
swollen, necrotic, and some are detached (arrows). When abraded by ingesta or other trauma, the
mechanical force applied to the lesion in A can separate the epithelium overlying the lesion and it will grow
and lead to ulcers or abrasions, depending on depth of the epithelial loss. Note the acute inflammatory
response in the lamina propria. H&E stain. C, Ileum. The mucosa overlying Peyer’s patches is ulcerated and
.
from underlying lymphocytes in Peyer’s patches to epithelial cells of the crypts. D, Epithelial cells of the
crypts are hyperplastic and form syncytia (arrow). In other areas, crypt enterocytes and cells in the adjacent
lamina propria are necrotic (arrowhead) and accompanied by acute inflammation. This process leads to
ulceration of the intestinal mucosa. H&E stain. (A and C courtesy Dr. C. Brown, College of Veterinary
Medicine, The University of Georgia. B and D courtesy Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.) 18
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
19/105
Fig. 4‐38C Rinderpest. A, Oral mucosa, dental pad.
Note the erosions and ulcers (arrows) adjacent to
the dental pad caused by Rinderpest virus. B, Oral
mucosa. oca agg ega es o ep e a ce s n e
mucosa are swollen, necrotic, and some are
detached (arrows). When abraded by ingesta or
other trauma, the mechanical force applied to the
lesion in A can separate the epithelium overlying the
lesion and it will grow and lead to ulcers or abrasions,
depending on depth of the epithelial loss. Note the .
H&E stain. C, Ileum. The mucosa overlying Peyer’s
patches is ulcerated and covered with fibrin mixed
with hemorrhage (arrows). This lesion appears to
result from spread of the virus from underlying
lymphocytes in Peyer’s patches to epithelial cells of
the crypts. D, Epithelial cells of the crypts are
.
areas, crypt enterocytes and cells in the adjacent
lamina propria are necrotic (arrowhead) and
accompanied by acute inflammation. This process leads to ulceration of the intestinal mucosa. H&E
stain. (A and C courtesy Dr. C. Brown, College of
Veterinary Medicine, The University of Georgia. B
. . . ,
Medicine, University of Illinois.)
19
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
20/105
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
21/105
Parvovirus Enteritis(non enveloped DNA virus)
• an ne an e ne parvov rus en er s
•
Mechanism of injury is death of crypt epithelial
marrow.
, hemorrhage, acute inflammation and fibrin exudates
• Infection required a host cell‐derived duplex
transcri tion tem late onl available in cell under S‐phase of the cell cycle. – Unable to turn on DNA synthesis in host cells,
21
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
22/105
Parvovirus Enteritis(non enveloped DNA virus)
• rus entry:
– Inhaled or ingested, deposited on mucosa or trapped in mucus layer
– How the virus reach to mucosa layer? – Spreading: leukocyte trafficking or cell free virus disseminated
– Experimentally, virus reach peyer’s patch is earlier before it reach contiguous crypt
enterocytes
– o ar ze pattern n ect on, restr cte to t e aso atera area, t e area nearest to peyer s
patch and M cells
• Cell receptor, dog: capsid protein bind to transferrin receptors; cat: neuramini acid and
• Osmotic malabsorption and maldigestion diarrhea, enterocytes killed and sloughed from
mucosa after viral replication completion,
– Life s an of enteroc te 48h
– Lost of supplement of enterocyte from crypt epithelium
– Lost of digestive function of enterocyte
–
–
Barrier lost and exposed lamina propria – Fermentation of bacteria and endotoxin perfusion, enterotoxic shock and DIC 22
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
23/105
Fig. 7‐160A Parvovirus enteritis, small intestine, dog. A, Segments of the small intestine are diffusely reddened (active hyperemia of the mucosa), and the serosal
intestine is necrotic. Note the roughened, granular, focally petechiated, and focally sloughing mucosa. (A courtesy College of Veterinary Medicine, University of Illinois. Bcourtesy Department of Veterinary Biosciences, College of Veterinary Medicine, The
’ , , University of Georgia.)
23
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
24/105
24
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
25/105
25
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
26/105
26
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
27/105
27
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
28/105
Transmissible Gastroenteritis
(Enveloped RNA virus)
• Mec an sm o n ury s ys unct on an eat o ep t e a ce s v us enterocytes
covering tip and sides of intestinal villi.
• Lesions: congestion and thinning of small GI wall, shortening (atrophy) of villi.
• Virus entry:
– Ingestion and swallowing
–
– Viral envelope S protein facilitates its entry into villus enterocytes• Bind sialic acid (mucin like glycoproteins) in the mucus
• Bind aminopeptidase N, expressed on apica sur ace o vi us enterocytes
• Cell killed and sloughed, but could be replaced
• A malabsorption osmotic diarrhea occurred
• Carbohydrate accumulated, bacterial fermentation, denuded epithelium may be
susceptible to bacterial toxin which affects cardiovascular and hemodynamic
s stem
28
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
29/105
‐.
target villus absorptive enterocytes. A,
Transmissible gastroenteritis virus and
villus enterocytes and cause disease. B, Small
intestine, villus atrophy. Following the initial
loss of ti enteroc tes arrows the villi
contract, reducing the surface area to be reepithelialized. Note the crypt epithelium
becomes hyperplastic with numerous mitoses
and the villi are covered by a less specialized,
usually low cuboidal epithelium. The villus
lamina propria is infiltrated by acute inflammatory cells. H&E stain. (A from Goering
R, Dockrell H, Roitt I, et al: Mims’ medical
microbiology, ed 4, St. Louis, 2008, Mosby. B
courtesy Dr. J. F. Zachary, College of Veterinary
Medicine, University of Illinois.) 29
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
30/105
Fig. 4‐39B Mechanism of viral infections that target villus absorptive enterocytes. A, Transmissible
gastroenteritis virus and rotavirus use similar mechanisms to infect villus enterocytes and cause disease. B,Small intestine, villus atrophy. Following the initial loss of tip enterocytes (arrows), the villi contract, reducing
the surface area to be reepithelialized. Note the crypt epithelium becomes hyperplastic with numerous
mitoses and the villi are covered by a less specialized, usually low cuboidal epithelium. The villus lamina
. . , , ,
Mims’ medical microbiology, ed 4, St. Louis, 2008, Mosby. B courtesy Dr. J. F. Zachary, College of Veterinary
Medicine, University of Illinois.) 30
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
31/105
Foot and Mouth Disease(Aphthovirus, nonenveloped RNA virus)
• ec an sms o n ury: s m ar o sw ne ves cu ar sease and vesicular exanthema of pigs, cell dysfunction and death
leading to intercellular edema (vesiculation), rupture of vesicles and subsequent erosions and ulcers on the mucosa and skin.
