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Retroviruses October 5,6,7 2010. Retroviruses Viral RNA Viral DNA (integrated into host genome) Viral mRNA, genome Reverse (retro) transfer of genetic.

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Presentation on theme: "Retroviruses October 5,6,7 2010. Retroviruses Viral RNA Viral DNA (integrated into host genome) Viral mRNA, genome Reverse (retro) transfer of genetic."— Presentation transcript:

1 Retroviruses October 5,6,7 2010

2 Retroviruses Viral RNA Viral DNA (integrated into host genome) Viral mRNA, genome Reverse (retro) transfer of genetic information Usually, well adapted to their hosts Endogenous retroviruses

3 Retroviridae Oncovirinae Lentivirinae Spumavirinae Avian leukosis viruses Feline, bovine, human immunodeficiency viruses Equine infectious anemia virus Feline leukemiavirus “Foamy” agents

4 A retrovirus virion

5 The viral genome (oncornaviruses) LTR GAGPOLENV Long terminal repeat Group specific antigens (nucleocapsid) RNA dependant DNA polymerase Envelope proteins (type-specific antigens) All three genes - GAG, POL, ENV - required for replication

6 Replicative cycle

7 Interference

8 Pseudotypes

9 How do oncoviruses cause cancer?

10 Peyton Rouse and the cancer causing chicken virus Rockefeller University 1912

11 The Rouse sarcoma virus genome LTR GAGPOLENV SRC LTR GAGPOLENV

12 D. Stehelin, H.E. Varmus and J.M. Bishop 1976 DNA related to the transforming gene of avian sarcoma virus is present in normal avian DNA Nature 260:

13 Retroviruses and cancer

14 Other transduced oncogenes 1. Sis - platelet derived growth factor (PDGF) cDNA by wooly monkey or cat in simian sarcoma and feline sarcoma viruses Cell transformed by SSV PDGF receptor Sis protein proliferation

15 Other transduced oncogenes 2. Erb. Epidermal growth factor receptor transduced by avian erythroblastosis and fibrosarcoma causing viruses P P P EGRF receptor vErb kinase domain stim. phosp. site inhib. phos. site ligand binding site

16 Feline leukemia viruses Most common infectious cause of death in cats Cytoproliferative and cytosuppressive diseases High mortality in persistently infected cats (>80% in 3 yrs)

17 Endogenous and Type A, B, C viruses Type A Type B Type C

18 feline sarcoma and acute leukemia viruses LTR oncogene GAGPOL defective viruses that transduce cellular oncogenes

19 Pathogenesis infection by oral route infection by bite replication in tonsils replication in draining lymph node bone marrow thymusPeyer’s patches protective immune response inadequate immune response recovery latency viremia

20 Consequences of viremia cytoproliferative cytosuppressive lymphosarcomas fibrosarcomas leukemias anemia pancytopenia immunosuppression secondary infections chronic stomatitis gingivitis non-healing skin lesions respiratory infections Haemobartonella felis thymic multicentric alimentary

21 Diagnostic tests Antigen capture ELISA “FeLuke test” (p27) Fluorescent antibody test Virus neutralization PCR

22 Disease progression and diagnostic tests infection by oral route infection by bite replication in tonsils replication in draining lymph node bone marrow thymus Peyer’s patches protective immune response inadequate immune response recovery latency viremia ELISA sometimes + ELISA + FAT + epitheial cells (shedding) PCR on bone marrow

23 Prevention of FeLV infection Management Vaccines

24 Management Multi cat households or breeders –Can spread rapidly –to solve problem test isolate + cats retest –+ -> + PI –+ -> - consider - –- -> + retest 12 weeks later –to maintain test and quarantine before new introductions single cat + –retest –inform owner of consequences

25 Vaccination Inactivated virus or subunits –FeLV-A –FeLV-A, FeLV-B, FeLV-C –FOCMA Adjuvants Vectored In practical terms only FeLV-A needed Most vaccines have comparable efficacy

26 Evaluation of vaccine efficacy challenge systems “preventable fraction” factors to consider –number in study –criteria for persistent infection –method of challenge –number of controls with persistent infection

