4. Blood-borne, urogenital, sexual 4. Blood-borne, urogenital, sexual transmissiontransmission

Different routesDifferent routes Important factor in common: Important factor in common:

secretions/tissues from infected individual secretions/tissues from infected individual come into contact with mucus membranes come into contact with mucus membranes of uninfected individualof uninfected individual

Minimum environmental exposure for virusMinimum environmental exposure for virus Many examples-behavior is primary Many examples-behavior is primary

ecological factorecological factor

The unusual case of Hepatitis VirusesThe unusual case of Hepatitis Viruses

Viral hepatitisViral hepatitis

2 types recognized2 types recognized

““infectious” aka Type A (HAV)infectious” aka Type A (HAV)

““serum” aka Type B (HBV)serum” aka Type B (HBV) Tests available for HBV in the 1970s, reveal NANB Tests available for HBV in the 1970s, reveal NANB

hepatitis, agent identified in 1989 (HCV)hepatitis, agent identified in 1989 (HCV) Hepatitis delta agent (HDV) 1983Hepatitis delta agent (HDV) 1983 Hepatitis E, 1983, GI virus, (HEV)Hepatitis E, 1983, GI virus, (HEV) Hepatitis F, 1994, (HFV) ??????Hepatitis F, 1994, (HFV) ?????? Hepatitis G, 1995, (HGV or GBV)Hepatitis G, 1995, (HGV or GBV)

All of these viruses are hepatotropic!!! All of these viruses are hepatotropic!!!

Hepatitis virus familiesHepatitis virus families

Virus Family or genus

HAVHAV PicornaviridaePicornaviridae

HBVHBV HepadnaviridaeHepadnaviridae

HCVHCV FlaviviridaeFlaviviridae

HDVHDV DeltavirusDeltavirus

HEVHEV CaliciviridaeCaliciviridae

HFVHFV ??????

HGVHGV FlaviviridaeFlaviviridae

Transmission of Hepatitis VirusesTransmission of Hepatitis Viruses

HAV, HEV: HAV, HEV:

contaminated food or watercontaminated food or water HBV, HCV, HDV, HFV, HGV:HBV, HCV, HDV, HFV, HGV:

blood and blood productsblood and blood products

shared needlesshared needles

sexual transmission sexual transmission

transplants (nosocomial, iatrogenic)transplants (nosocomial, iatrogenic)

Replication properties of Hepatitis Replication properties of Hepatitis virusesviruses

Virus Replication-competent

HAVHAV YesYes

HBVHBV YesYes

HCVHCV YesYes

HDVHDV No, defective and dependent on HBVNo, defective and dependent on HBV

HEVHEV YesYes

HFVHFV ??????

HGVHGV YesYes

Hepatitis viruses and liver Hepatitis viruses and liver complicationscomplications

VirusVirus Initial DiseaseInitial Disease Long-term disease Long-term disease and Liver Cancerand Liver Cancer

HAVHAV AcuteAcute --

HBVHBV AcuteAcute ++++

HCVHCV ChronicChronic ++

HDV (+HBV HDV (+HBV coinfection)coinfection)

AcuteAcute ++++++++

HEVHEV AcuteAcute --

HFVHFV ???????? ????????

HGVHGV ChronicChronic ????????

HBV vs. HDVHBV vs. HDV

HBV is an RNA/DNA virus that is unique HBV is an RNA/DNA virus that is unique among viruses. It is fully functional and among viruses. It is fully functional and often found by itself in patients.often found by itself in patients.

HDV is an RNA-based sub-viral pathogen HDV is an RNA-based sub-viral pathogen that shares features with (but is not that shares features with (but is not identical to) plant satellite viruses and identical to) plant satellite viruses and viroids. It is never found by itself in viroids. It is never found by itself in patients.patients.

Followup on HDV StructureFollowup on HDV Structure

HBV-prototype hepadnavirusHBV-prototype hepadnavirus

Extracellular form is DNAExtracellular form is DNA Replicates via reverse transcriptase stepReplicates via reverse transcriptase step

Outcomes of HBV infection

HEPATITIS B VACCINE

Early vaccine from killed virus-safety?Early vaccine from killed virus-safety?