•
• Inhalation or ingestion, established local infection, then regional lymphoid tissue, then systemic spread
• Systemically to infect, replicate in and lysed epithelial cells of stratum spongiosum of mucosa and skin resulting in
vesicles.• Capsid protein, VP1‐4 as a ligand; α‐integrin (Vβ1, Vβ3,
and Vβ6) expressed in the host cells are used as receptor.
31
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
32/105
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
33/105
FMD
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
34/105
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
35/105
Fig. 4‐40A Foot‐and‐mouth disease. A, Ox. Note the ulcer on the mucosa of the upper dental
pad. Such ulcers begin as fluid‐filled vesicles that rupture usually from the trauma of mastication
or prehension. Vesicles and ulcers that result from their rupture may occur on all mucosae of
the body including the dental pad, tongue, gingiva, coronary bands, and teats as examples. B,The mucosa has a large focus of a previous vesicle, which is now partially filled with edema fluid,
fibrin, cellular debris, and acute inflammatory cells forming a pustule. H&E stain. (A courtesy Dr.
M. Adsit, College of Veterinary Medicine, The University of Georgia and Noah’s Arkive, College
of Veterinary Medicine, The University of Georgia. B courtesy Dr. C. Brown, College of Veterinary
Medicine, The University of Georgia.) 35
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
36/105
Fig. 4‐40B Foot‐and‐mouth disease. A, Ox. Note the ulcer on the mucosa of the upper dental pad. Such
u cers eg n as u ‐ e ves c es t at rupture usua y rom t e trauma o mast cat on or pre ens on.
Vesicles and ulcers that result from their rupture may occur on all mucosae of the body including the dental
pad, tongue, gingiva, coronary bands, and teats as examples. B, The mucosa has a large focus of a previous
vesicle which is now artiall filled with edema fluid fibrin cellular debris and acute inflammator cells
forming a pustule. H&E stain. (A courtesy Dr. M. Adsit, College of Veterinary Medicine, The University of
Georgia and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. C.
Brown, College of Veterinary Medicine, The University of Georgia.)36
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
37/105
Infectious Bovine Rhinotracheitis(bovine herpesvirus, alphaherpesvirus, enveloped DNA virus)
• ec an sms o n ury, ea o c a e mucoc aryapparatus) and nonciliated epithelial cells of the oral, nasal,
pharyngeal, and respiratory mucosa.• Lesions: hyperemia, hemorrhage, edema, and necrosis
leading to large areas of mucosal erosions and ulcers often .
• Virus entry: – inhaled and ingested , trapped in the mucus
– Ligand‐receptor: • viral envelope glycoprotein B, C, D are used to attach and enter a
variety of host target cells via an array of glycoaminoglycan receptor suc as erpesv rus entry me ator A, net n 1 an 2 erpes entry protein C and B), and 3‐o‐sulfated heparin sulfate, commonly express on the mucosa epithelium and sensory nerve endings.
37
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
38/105
Infectious Bovine Rhinotracheitis(bovine herpesvirus, alphaherpesvirus, enveloped DNA virus)
• rus en ry: – Gain access to sensory nerve endings in the
, retrograde axonal transport and to other CNS • Nerve cells: reservoir, no MHCII and low concentration of
, ess e y e ng recogn ze y mmune surve ance
• During latency, not antigen (viral protein) are synthesized
– With activation virus re‐establishes its re lication cycle and through axonal transport mechanism spread back to the nerve ending of the mucosa, infect
.
38
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
39/105
Infectious Bovine Rhinotracheitis(bovine herpesvirus, alphaherpesvirus, enveloped DNA virus)
• erpes pro e ns – Disrupt the synthesis of the interferon
– Block the reco nition of virus‐infected cells b c totoxic T lymphocytes
– Block the homing of T lymphocytes to viral‐infected cells
,
thus suppressing the adaptive immune response to virus.• Infected cells are more susceptible to bacterial infection
like pasteurellosis and Mannheimioisis – Immune suppression
–
endings.
39
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
40/105
Fig. 4‐41 Mechanism
of mucosal
infections
caused by
.
For simplification, the
epithelium is
represented as one cell thick. (From Goering R,
Dockrell H, Roitt I, et al:
Mims’
medical
, , .
Louis, 2008, Mosby.)
40
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
41/105
Classical Swine Fever (Hog Cholera, Pestivirus, enveloped RNA virus)
• ec an sms o n ury, ea o en o e a ce s o mu p e organ systems and of hemopoietic cells.
• Lesions: hemorrha e in multi le or ans kidne and s leen necrosis in the palatine tonsil.
• Viral entry: – ngest on an e y n a at on, mec an ca trans er ve c e or
instruments) – Infect and replicate in tonsil crypt
– How to penetrate mucus layer?
– Erns and E2 and other envelop glycoproteins are ligand and bind
to cell surface l cosamino l can like he arin sulfate – Leukocyte trafficking and cell free viremia, regional replication
and systemic spreading
41
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
42/105
Classical Swine Fever (Hog Cholera, Pestivirus, enveloped RNA virus)
• n ot e a n ury
– Infected macrophages interact with cells by adhering to and migrating through
endothelium, likely by activating the leukocytes adhesion cascade
– ec n u y o n ec e en o e a ce s cause acu e n amma o y esponse.
– Lesions: endothelial swelling, degeneration, and necrosis, and acute and chronic
inflammation.
– ,
hemorrhage in many tissues and organs, like in kidney.• Hemopoietic cell injury
– .
– Infects and kill these cells,
– Severely impaired adaptive immune response
–
– Decrease number of phagocytes
– Decreased cell mediated immune response
–
42
Fig. 4‐42A Classical swine fever (hog cholera). Lesions in
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
43/105
classical swine fever are similar to those observed in
‐
for lesions of African swine fever. A, The tonsil (of
the
soft
palate), a tissue of choice for isolation and identification of
the virus, contains foci of hemorrhage and necrosis
arrows , t e resu t o necros s o mucosa ep t e a ce s n
tonsillar crypts and necrosis of the adjacent endothelial
cells and lymphocytes in the lamina propria from infection
with virus. B Kidne . The cortical surface has numerous
randomly distributed petechia caused by injury to and
subsequent necrosis of endothelial cells following their
infection with classical swine fever virus. C, Mesenteric
ymp no es arrows are en arge an congeste ue to
vascular injury caused by virus, resulting in blood in the subcapsular sinuses. D, Tonsillar crypt lymphoid nodules.
