1. 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

2. 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!!!

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

4. 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)

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

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

7. 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.

8. Followup on HDV Structure

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

10. Outcomes of HBV infection

11. 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

12. 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.”

13. 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

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

15. Dengue transmission-a more complete picture

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

17. 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.

18. 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.

19. Flavivirus “tree” Tick-borne Mospquito Vectors No known For some
Viruses
In each
cluster

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

21. YFV transmission involves multiple cycles

22. 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

23. 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

24. 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.

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

27. 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

28. 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

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

30. LaCrosse Transmission

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

32. 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 (?)

33. 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?

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

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

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