viruses1 2
DESCRIPTION
Viruses1 2TRANSCRIPT
IntroductioIntroduction n to to
virusesviruses
Lecture topics - 1Lecture topics - 1
• What is a virus? Definition Structure and replication
• Human virus infections• Treatment
Antivirals Vaccines
Lecture topics – 2Lecture topics – 2• Immunity to viruses
Cell-mediated Humoral
• Role of Complement• Vaccination against viruses
Inactivated vaccines Live vaccines
• Interferon
Definition of a VirusDefinition of a Virus
Sub microscopic entity
consisting of a single nucleic
acid surrounded by a protein
coat and capable of
replication only within the
living cells of bacteria,
animals or plants.
Definition of a VirusDefinition of a Virus
Obligate
Intracellular
Parasite
Virion StructureVirion Structure
Nucleic Acid
Spike Projections
ProteinCapsid
Lipid Envelope
VirionAssociatedPolymerase
Virion MorphologyVirion Morphology
• Simple Structure
• Repetitive Structure
• High Level of Redundancy
Virus MorphologyVirus Morphology
Helical Icosahedral
Virus ReplicationVirus Replication1 Virus attachment
and entry
11 2 Uncoating of virion
22
3 Migration ofgenome nucleicacid to nucleus
33
4 Transcription
5 Genome replication44
55
6 Translation of virusmRNAs
66
7 Virion assembly778 Release of new
virus particles
88
Cytopathic Effect (cpe)Cytopathic Effect (cpe)Adenovirus Herpes virus
Transmission of VirusesTransmission of Viruses• Respiratory transmission
Influenza A virus• Faecal-oral transmission
Enterovirus• Blood-borne transmission
Hepatitis B virus• Sexual Transmission
HIV• Animal or insect vectors
Rabies virus
Virus Tissue TropismVirus Tissue Tropism
• Targeting of the virus to specific tissue and cell types
• Receptor Recognition CD4+ cells infected by HIV CD155 acts as the receptor for
poliovirus
In vivoIn vivo Disease Processes Disease Processes
• Cell destruction
• Virus-induced changes to gene expression
• Immunopathogenic disease
Acute Virus InfectionAcute Virus InfectionA
mou
nt
of v
iru
s
Time
Symptoms
Virus
Acute Virus InfectionsAcute Virus Infections• Localised to specific site of
body
• Development of viraemia with widespread infection of tissues
PoliovirusPoliovirus
PoliovirusPoliovirus
• Enterovirus.
• Possesses a RNA genome.
• Transmitted by the faecal oral route.
• Cause of gastrointestinal illness and poliomyelitis.
Properties of the virus
Poliovirus InfectionPoliovirus Infection
Gut
VirusInfection
Virus excretionin the faeces
Viraemia
Non-neuronaltissues
Neuronaltissues
Paralysis
Incidence of PoliomyelitisIncidence of Poliomyelitis
40
30
20
10
0
1950 1960 1970 1980
Nu
mb
er o
f ca
ses
(in
th
ousa
nd
s)
A B
Poliovirus vaccinesA: Salk – killed inactivated vaccine.B: Sabin – live attenuated vaccine
Influenza A virusInfluenza A virus
• Myxovirus• Enveloped virus with a
segmented RNA genome
• Infects a wide range of animals other than humans
• Undergoes extensive antigenic variation
• Major cause of respiratory infections
Properties of the virus
Influenza A virus InfectionInfluenza A virus Infection• Spread by respiratory route
• Virus infects cells of the respiratory tract
• Destruction of respiratory epithelium Secondary bacterial infections
• Altered cytokine expression leading to fever
e.g interleukin-1 and interferon
Spread of influenza virusSpread of influenza virus
Respiratory TractRespiratory Tract
1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999
0
100
200
300
400
500
600
Rat
e p
er 1
00 0
00 p
op
ula
tio
n
Year
Epidemic activity
Higher than expectedseasonal activity
Normal seasonal activity
Baseline activity
Weekly consultation rates for influenza and influenza-like illness: WeeklyWeekly consultation rates for influenza and influenza-like illness: WeeklyReturns Service of the Royal College of General Practitioners, 1988 to Returns Service of the Royal College of General Practitioners, 1988 to
19991999
CDR Weekly Report: 5th November 1999
Point mutation of HA and NAgenes
ANTIGENIC DRIFT
ANTIGENIC SHIFT
Genetic Reassortment
Human H3N2
Avian H3N8
Human H2N2
Generation of Novel Influenza A VirusesGeneration of Novel Influenza A Viruses
Viruses and Human TumoursViruses and Human Tumours• Epstein Barr Virus
Burkitt’s Lymphoma
• Human papillomavirus Benign warts Cervical Carcinoma
• Human T-cell Leukaemia Virus (HTLV-1) Leukaemia
• Hepatitis C virus Liver carcinoma
Virus-induced tumoursVirus-induced tumours
VirusInfection
UninfectedCell
?
[ ]Uncontrolled cell
growth and tumourformation
Virus-induced transformationVirus-induced transformation
Normal cells Transformed cells
Virus-Induced TumoursVirus-Induced Tumours
• Virus infects cell.• Virus nucleic acid, as DNA,
integrates into cellular genome.• Virus causes changes in cellular gene
expression.• Uncontrolled cell multiplication and
tumour formation.
Treatment and Prevention Treatment and Prevention of Virus Infectionsof Virus Infections
• Antivirals
• Vaccines and immunisation
Antiviral TargetsAntiviral Targets• Attachment/Entry
• Nucleic acid replication
• Virus protein processing
• Virus maturation
Problems with AntiviralsProblems with Antivirals
• Identification of virus-specific target.
• Generation of resistant variants.