Note the focal necrosis of l m hoc tes ri ht lower hal o
image) in the nodules caused by infection with virus. H&E
stain. (A courtesy Dr. R. Breeze, Plum Island Animal Disease
Center and Noah’s Arkive, College of Veterinary Medicine,
e n vers ty o eorg a. courtesy r. . regg, um
Island Animal Disease Center and Noah’s Arkive, College of
Veterinary Medicine, The University of Georgia. C courtesy
Dr. M.D. McGavin Colle e of Veterinar Medicine
University of Tennessee. D courtesy Dr. J.F. Zachary, College
of Veterinary Medicine, University of Illinois.) 43
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
44/105
F g. 4‐4 B ass ca sw ne ever og c o era . Les ons n c ass ca sw ne ever are s m ar to t ose o serve
in African swine fever, but usually less severe. See Fig. 4‐43 for lesions of African swine fever. A, The tonsil (of the
soft
palate), a tissue of choice for isolation and identification of the virus, contains foci of hemorrhage
and necrosis arrows the result of necrosis of mucosal e ithelial cells in tonsillar cr ts and necrosis of the
adjacent endothelial cells and lymphocytes in the lamina propria from infection with virus. B, Kidney. The
cortical surface has numerous randomly distributed petechia caused by injury to and subsequent necrosis of
endothelial cells following their infection with classical swine fever virus. C, Mesenteric lymph nodes (arrows)
are en arge an congeste ue to vascu ar n ury cause y v rus, resu t ng n oo n t e su capsu ar
sinuses. D, Tonsillar crypt lymphoid nodules. Note the focal necrosis of lymphocytes (right lower half of
image) in the nodules caused by infection with virus. H&E stain. (A courtesy Dr. R. Breeze, Plum Island
Animal Disease Center and Noah’s Arkive Colle e of Veterinar Medicine The Universit of Geor ia. B
courtesy Dr. D. Gregg, Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine,
The University of Georgia. C courtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee. D courtesy Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.)
44
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
45/105
F g. 4‐4 ass ca sw ne ever og c o era . Les ons n c ass ca sw ne ever are s m ar to t ose o serve
in African swine fever, but usually less severe. See Fig. 4‐43 for lesions of African swine fever. A, The tonsil (of the
soft
palate), a tissue of choice for isolation and identification of the virus, contains foci of hemorrhage
and necrosis arrows the result of necrosis of mucosal e ithelial cells in tonsillar cr ts and necrosis of the
adjacent endothelial cells and lymphocytes in the lamina propria from infection with virus. B, Kidney. The
cortical surface has numerous randomly distributed petechia caused by injury to and subsequent necrosis of
endothelial cells following their infection with classical swine fever virus. C, Mesenteric lymph nodes (arrows)
are en arge an congeste ue to vascu ar n ury cause y v rus, resu t ng n oo n t e su capsu ar
sinuses. D, Tonsillar crypt lymphoid nodules. Note the focal necrosis of lymphocytes (right lower half of
image) in the nodules caused by infection with virus. H&E stain. (A courtesy Dr. R. Breeze, Plum Island
Animal Disease Center and Noah’s Arkive Colle e of Veterinar Medicine The Universit of Geor ia. B
courtesy Dr. D. Gregg, Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine,
The University of Georgia. C courtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee. D courtesy Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.)
45
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
46/105
F g. 4‐4 D ass ca sw ne ever og c o era . Les ons n c ass ca sw ne ever are s m ar to t ose o serve
in African swine fever, but usually less severe. See Fig. 4‐43 for lesions of African swine fever. A, The tonsil (of the
soft
palate), a tissue of choice for isolation and identification of the virus, contains foci of hemorrhage
and necrosis arrows the result of necrosis of mucosal e ithelial cells in tonsillar cr ts and necrosis of the
adjacent endothelial cells and lymphocytes in the lamina propria from infection with virus. B, Kidney. The
cortical surface has numerous randomly distributed petechia caused by injury to and subsequent necrosis of
endothelial cells following their infection with classical swine fever virus. C, Mesenteric lymph nodes (arrows)
are en arge an congeste ue to vascu ar n ury cause y v rus, resu t ng n oo n t e su capsu ar
sinuses. D, Tonsillar crypt lymphoid nodules. Note the focal necrosis of lymphocytes (right lower half of
image) in the nodules caused by infection with virus. H&E stain. (A courtesy Dr. R. Breeze, Plum Island
Animal Disease Center and Noah’s Arkive Colle e of Veterinar Medicine The Universit of Geor ia. B
courtesy Dr. D. Gregg, Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine,
The University of Georgia. C courtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee. D courtesy Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.)
46
Af i S i F
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
47/105
African Swine Fever
(Asfivirus, enveloped DNA virus)
• Mechanisms of injury
– Similar to CSFV
– But more severe
• Virus entry
– In addition to the entry routes of CSFV, African swine fever
virus can gain access to the blood vascular system and
– Hemopoietic cell injury
– ra g ycopro e n p , p , an p are e gan s or e
attachment and entering into target cells, receptor is not
–
DIC leading to collapse of the circulatory system and shock is likel the cause of death in the infected i s.
47
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
48/105
Fig. 4‐43A African
swine
fever. Lesions in African swine fever are similar to those observed in classical
swine fever, but usually much more severe. See Fig. 4‐42 for lesions of classical swine fever. A, Epicardium
and ericardial cavit . The e icardium and sub acent m ocardium have numerous randoml distributed
ecchymoses caused by injury to and subsequent necrosis of endothelial cells from infection with African
swine fever virus. Note the accumulation of a fibrinous effusion in the pericardial cavity. B, Splenomegaly,
bloody spleen. The spleen is congested with blood and friable as a result of vascular damage caused by the
v rus. Lymp no es not s own ere are a so congeste an e ematous see c ass ca sw ne ever . ,
Endothelial cells and lymphoid cells of white pulp of the spleen are necrotic (e.g., pyknosis, karyolysis). H&E
stain. D, Endothelial cells lining sinusoids of the liver are necrotic (e.g., pyknosis, karyolysis). Also note the
necrosis of some he atoc tes. H&E stain. A courtes Dr. C. Brown Colle e of Veterinar Medicine The
University of Georgia. B courtesy Dr. D. Gregg, Plum Island Animal Disease Center and Noah’s Arkive, College
of Veterinary Medicine, The University of Georgia. C and D Courtesy Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.)
48
Fig. 4‐43B African swine fever. Lesions in African
swine fever are similar to those observed in classical
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
49/105
swine fever, but usually much more severe. See Fig.
4‐4 or es ons o c ass ca sw ne ever. A,
Epicardium and pericardial cavity. The epicardiumand subjacent myocardium have numerous randomly
distributed ecch moses caused b in ur to and
subsequent necrosis of endothelial cells from
infection with African swine fever virus. Note the
accumulation of a fibrinous effusion in the per car a cav y. , p enomega y, oo y sp een.
