4. Blood-borne, urogenital, sexual transmission Different routes Important factor in common: secretions/tissues from infected individual come into contact with mucus membranes of uninfected individual Minimum environmental exposure for virus Many examples-behavior is primary ecological factor

The unusual case of Hepatitis Viruses Viral hepatitis 2 types recognized “infectious” aka Type A (HAV) “serum” aka Type B (HBV) Tests available for HBV in the 1970s, reveal NANB hepatitis, agent identified in 1989 (HCV) Hepatitis delta agent (HDV) 1983 Hepatitis E, 1983, GI virus, (HEV) Hepatitis F, 1994, (HFV) ?????? Hepatitis G, 1995, (HGV or GBV) All of these viruses are hepatotropic!!!

Hepatitis virus families Family or genus HAV Picornaviridae HBV Hepadnaviridae HCV Flaviviridae HDV Deltavirus HEV Caliciviridae HFV ??? HGV

Transmission of Hepatitis Viruses HAV, HEV: contaminated food or water HBV, HCV, HDV, HFV, HGV: blood and blood products shared needles sexual transmission transplants (nosocomial, iatrogenic)

Replication properties of Hepatitis viruses Replication-competent HAV Yes HBV HCV HDV No, defective and dependent on HBV HEV HFV ??? HGV

Hepatitis viruses and liver complications Initial Disease Long-term disease and Liver Cancer HAV Acute - HBV ++ HCV Chronic + HDV (+HBV coinfection) ++++ HEV HFV ???? HGV

HBV vs. HDV HBV is an RNA/DNA virus that is unique among viruses. It is fully functional and often found by itself in patients. HDV is an RNA-based sub-viral pathogen that shares features with (but is not identical to) plant satellite viruses and viroids. It is never found by itself in patients.

Followup on HDV Structure

HBV-prototype hepadnavirus Extracellular form is DNA Replicates via reverse transcriptase step

Outcomes of HBV infection

HEPATITIS B VACCINE Early vaccine from killed virus-safety? No good experimental models Recombinant DNA vaccine-1980s eg- RECOMBIVAX Produced by recombinant DNA technology in yeast Seroconverts 99% healthy adults 20 to 29 years old Subunit vaccine: HBsAg Vaccine protects against active Hepatitis B, asymptomatic HBV, the carrier state, & HDV Vaccine is 90-95% effective in a wide range of population ages

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

Arbovirus classification Family Genera Example Virus Togaviridae (Type A) Alphavirus Eastern Equine Encephalitis Flaviviridae (Type B) Flavivirus Yellow Fever Bunyaviridae (Type C) Bunyavirus Bunyamwera Nairovirus Crimean-Congo Hemorrhagic Fever Phlebovirus Sicilian Sandfly Fever “Arbovirus” is jargon but widely used

Simplest transmission cycle Urban Dengue fever (Aedes spp.) Urban yellow fever (Aedes aegypti)

Dengue transmission-a more complete picture

Complex cycles are more common This example involves several vertebrate and vector species

Terms Reservoir, primary and secondary Primary host, amplifying host, natural host Primary, secondary vectors Propagative vs mechanical transmission circulative Venereal, transovarial transmission Dead-end host Zoonosis, zoonotic disease Endemic, enzootic, etc. Skunks, raccoons, bats etc. are reservoirs of rabies virus (a rhabdovirus) but not vectors.

Flaviviridae-Three Important Genera 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 Mospquito Vectors No known For some Viruses In each cluster

Yellow Fever Virus “vomito negro”, “yellow jack” Philadelphia, 1793 Haiti, 1802 New Orleans, Memphis, 1878 Panama, 1880s

YFV transmission involves multiple cycles

Yellow Fever Virus Infection Yellow fever is a viral haemorrhagic fever. Incubation period usually is 3 to 6 days. Mortality rate in severe yellow fever is 50% with death occurring 7 to 10 days after onset. Infection varies from a mild illness followed by death 2 to 3 days later to a very mild or subclinical infection. Estimated 200,000 cases worldwide and 3000 deaths annually Travellers at risk Vector transmission of yellow fever by mosquitoes was proposed by Carlos Finlay in 1881 and demonstrated Walter Reed and others 1898

The “Heroes” of Yellow Fever Research Walter Reed Jesse Lazear Max Theiler William Gorgas Developed YF vaccine transmission of YF Died in YF transmission experiments U.S. Surgeon General Broke YF transmission cycle in Cuba and Panama Theiler- YFV vaccine

But YFV is NOT a good candidate for eradication. 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.

Bunyaviridae 3 ssRNA genome segments + or – or +/- Varies w virus Envelope No matrix >300 known worldwide Many diseases

Bunyavirus Diseases and Vectors 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. 1

LaCrosse virus Now grouped with California serogroup But mainly in Eastern US Treehole (woodland) mosquito Aedes triseriatus Most common in males under 16 Approx. 90 cases per year reported Neurological sequelae

Total US cases through 2010 Most frequent Arboviral infection in US Case frequency

LaCrosse Transmission

Humans accidental hosts-dead end hosts Transovarial transmission Venereal transmission Vector transmission through blood

Vertical vs. horizontal transmission in animals Vertical transmission is from parent to offspring in some way that is related to reproduction. Trans-placental-fetal (Rubella) Maternal-parturition (Herpes simplex) Maternal-neonatal (HIV) Germ line (?)

Plant virus transmission The cell wall is a formidable barrier to viruses. Receptors? There is only one known portal of entry for plant viruses. How is it created?

Mechanical transmission of plant viruses Abrasions of leaves or stems Field transmission Laboratory transmission May require abrasive material such as carborundum

Vector transmission Arthropods-aphids, thrips, leafhoppers, whiteflies Helper component of potyviruses Nematodes (Nepoviridae, Tobraviridae)

Transmission by parasites Dodder (Cuscuta subinclusa, etc.) Fungi (e.g. Olpidium brassicae), TNV, STNV, lettuce big vein virus