No good experimental modelsNo good experimental models

Recombinant DNA vaccine-1980sRecombinant DNA vaccine-1980s eg- eg- RECOMBIVAX RECOMBIVAX

Produced by recombinant DNA technology Produced by recombinant DNA technology in yeastin yeast

Seroconverts 99% healthy adults 20 to 29 Seroconverts 99% healthy adults 20 to 29 years oldyears old

Subunit vaccine: HBsAgSubunit vaccine: HBsAg

Vaccine protects against active Hepatitis B, Vaccine protects against active Hepatitis B, asymptomatic HBV, the carrier state, & asymptomatic HBV, the carrier state, & HDVHDV

Vaccine is 90-95% effective in a wide range Vaccine is 90-95% effective in a wide range of population agesof population ages

5. Vector transmission 5. Vector transmission Intermediate species carries virus from host to hostIntermediate species carries virus from host to host ““biological” transmissionbiological” transmission Arthropod vectors for animal virusesArthropod vectors for animal viruses Insects, ticks, etc. Insects, ticks, etc. ““Arboviruses” are Arboviruses” are ararthropod-thropod-bobornerne ““Viruses Viruses   maintained maintained   in nature principally, or in nature principally, or   to to   an an   important extent, important extent,   through through   biological biological   transmission transmission   between between     sus-ceptible vertebrate sus-ceptible vertebrate   hosts by hosts by haematophagous arthropods or through haematophagous arthropods or through   transovarian transovarian and possibly venereal transmission in arthropods.”and possibly venereal transmission in arthropods.”

Arbovirus classificationArbovirus classification

FamilyFamily GeneraGenera Example VirusExample Virus

Togaviridae (Type A)Togaviridae (Type A) AlphavirusAlphavirus Eastern Equine Eastern Equine EncephalitisEncephalitis

Flaviviridae (Type B)Flaviviridae (Type B) FlavivirusFlavivirus Yellow FeverYellow Fever

Bunyaviridae (Type C)Bunyaviridae (Type C) BunyavirusBunyavirus BunyamweraBunyamwera

NairovirusNairovirus Crimean-Congo Crimean-Congo Hemorrhagic FeverHemorrhagic Fever

PhlebovirusPhlebovirus Sicilian Sandfly FeverSicilian Sandfly Fever

“Arbovirus” is jargon but widely used

Simplest transmission cycleSimplest transmission cycle

Urban Dengue fever (Aedes spp.)Urban Dengue fever (Aedes spp.) Urban yellow fever (Aedes aegypti)Urban yellow fever (Aedes aegypti)

Dengue transmission-a more complete picture

Complex cycles are more commonComplex cycles are more common

This example involves several vertebrate and vector species

TermsTerms Reservoir, primary and secondaryReservoir, primary and secondary Primary host, amplifying host, natural hostPrimary host, amplifying host, natural host Primary, secondary vectorsPrimary, secondary vectors Propagative vs mechanical transmissionPropagative vs mechanical transmission circulativecirculative Venereal, transovarial transmissionVenereal, transovarial transmission Dead-end hostDead-end host Zoonosis, zoonotic diseaseZoonosis, zoonotic disease Endemic, enzootic, etc. Endemic, enzootic, etc. Skunks, raccoons, bats etc. are reservoirs of rabies virus Skunks, raccoons, bats etc. are reservoirs of rabies virus

(a rhabdovirus) but not vectors.(a rhabdovirus) but not vectors.

Flaviviridae-Three Important Genera

1) Flavivirus (mainly mosquito or tick vectors Central European encephalitis (TBE-W), Japanese encephalitis (JE), St. Louis encephalitis (SLE), West Nile virus (WN), Dengue (DEN), Yellow fever (YF). Symptoms include fever, encephalitis, hemorrhagic fever

2) Pestivirus (not arboviruses) Contact and Saliva transmitted. Bovine viral diarrhea (BVDV), hog cholera or classical swine fever (CSFV), very important animal diseases.

3) Hepacivirus (not arboviruses) blood borne pathogens-Hepatitis C (HCV)-liver disease and liver cancer worldwide.

Flavivirus“tree”

Tick-borne

MospquitoVectors

No known VectorsFor some VirusesIn each cluster

Yellow Fever VirusYellow Fever Virus“vomito negro”, “yellow jack”

Philadelphia, 1793

Haiti,1802

New Orleans,Memphis, 1878

Panama, 1880s

YFV transmission involves multiple cycles

Yellow Fever Virus Yellow Fever Virus InfectionInfection

Yellow fever is a viral haemorrhagic feverYellow fever is a viral haemorrhagic fever.. Incubation period usually is 3 to 6 daysIncubation period usually is 3 to 6 days.. Mortality rate in severe yellow fever is 50% with death Mortality rate in severe yellow fever is 50% with death

occurring 7 to 10 days after onsetoccurring 7 to 10 days after onset.. Infection varies from a mild illness followed by death Infection varies from a mild illness followed by death

2 to 3 days later to a very mild or subclinical infection.2 to 3 days later to a very mild or subclinical infection.