The spleen is congested with blood and friable as a
result of vascular damage caused by the virus. Lymph
nodes not shown here are also con ested and
edematous (see classical swine fever). C, Endothelial
cells and lymphoid cells of white pulp of the spleen
are necrotic (e.g., pyknosis, karyolysis). H&E stain. D,
n o e a ce s n ng s nuso s o e ver are
necrotic (e.g., pyknosis, karyolysis). Also note the
necrosis of some hepatocytes. H&E stain. (A courtesy
Dr. C. Brown, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. D. Gregg, Plum
Island Animal Disease Center and Noah’s Arkive,
College of Veterinary Medicine, The University of
eorg a. an our esy r. . . ac ary, o ege o
Veterinary Medicine, University of Illinois.)
49
Fig. 4‐43C African swine fever. Lesions in African
swine fever are similar to those observed in classical
f
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
50/105
swine fever, but usually much more severe. See Fig.
‐ or es ons o c ass ca sw ne ever. ,
Epicardium and pericardial cavity. The epicardiumand subjacent myocardium have numerous randomly
distributed ecchymoses caused by injury to and
subsequent necrosis of endothelial cells from
infection with African swine fever virus. Note the
accumulation of a fibrinous effusion in the
pe ca a cav y. , p enomega y, oo y sp een.
The spleen is congested with blood and friable as a
result of vascular damage caused by the virus. Lymph
nodes (not shown here) are also congested and
edematous (see classical swine fever). C, Endothelial
cells and lymphoid cells of white pulp of the spleen
are necrotic (e.g., pyknosis, karyolysis). H&E stain. D,
necrotic (e.g., pyknosis, karyolysis). Also note the
necrosis of some hepatocytes. H&E stain. (A courtesy
Dr. C. Brown, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. D. Gregg, Plum
Island Animal Disease Center and Noah’s Arkive,
College of Veterinary Medicine, The University of
. . . . ,
Veterinary Medicine, University of Illinois.)
50
Fig. 4‐43D African swine fever. Lesions in African swine
fever are similar to those observed in classical swine
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
51/105
fever, but usually much more severe. See Fig. 4‐42 for
lesions of classical swine fever. A, Epicardium and
pericardial cavity. The epicardium and subjacent
myocardium have numerous randomly distributed
of endothelial cells from infection with African swine
fever virus. Note the accumulation of a fibrinous effusion
in the pericardial cavity. B, Splenomegaly, bloody spleen. The spleen is congested with blood and riable as a result
of vascular damage caused by the virus. Lymph nodes
(not shown here) are also congested and edematous
see classical swine fever . C Endothelial cells and
lymphoid cells of white pulp of the spleen are necrotic
(e.g., pyknosis, karyolysis). H&E stain. D, Endothelial cells
lining sinusoids of the liver are necrotic (e.g., pyknosis,
aryo ys s . A so note t e necros s o some epatocytes.
H&E stain. (A courtesy Dr. C. Brown, College of
Veterinary Medicine, The University of Georgia. B
courtes Dr. D. Gre Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine, The
University of Georgia. C and D Courtesy Dr. J.F. Zachary,
College of Veterinary Medicine, University of Illinois.)
51
African Horse Sickness
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
52/105
African Horse Sickness
(Orbivirus, Nonenveloped RNA virus)
• s s m ar o ue ongue sease.
• The mechanisms of injury, endothelial cell barrier ‐,
endothelial cells.
• Characterized vascular injury cause lesions include edema, active hyperemia, petechial and ecchymotichemorrhage in different organs and tissues,
, , rhabdomyocytic necrosis.
•
The virus also infects cells of dendritic, l m hoid and monocyte‐macrophage system.
• Non‐contagious disease of horses, donkeys, and mules.
52
African Horse Sickness
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
53/105
African Horse Sickness
(Orbivirus, Nonenveloped RNA virus)
• rus en ry
– Through bite wound from midges,
– then into vessels
– or cutaneous connective tissue dendritic cells or macro ha es ma carr the virus to circulation or
regional LN, then systemic spread.
• Viral capsid proteins (VP2 and VP5) are attachment proteins that bind to glycoaminocan on the cell
membrane of target cells.
• n o e a ce s can e n ec e roug n erac on o macrop ages w ac va on o eu ocy c
adhesion cascade.
– The virus can be replicated in the endothelial cells resulting direct injury and inducing acute
inflammatory response
– Vascular lesions are probably lytic, and characterized by endothelial swelling, degeneration and
necrosis
– Vasculitis can be occurred after hemorrhage and edema affect the lung (and several organs) and
vascular thrombosis leadin to tissue infarction.• Necrosis of rhabdomyocyrtes in the heart
– Release of endogenous catecholamines
– Microthrombosis of myocardial capillaries likely resulting in myocyte ischemia
• NS3, a viral protein inserted in the host cell membrane may be cytotoxic (viroporin that alter host cell
membrane permeability.
53
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
54/105
F g. 4‐44A A r can orse s c ness. A, Pu monary e ema. T e nter o u ar septa are w e y separate an
distended with edema fluid. Edema fluid is also present in alveoli and alveolar septa. Also note the suffusivehemorrhage of the visceral pleura. These lesions are caused by infection of endothelial cells of the capillaries
of the interlobular and alveolar se ta b African horse sickness virus resultin in endothelial cell barrier
malfunction and death of endothelial cells. B, Colonic serosa, petechial and ecchymotic hemorrhages. These
lesions are also caused by infection of and damage to endothelial cells. C, Lung, interlobular edema. The
interlobular septum and alveoli contain edema fluid. Capillaries and venules are surrounded by bronchiole‐
assoc ate ymp o t ssue . sta n. , g er magn cat on o . e e n o t e a ce s o venu esare swollen, have vacuolated and reticulated cytoplasm, and large reactive nuclei consistent with responses
to injury caused by infection of these cells by African horse sickness virus, but is not pathognomonic. Note
the bronchiole‐associated l m hoid tissue BALT . A courtes Dr. D. Gre Plum Island Animal Disease
Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. R. Breeze,
Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. C and D courtesy Dr. J. F. Zachary, College of Veterinary Medicine, University of Illinois.)
54
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
55/105
F g. 4‐44B A r can orse s c ness. A, Pu monary e ema. T e nter o u ar septa are w e y separate an
distended with edema fluid. Edema fluid is also present in alveoli and alveolar septa. Also note the suffusivehemorrhage of the visceral pleura. These lesions are caused by infection of endothelial cells of the capillaries
of the interlobular and alveolar se ta b African horse sickness virus resultin in endothelial cell barrier
malfunction and death of endothelial cells. B, Colonic serosa, petechial and ecchymotic hemorrhages. These
lesions are also caused by infection of and damage to endothelial cells. C, Lung, interlobular edema. The
interlobular septum and alveoli contain edema fluid. Capillaries and venules are surrounded by bronchiole‐
assoc ate ymp o t ssue . sta n. , g er magn cat on o . e e n o t e a ce s o venu esare swollen, have vacuolated and reticulated cytoplasm, and large reactive nuclei consistent with responses
to injury caused by infection of these cells by African horse sickness virus, but is not pathognomonic. Note
the bronchiole‐associated l m hoid tissue BALT . A courtes Dr. D. Gre Plum Island Animal Disease
Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. R. Breeze,
Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. C and D courtesy Dr. J. F. Zachary, College of Veterinary Medicine, University of Illinois.