27 A,B A,B,C A,B A,B,C A,B A,B,C

28 Considerations for vaccination risk? test before vaccination vaccine site sarcomas

29 Treatment Antivirals (experimental) Immunostimulants (may not be effective)

30 Feline immunodeficiency virus (lentivirus) 1 to 5% of domestic cats infected (older male cats more likely) 5 sub-types with considerable antigenic variation May lead to AIDS like disease High rate of infection in some felids (lions, cheetahs) with no obvious sickness

31 Pathogenesis bite (virus shed in saliva) virus infects B-cells, T-cells and macrophages B-cell proliferation (swollen lymph nodes) reversed CD4:CD8 ratios immunodeficiency (opportunistic infections, B-cell lymphomas) inapparent in most cats variable time

32 Diagnostic test ELISA (antibody capture) –antibodies (most infected cats have low levels of circulating antigen) –maternal antibodies - false +ves

33 FIV vaccine

34 Cat retroviruses and endangered felids Iberian Lynx PLoS One. 2009;4(3):e4744. Epub 2009 Mar 9.

35 Equine infectious anemia virus swamp fever (equine lentivirus) Per-acute (rare) Acute/chronic Inapparent - Asymptomatic carriers CFIA - EIA page (fact sheet and stats)

36 Transmission Blood (>million viruses/ml) –Tack, instruments –Biting insects Virus in all secretions –venereal –Milk, colostrum –In utero horse fly deer fly

37 Venereal transmission

38 Tashjian, 1984, JAVMA, 184:282 Transmission by injection of semen from EIA+ and during natural breeding Transmission by injection of colostrum and natural feeding of foals (Insect transmission can not be ruled out)

39 Transmission by insects fly feeds uninterrupted virus is inactivated before next blood meal feeding is interrupted fly bites horse nearby (< 100m)

40 Pathogenesis (chronic infection) Fever and viremia antigenic change infectious phases virus multiplies in leukocytes immune complexes anemia thrombocytopenia

41 Secondary effects of thrombocytopenia petechial haemorrhages edema Slides: Hugh Townsend

42 Asymptomatic carriers infectious phase stress viremia or steroids

43 Diagnostic Tests Agar gel immunodiffusion (AGID or Coggin’s test) ELISA kit (replaced AGID, August 2008) Horse inoculation Immuno-blot cELISA

44 Coggin’s test antigen reference positive sera test samples

45 False reactions on Coggin’s test False positive –Foal with passive antibody (6 months) False negative –Recently infected horse

46 Excerpts from CFIA Disease Control Manual of Procedures, 1998 (section 7) Blood (no anticoagulants) collected by accredited vet and tested by accredited laboratory If accredited vet suspects exposure must inform District vet If sample positive, the animal, other in-contact susceptible animals and epidemiologically linked animals(30 days) re-bled and sent to The Retrovirology Centre of Expertise, PEI

47 Follow up after lab conformation of a Reactor Owner notified Premises declared infected, cold brand reactor (R) Clinical examination of all reactors and exposed animals Destruction order for animals showing clinical signs and asymptomatic reactors not isolated Compensation (up to $2,750) In contacts or animals pastured in contiguous pastures tested (30 days prior to testing) Owner’s responsibility and movement restrictions

48 Animal movement restrictions removed when: Reactor removed Remaining animals negative on tests 40 days apart –(first test after removal of reactor)

49 Conditions of isolation Must be asymptomatic Must not be used for breeding purposes Premises inspected at least 4times/yr unannounced Separated from other susceptible animals Completely fly proof, vestibuled doors Isolation notice posted on door Exercise only in enclosed fly proof arena attached to stable Exercise outside –in enclosed area –if daily high <0 o C. –No non-reactors within 200 yards All bandages, syringes etc. incinerated

50 Pregnant mares and their foals Remove foal from infected area (under license) not later than 6 months Moved to place where there are no other susceptible animals Tested after 40 days in isolation If positive(maternal antibodies) retested in 4 months If positive treat as a reactor.

51 CFIA - EIA control program CFIA - EIA page (fact sheet and stats)

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