Estimated 200,000 cases Estimated 200,000 cases worldwide and 3000 worldwide and 3000 deaths annuallydeaths annually

Travellers at riskTravellers at risk Vector transmission of Vector transmission of

yellow fever by yellow fever by mosquitoes was proposed mosquitoes was proposed by Carlos Finlay in 1881 by Carlos Finlay in 1881 and demonstrated Walter and demonstrated Walter Reed and others 1898Reed and others 1898

Walter Reed

Jesse Lazear

MaxTheiler William GorgasDeveloped

YF vaccine

transmission of YF

Died in YF transmissionexperiments

U.S. Surgeon GeneralBroke YF transmission

cycle in Cuba and Panama

The “Heroes” of Yellow Fever Research

Theiler- YFV vaccine

Derivation of a Yellow Fever Virus Vaccine The original virus isolate was obtained from an African named Asibi. Passed 53 times in monkeys with intermittent periods in Aedes agyptii. Passed 18 times in minced mouse embryo tissue culture. Passed 50 times in minced whole chicken embryo tissue culture. Passed 152 times in minced chicken embryos.A marked change in virulence occurred between in vitro

passage 89 and 114. Vaccine was called 17D.The 17D vaccine has permitted health

authorities to break the cycle of yellow fever and get the disease under control in South

America and Africa.But YFV is NOT a good candidate for

eradication.

BunyaviridaeBunyaviridae

3 ssRNA genome segments3 ssRNA genome segments + or – or +/-+ or – or +/- Varies w virusVaries w virus EnvelopeEnvelope No matrixNo matrix

>300 known worldwide>300 known worldwide Many diseasesMany diseases

Genus Disease & Vector Relations

Orthobunyavirus California Encephalitis Group, others.

mosquito vectors - bird, rodent, human cycle

Hantavirus Hemorrhagic fever & renal syndrome Hantavirus pulmonary syndrome-

(rodents)

Nairovirus Crimean-Congo Hemorrhagic Fever- ticks.

Phlebovirus Rift Valley Fever, plus several rodent & bird viruses-mosquito, sandfly & tick

Tospovirus Broadest host range known (>360 plant host species-thrips.

Bunyavirus Diseases and VectorsBunyavirus Diseases and Vectors

LaCrosse virusLaCrosse virus

Now grouped with California Now grouped with California serogroup serogroup

But mainly in Eastern USBut mainly in Eastern USTreehole (woodland) Treehole (woodland)

mosquito mosquito Aedes triseriatusAedes triseriatusMost common in males Most common in males

under 16under 16Approx. 90 cases per year Approx. 90 cases per year

reportedreportedNeurological sequelaeNeurological sequelae

Total US cases through 2010

Most frequentArboviral infection in US

Case frequency

LaCrosse TransmissionLaCrosse Transmission

Humans accidental hosts-dead end hosts

Transovarial transmissionVenereal transmissionVector transmission through blood

Vertical vs. horizontal transmission Vertical vs. horizontal transmission in animalsin animals

Vertical transmission is from parent to offspring Vertical transmission is from parent to offspring in some way that is related to reproduction.in some way that is related to reproduction.

Trans-placental-fetal (Rubella)Trans-placental-fetal (Rubella) Maternal-parturition (Herpes simplex)Maternal-parturition (Herpes simplex) Maternal-neonatal (HIV)Maternal-neonatal (HIV) Germ line (?)Germ line (?)

Plant virus transmissionPlant virus transmission

The cell wall is a formidable barrier to The cell wall is a formidable barrier to viruses.viruses.

Receptors?Receptors?

There is only one known portal of entry for There is only one known portal of entry for plant viruses.plant viruses.

How is it created?How is it created?

Mechanical transmission of plant Mechanical transmission of plant virusesviruses

Abrasions of leaves Abrasions of leaves or stemsor stems

Field transmissionField transmission Laboratory Laboratory

transmissiontransmission May require abrasive May require abrasive

material such as material such as carborundumcarborundum

Vector transmissionVector transmission

Arthropods-aphids, thrips, leafhoppers, Arthropods-aphids, thrips, leafhoppers,

whiteflieswhiteflies

Helper component of potyvirusesHelper component of potyviruses

Nematodes (Nepoviridae, Tobraviridae)Nematodes (Nepoviridae, Tobraviridae)

Transmission by parasitesTransmission by parasites

Dodder (Cuscuta subinclusa, etc.)Dodder (Cuscuta subinclusa, etc.) Fungi (e.g. Olpidium brassicae), TNV, Fungi (e.g. Olpidium brassicae), TNV,

STNV, lettuce big vein virusSTNV, lettuce big vein virus