55
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
56/105
F g. 4‐44 A r can orse s c ness. A, Pu monary e ema. T e nter o u ar septa are w e y separate an
distended with edema fluid. Edema fluid is also present in alveoli and alveolar septa. Also note the suffusivehemorrhage of the visceral pleura. These lesions are caused by infection of endothelial cells of the capillaries
of the interlobular and alveolar se ta b African horse sickness virus resultin in endothelial cell barrier
malfunction and death of endothelial cells. B, Colonic serosa, petechial and ecchymotic hemorrhages. These
lesions are also caused by infection of and damage to endothelial cells. C, Lung, interlobular edema. The
interlobular septum and alveoli contain edema fluid. Capillaries and venules are surrounded by bronchiole‐
assoc ate ymp o t ssue . sta n. , g er magn cat on o . e e n o t e a ce s o venu esare swollen, have vacuolated and reticulated cytoplasm, and large reactive nuclei consistent with responses
to injury caused by infection of these cells by African horse sickness virus, but is not pathognomonic. Note
the bronchiole‐associated l m hoid tissue BALT . A courtes Dr. D. Gre Plum Island Animal Disease
Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. R. Breeze,
Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. C and D courtesy Dr. J. F. Zachary, College of Veterinary Medicine, University of Illinois.)
56
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
57/105
Fig. 4‐44D African horse sickness. A, Pulmonary edema. The interlobular septa are widely separated and
distended with edema fluid. Edema fluid is also present in alveoli and alveolar septa. Also note the suffusivehemorrhage of the visceral pleura. These lesions are caused by infection of endothelial cells of the capillaries
of the interlobular and alveolar se ta b African horse sickness virus resultin in endothelial cell barrier
malfunction and death of endothelial cells. B, Colonic serosa, petechial and ecchymotic hemorrhages. These
lesions are also caused by infection of and damage to endothelial cells. C, Lung, interlobular edema. The
interlobular septum and alveoli contain edema fluid. Capillaries and venules are surrounded by bronchiole‐
associated lymphoid tissue BALT . H&E stain. D, Higher magni ication o C. The endothelial cells o venulesare swollen, have vacuolated and reticulated cytoplasm, and large reactive nuclei consistent with responses
to injury caused by infection of these cells by African horse sickness virus, but is not pathognomonic. Note
the bronchiole‐associated l m hoid tissue BALT . A courtes Dr. D. Gre Plum Island Animal Disease
Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. B courtesy Dr. R. Breeze,
Plum Island Animal Disease Center and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. C and D courtesy Dr. J. F. Zachary, College of Veterinary Medicine, University of Illinois.)
57
Equine Polioencephalitis‐Polioencephalomyelitis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
58/105
Equine Polioencephalitis Polioencephalomyelitis
(Alphavirus, Enveloped RNA virus)
, .
• Lesions: active hyperemia, vasculitis, hemorrhage, and yellow‐white‐gray area of necrosis in gray matter of the nervous system, especially in spinal
.• A group of three disease (arbovirus …),
– Eastern equine encephalomyelitis,
– ,
–
Venezuelan equine encephalomyelitis. – St. Louis encephalomyelitis is the human counted part disease.
• V ra entry, mosqu toes tes
– Free virus and cell associated virus (macrophage or dendritic cell engulfed), regional and systemic spread
– Cause necros s n t e mye o ce s n one marrow an ymp ocytes in lymph nodes and spleen.
• Mechanism of CNS injury is undetermined
58
Equine Polioencephalitis‐Polioencephalomyelitis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
59/105
Equine Polioencephalitis Polioencephalomyelitis
(Alphavirus, Enveloped RNA virus)
• ra enve ope con a ns wo mem rane‐anc ore glycoprotein, E1 and E2
–
Attachment protein E2 – Fusion protein E1 is used to enter cell through endocytosis
• Proinflammatory cytokine, such as IFN‐r and anti‐ , ‐
lymphocytes, making it more susceptible to infection• Osteoblast provides viral replication in Eastern equine
encephalomyelitis.
Polioencephalitis‐Polioencephalomyelitis (Flavirus, enveloped virus) are similar to previous one.
59
Fig. 4‐45 Mechanism of
arbovirus and West Nile virus
infections M/O Macrophage;
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
60/105
infections. M/O, Macrophage;
NK, natural killer cell. (From
Goering R, Dockrell H, Roitt I, et
al: Mims’
medical
microbiology,
ed 4, St. Louis, 2008, Mosby.)
60
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
61/105
.
,
, spinal cord, horse. A, Brain, transverse section at the level of the hippocampus, horse. The gray matter
of the brainstem has dark red‐to‐black discoloration as a result of congestion and hemorrhage. The lesion is the result of viral infection, which has an affinity for neurons; this virus also causes vascular necrosis followed by thrombosis, but this is not common. B, Spinal cord, horse. Note the red‐to‐brown
sco orat on o t e gray matter n t e orsa an ventra orns cause y congest on an emorr age . The lesion is the result of viral infection that has an affinity for neurons; however, this virus can also
cause vascular necrosis followed by thrombosis. (Courtesy College of Veterinary Medicine, University of Florida; and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia.) 61
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
62/105
POX
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
63/105
cowpox r opoxv rus , s eeppox an goa pox apr pox ,
Swinepox[Suipox], Enveloped DNA virus)
• Loca , reg ona , an system c sprea ng us ng monocyte an macrop age system or
cell‐free virus in sheep and goat pox
• In skin, virus spreads from migrating macrophages and lymphocytes and infects
and replicates in endothelial cells, resulting to direct injury and acute
inflammatory response.
• Endothelial injury accompanied by vascular dilation, active hyperemia and acute
inflammation==macules and papules
• Langerhan’s cells are close contact with endothelial cells in Malpighian layer
(epidermal) of the skin,
– the virus may come from endothelial cells or trafficking leukocytes and infect
Langerhan’s cells,
–
then s read virus to conti uous skin e ithelial cells of stratum basale and spinosum.
– Epidermal cells death, forming vesicle with edema and cell debris,
– ,
– scar formation after immune response which resolve the viral infection63
POX
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
64/105
cowpox r opoxv rus , s eeppox an goa pox apr pox ,
Swinepox[Suipox], Enveloped DNA virus)
• Pneumonia (systemic infection),
–
lesions are variable sized and randoml distributes pock lesions in the form of large irregularly shaped
lobular area of consolidation.
– hematogenous spread via leukocytes trafficking in
‐
endothelial cells and then to bronchiolar and
– cause cell death and acute inflammation
64
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
65/105
Fig. 17‐31 Schematic diagram of the development of a poxvirus lesion over time. A, Ballooning degeneration. B,
. . ,Congestion, edema, margination, and migration of leukocytes (black dots) form the macule stage. D, Continued epidermal reticular degeneration, epidermal hyperplasia (acanthosis), dermal edema, and perivascular inflammation form the papule stage. E, The vesicle stage develops by coalescing of areas of reticular degeneration (disruption of swollen keratinocytes). F, Inflammatory cells migrate from the dermal vessels into the vesicle and accumulate in the vesicle to form the ustule sta e. G The e idermis be ins to roliferate and becomes more acanthotic and the old pustule is moved toward the epidermal surface. H, Epidermal hyperplasia progresses with the formation of elongated epidermal dermal interdigitations, and the old pustule ruptures to form a crust. Larger pustules can be umbilicated,
involve the dermis, and result in scarring. (Redrawn from Dr. Ann M. Hargis, DermatoDiagnostics; and Dr. Pamela E. Ginn, College of Veterinary Medicine, University of Florida.) 65
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
66/105
Fig. 17‐42A Capripoxvirus, skin, lamb. A, The clinical lesions are multifocal coalescing
macu es and p aques t at are indurated, emorr agic, and necrotic i e y a resu t o vasculitis. B, Note necrosis of vessel wall with fibrin deposition, red blood cells, and neutrophils and lymphocytes in the bordering dermis (vasculitis) (arrow). H&E stain. (A courtesy of Foreign animal diseases, ed 7, 2008, United States Animal Health Association. B courtesy Dr. A.M. Hargis, DermatoDiagnostics. Photographed from slides provided by Division of Animal Medicine, Animal Technology Institute Taiwan.
From AFIP WSC October 8, 2008, Conference 5, Case III.) 66
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
67/105
Fig. 17‐44A Swinepox, skin, piglet. A, Note the four umbilicated pustules in the abdominal skin. B, Note keratinoc tes with balloonin de eneration and eosino hilic cytoplasmic inclusion bodies (arrowheads). Ballooning degeneration develops before vesicle formation. H&E stain. (Acourtesy Dr. M.D. McGavin, College of Veterinary Medicine,
n vers y o ennessee. cour esy r. . . arg s, Dermato‐Diagnostics. Photographed from slides provided by Department of Veterinary Pathology, Western College of Veterinar Medicine Universit of Saskatchewan. From AFIP WSC January 21, 1998, Conference 15, Case IV.)
67
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
68/105
Fig.
4‐
46A Sheeppox and
goatpox.
A, Skin, teats, inguinal area. Macules, papules, vesicles, crusts (scabs), and papillomas (epidermal hyperplasia) are present on the skin of the inguinal area and teats. Additional
‐
in Fig. 17‐31 and macroscopically and microscopically in Figs. 17‐42 (sheeppox) and 17‐44 (swinepox). B,
Lung, pox lesions. These circumferentially expanding dark red to plum‐colored lesions of varied sizes are
areas of proliferating bronchial and bronchiolar mucosal epithelial cells, necrotic epithelial cells, cell debris,
and inflammation demonstrated in C. C, Lung, bronchiole. There is proliferation of mucosal epithelial cells of
the lung’s conductive system that are infected with poxvirus. Note the mononuclear inflammatory likely
bronchiole‐associated lymphoid tissue (BALT) in adjacent supporting stroma. Inset, Higher magnification of C.
’. . . , ,
Veterinary Medicine, The University of Georgia. B courtesy Dr. R. Breeze, Plum Island Animal Disease Center
and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. C courtesy Dr. J. F. Zachary, College of Veterinary Medicine, University of Illinois.)
68
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
69/105
Fig. 4‐46B Sheeppox and goatpox. A, Skin, teats, inguinal area. Macules, papules, vesicles, crusts (scabs),
and papillomas (epidermal hyperplasia) are present on the skin of the inguinal area and teats. Additional
information about the develo ment and ro ression of ox virus‐induced lesions is schematicall illustrated
in Fig. 17‐31 and macroscopically and microscopically in Figs. 17‐42 (sheeppox) and 17‐44 (swinepox). B,
Lung, pox lesions. These circumferentially expanding dark red to plum‐colored lesions of varied sizes are
areas of proliferating bronchial and bronchiolar mucosal epithelial cells, necrotic epithelial cells, cell debris,
an n ammat on emonstrate n .
, ung, ronc o e. ere s pro erat on o mucosa ep t e a ce s o the lung’s conductive system that are infected with poxvirus. Note the mononuclear inflammatory likely
bronchiole‐associated lymphoid tissue (BALT) in adjacent supporting stroma. Inset, Higher magnification of C.
H&E stain. A courtes Dr. D. Gre Plum Island Animal Disease Center and Noah’s Arkive Colle e of
Veterinary Medicine, The University of Georgia. B courtesy Dr. R. Breeze, Plum Island Animal Disease Center
and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. C courtesy Dr. J. F. Zachary, College of Veterinary Medicine, University of Illinois.) 69
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
70/105
Fig. 4‐46C Sheeppox and goatpox. A, Skin, teats, inguinal area. Macules, papules, vesicles, crusts (scabs),
and papillomas (epidermal hyperplasia) are present on the skin of the inguinal area and teats. Additional
information about the development and progression of pox virus‐induced lesions is schematically illustrated
in Fig. 17‐31 and macroscopically and microscopically in Figs. 17‐42 (sheeppox) and 17‐44 (swinepox). B,
Lung, pox lesions. These circumferentially expanding dark red to plum‐colored lesions of varied sizes are
areas of proliferating bronchial and bronchiolar mucosal epithelial cells, necrotic epithelial cells, cell debris,
.
, , . the lung’s conductive system that are infected with poxvirus. Note the mononuclear inflammatory likely
bronchiole‐associated lymphoid tissue (BALT) in adjacent supporting stroma. Inset, Higher magnification of C.
H&E stain. (A courtesy Dr. D. Gregg, Plum Island Animal Disease Center and Noah’s Arkive, College of
Veterinary Medicine, The University of Georgia. B courtesy Dr. R. Breeze, Plum Island Animal Disease Center
and Noah’s Arkive, College of Veterinary Medicine, The University of Georgia. C courtesy Dr. J. F. Zachary,
College of Veterinary Medicine, University of Illinois.) 70
POXcowpox r opoxv rus s eeppox an goa pox apr pox
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
71/105
cowpox r opoxv rus , s eeppox an goa pox apr pox ,
Swinepox[Suipox], Enveloped DNA virus)
• Reservoir
– Wild rodents
– Cats
• Indirect mechanism, hunting rodents and infect through skin
• Direct mechanism, inhalation and systemic spread
• Attachment protein to glycoaminoglycan
recep or pro e n on e arge a un an published paper).
71
Cryptosporidiosis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
72/105
(Cryptosporidia parvum)• Mechanism of injuries: dysfunction of microvillus of the brush
border, cytolysis after being released from infected cells,
.
• Lesion: no lesions grossly; microscopically, necrosis of
, .
• Viral entry
–
– Ingestion, contaminated water and food
•
• Oocysts interact with gastric acids, pancreatic enzyme, bile
72
Cryptosporidiosis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
73/105
(Cryptosporidia parvum)• Oocysts==sporozoites in ecte epit e ia rus or er microv i wit
glycocalyx) covering tips and sides of microvilli.
–
S orozoites bindin enteroc tes throu h CSL cr tos oridia arvumsporozoites ligand) like sporozoite‐specific lectin adherence factor,
GP9000, adhere to brush border of microvilli
–
communicate with feeding organells• Differentiate into trophozoites==
– asexual multiplication=schizont
– Sexual multiplication==gamatozon, Micogamont or macrogamont
• m crogamonts—m crogamates enter nto macrogamonts. ert ze macrogamates inside macrogamont, formation of oocysts,
– reinfection
– or pass through feces
73
Cryptosporidiosis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
74/105
(Cryptosporidia parvum)• A itiona ce eat , vi ous atrop y, amp i y severity o t e injury
– Parasite invasion, multiplication and extrusion
–
molecules from T lymphocytes and macrophages mediated
inflammation.
– Increase interce u ar permea i ity, a ter secretory unction, impair
absorption of villous enterocytes• Diarrhea
– Osmotic diarrhea (malabsorption), dysfunction of digestive enzyme
function in brush border
• a ure to gest car o y rates, mpa r y ro ys s, acter a fermentation, osmotic diarrhea
– Secretary diarrhea, Increase intercellular permeability from
inflammation
– Enterotoxin? 74
Cryptosporidiosis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
75/105
(Cryptosporidia parvum)
• Flattened squamous like cells
– , – Stretched over the base membrane
– Early in the reparative process
–
75
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
76/105
76
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
77/105
77
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
78/105
78
EM examination of
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
79/105
cryptosporidiosis
79
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
80/105
80
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
81/105
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
82/105
Fig. 4‐47 Life
cycle
of
Coccidioides immitis and
other
dimorphic
fungi. 82
Candidiasis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
83/105
(Candida albicans)• T e mec an sms o n ury: srupt on an eat o ce s n mucosa cause y
inflammation and the concurrent proliferation and invasion of filamentous
pseudohyphae and hyphae.
• Have two forms:
– yeast (commensal)
– filamentous pseudohyphae and hyphae (pathogenic)
• Lesions: acute pseudomembranous glossitis with extensive white to yellow
pseudomembrane consisting of desquamated epithelial cells, fibrin, and fungal
h hae over the dorsal surface of the ton ue.
• Viral entry: ingestion
– Yeast form as commensal
– gan s: componen o yeas nc u es mannose, recep or, manopro e ns.
– Mucosa receptors: fibrinogen, fibronectin, thrombin, collagen, laminin, and
vitronectin‐binding protein
– Balance between commensalism and disease
83
Candidiasis
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
84/105
(Candida albicans)• Morp o ogic p enotypic switc es: yeast to pat ogenic i amentous
hyphae or pseudohyphae.
–
Inducible chromosomal rearran ements in the enome of east in response to change in mucosal environment. Switching is irreversible.
– 25oC Vs. 37oC
– Mucosa injury, rea own
– Excessive use of broad‐spectrum antibiotics and corticosteroids,
h er l cemia,
– tissue damage secondary to chemotherapy or radiation, or
immunosuppression
– usta n o nnate an a apt ve mmun ty
• Pseudohyphae and hyphae of the filamentous phase express new
adhesion ligands, secret hydrolytic aspartyl proteinase that injury the
mucosa and invade the mucosa and submucosa (new adhesion molecules)
• Groups of virulent determinates involved in the process. 84
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
85/105
Fig. 7‐29 Thrush, tongue, foal. A pseudomembrane of hyphae of candida is present on the dorsal surface. It has been
scraped off the rostral end of the tongue (top) to reveal normal mucosa beneath the fungal mat. (Courtesy Dr. H. Gelber Colle e of Veterinar Medicine Ore on State University.)
85
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
86/105
Fig. 7‐28 Thrush (oral candidiasis), tongue, foal. A, Hyphae of Candida albicans are growing in the superficial keratin of
the tongue. H&E stain. B, Same specimen as A. Gomori’smethenamine silver stain. (Courtesy Dr. J.F. Zachary, College of Veterinar Medicine Universit of Illinois.
86
Cryptococcosis
( )
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
87/105
(Cryptococcus
neoformans)• Mec anism o injury
– Cell death likely caused by atrophy secondary to tissue distortion and compression from
expanding cryptococcal cysts in brain parenchyma. There is little or no inflammation in
s sease.
• Life cycle of the dimorphic fungus
– Mycelial (basidiospores) phase occurs in extracellular environment (25oC)
– Yeast phase, intracellularly within cell of monocyte‐macrophage system (37oC)
• Lesions: formation of expansile cystic space filled with a gelatinous matrix ca sule within the brain and s inal cord leadin to com ression and
distortion of the tissue.
• Viral entry
–
n a at on, amentous or yeast orm . ‐ um can reac to ower resp ratory tract an alveoli.
– Basidiospores deposit on the mucosa, readily be phagocytosed and killed by neutrophils
.
87
Cryptococcosis
( f )
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
88/105
(Cryptococcus
neoformans)• For surviva
– Basidiospores quickly germinate in mucosa or in phagosome to yeasts
– Yeast‐derived glycosylceramide synthase is essential for survival in mucosa but not in
phagocytes (?)
– Phospholipase. Injure alveolar macrophage, hinder the production and function of
surfatant, enhancing adhesion to pneumocyte and reduced being phagocytosed.
– L gan ‐receptor spec c s ou present ut mo ecu es not e ng ent e .
– Polysaccharide capsule of yeast present anti‐phagocytic and immunosuppressive
capability.
– e egree o encapsu a on prov e e res s ance o e p agocy ose an e
• Negative charges of capsules
– Inhibit phagocytosis and killing
– Cause complement depletion
– Antibody un‐responsive
– Dys‐regulation of cytokine secretion
– Inhibit recognition of yeast by chemotaxis of leukocytes from the blood stream, results
in the lacing of inflammation in cyst.
88
Cryptococcosis
(C f )
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
89/105
(Cryptococcus
neoformans)• A ter p agocytos s an p agosome‐ ysosome us on
– Yeast synthesizes additional polysaccharide capsule within the phagolysosome
of the macrophage
– Dilute lysosome hydrolase and other toxic content
– Physical barrier
–
lesions)
• Components of capsule also suppress the immune system
– , ,
small quanity of mannoprotein.
• Brain lesions
– Direct expansion into meninges and neuropile from nasal route – Leukocyte trafflicking
• Endothelial infection in brain
• Release of death fungus from dead macrophage
• Dead macrophage associate immune mediation 89
Cryptococcosis
(C t f )
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
90/105
(Cryptococcus
neoformans)
• Melanin
–
– Anti‐oxidant and eliminates reactive oxygen
species
– Use do amine nor‐e ine hrine
epinephrine as substrate for melanin
90
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
91/105
Fig. 14‐49 Cryptococcosis, thalamus, cerebellum, and mesencephalon, transverse “ ”, .
(arrows). Although the lesions look like cavities, they are filled with organisms, and the faint gray appearance is caused by the mucinous capsules of numerous cryptococci. Cryptococcus
neoformans usually induces a granulomatous inflammation in most , , ,
absent. (Courtesy Dr. M.D. McGavin, College of Veterinary Medicine, University of Tennessee.)
91
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
92/105
Fi . 14‐50A Le tomenin eal cr tococcosis. A The thick unstained mucinous ca sule
surrounding the organism results in the formation of a clear space (halo) in H&E stained sections (arrow). This feature is useful in identifying the organism in cytologicpreparations and tissue sections. Also see Fig. 14‐48, B. H&E stain. B, The mucinous
, method to identify the organism (arrow). Mayer’s mucicarmine stain. (Courtesy Dr. J.F. Zachary, College of Veterinary Medicine, University of Illinois.)
92
Prion Diseases
(Transmissible spongiform encephalopathies)
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
93/105
(Transmissible spongiform encephalopathies)e mec an sms o n ury: me a o c ys unc on o neurons an
neural cells caused by the conversion of normal cellular prionprotein (Prpc) to an abnormal form (Prpsc) and the accumulation of
sc .
• Lesions: brain atrophy may occur in the chronic cases grossly. Microscopically, vacuolation in neurons (spongiform change),
, , .
• Disease: scrapie (sheep), BSE, chronic wasting disease (CWD) in deer and elk, transmissible mink encephalopathy, feline spongiform
, .
• Source and origin of prion protein is undetermined.
• Transmission:
– Ingestion• Offal (waste or carcass from infected animal
– Inhalation or direct contact
93
Prion Diseases
(Transmissible spongiform encephalopathies)
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
94/105
(Transmissible spongiform encephalopathies) : , ,
• Prion can attach to apical surface of mucosal epithelial cells, M cells and dendritic cells, in tonsillar, alimentary, and respiratory mucosa,
.• Transcytosis, or dendritic cell migration, (or macrophage migration) may
provide prion to pass the epithelial cells or M cells, to their basolaterialsurface and to ain access to infect B and T cells macro ha e and dendritic cells in the GALT or BALT
•
Follicular dendritic cells and B cells are the primary site of replication, then spread systemic through leukocyte trafficking
• Prion are able to infect nerve ending of vagus nerve, sympathethic nerve and sensory nerve ; and use retrograde axonal transport to gain access to CNS and spread in nervous system via synaptically‐linked neuron
• In macrop age an en r t c ce s, pr on are ocate n mu t ves cu arendosomes and may be transferred between cells in exosomes. It may be
the way in the inter‐nuronal spread within the nervous system.
94
Prion Diseases
(Transmissible spongiform encephalopathies)
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
95/105
(Transmissible spongiform encephalopathies)• Cell receptor or ligand: undetermined
• Most cells have Prpc . The highest concentration are present in
e nervous sys em, espec a y n synap c mem rane as a
neuronal membrane glycoprotein. Prpc is also expressed in
.
•
Function of Prp
c
is unknown but its physiologic function may include immunore ulation si nal transduction co er
binding, synaptic transmission, induction of apoptosis, or
protection against apoptosis.
• In neuron, Prpsc serves as translation template that converts
(conformational change) normal Prpc to Prpsc , Prpsc a
m s o e a aggregate ‐s eet‐r c so orm o rp
95
Prion Diseases
(Transmissible spongiform encephalopathies)
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
96/105
(Transmissible spongiform encephalopathies)• This folding pattern makes Prpsc resistant to the action of
protease and cause it to aggregate and accumulate as an
and fibrous plaque.
• sc
however,
– reduced antioxidant rotection
– increased oxidative stress,
– lost normal Pr c function
– or toxicity caused by Prpsc
96
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
97/105
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
98/105
98
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
99/105
Fig. 4‐48 How prions injure cells. 1,
Normal cells express cellular prion
protein (PrPc) at the cell membrane as
linear proteins. 2, Abnormal form
(PrPSc) exists as a free globular
glycoprotein, which can interact with
PrPc. 3, PrPc is released from the cell
mem rane and is converted into PrP c.
4, Cells produce more PrPc and the
cycle is repeated. 5, PrPSc
accumu a es as p aques an s internalized by cells. (From Goering R,
Dockrell H, Roitt I, et al: Mims’
, , . ,
2008, Mosby.)
99
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
100/105
100
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
101/105
Fig. 4‐49 Pathogenesis of transmissible spongiform encephalopathies. Prions appear to use M cells
(also macrophages) to enter Peyer’s patches and infect dendritic cells as well as macrophages and
lymphocytes. Dendritic cells (and likely macrophages) then spread prions through leukocyte trafficking in lymphatic vessels to local, regional, and systemic lymphoid nodules, lymph nodes, and/or spleen where
infection is sustained and amplified, especially in follicular dendritic cells (FDC) of the spleen and B
. ,
and by retrograde and anterograde nerve transport they spread throughout the CNS. It has been
hypothesized that prions may also spread to the CNS hematogenously, but the existence of this route is
uncertain.101
Histological features of TSE
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
102/105
Histological features of TSE
Scrapiekuru
vCJD
BSECJD
102
Histopathology of BSE
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
103/105
Histopathology of BSE
103
Li ht and electron microsco ic
findings of BSE and CJD
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
104/105
findings of BSE and CJD
104
-
8/19/2019 Viral Diseases - Mechanisms of Microbial Infections
105/105
• Pathogenesis study
– CSFV viro orin 2012 JV
– Interaction of PCV2 and PRRSV
105