Retroviridae Flashcards
Retroviruses
- Genetic info maintained in an RNA molecule
- converts RNA to DNA
Subfamily: Orthoretrovirinae
Alpharetrovirus
Avian leukosis/sarcoma complex
Subfamily: Orthoretrovirinae
Betaretrovirus
ovine pulmonary adenomatosis (Jaagsiekte)
Subfamily: Orthoretrovirinae
Gammaretrovirus
Feline leukemia virus (FeLV)
Subfamily: Orthoretrovirinae
Deltaretrovirus
Bovine leukosis virus (BLV)
Subfamily: Orthoretrovirinae
Lentivirus
Caprine arthritis encephalitis
equine infectios anemia
bovine immunodeficiency
feline immunodeficiency
maedi-visna
Subfamily: Orthoretrovirinae
Epsilonretrovirus
Walleye dermal sarcoma
Subfamily: Spumaretrovirinae
Bovine-feline -‘foamy’
Retroviruses
- Diploid genome: two copies of ss-positive-sense RNA
- Reverse transcriptase produces DNA intermediates from genomic RNA
- viral genome integrates into cell genome using integrase
- can activate or inactivate host genes
- RNA-dependent DNA polymerase replicates viral genome
- Enveloped viruses released by budding from cells membranes
Feline Leukemia virus
- naturally occurring exogenous gammaretrovirus enzootic in domestic and wild cats
- Infection is life-long
- malignant and proliferative
- opportunistic infections and anemia common: gingivitis/ulcers
- Infection prevalence usualy <2%
- can be up to 30%
- More common in catteries/multi-cat household
- Also in outdoor cats
- kittens more susceptible
Feline leukemia virus (FeLV)
Transmission
-
Horizontal-most important route
- outddor cats
- older cats
- male cats (saliva infective)
- kittens more susceptible (nursing and grooming)
- Vertical
- transplacentally
Feline leukemia virus
Pathogenesis
- Initial replication in oral/pharyngeal lymphoid tissue
- then systemic spread via lymphocytes, monocytes, macrophages
- Progressive infection
- heavy virus replication in lymphoid tissue, bone marrow, mucosal and glandular epithelial tissues
- Exposed cats seldome escape infection
- Genomic changes may result in higher replication/inc virulence
Feline leukemia virus
Diversity
- Infection usually involved genetically distinct/antigenically related exogenous FeLVs
- Virus diversity thru mutations/recombination
- Virulent traits located in LTR and SU glycoprotein
- minimal changes in SU glycoprotein can dramatically alter receptor use and disease
FeLV sub-groups based on SU glycoprotein
pathogenic determinants
- FeLV-A
- minimally pathogenic unless recombined or mutated
- FeLV-B
- recombinants of FeLV-A (SU) and related endogenous viruses
- linked to thymus lymphosarcoma and lymphoid tumors
- FeLV-C
- recombinants of FeLV-A and related endogenous virsues
- associated with severe aplastic anemia
Clinical signs associated with FeLV infection
- uneven pupils (anisocoria)
- uveitis
- enlarged lymph nodes
- chronic wounds and infections (cutaneous lesions/abcesses)

FeLV
Pathologies associated with FeLV infection
- Feline lymphosarcomas or lymphomas
- Myeloproliferative dz and anemia
- Immunopathologic dz => immune-complex mediated/immunodeficiency
- Fibrosarcoma => induced by replication defective feline sarcoma virus
FeLV-associated lymphosarcomas
- Incidence of lymphosarcomas declined
- Multicentric => tumors in lympoid and non-lymphoid tissues
- Thymic => mostly kittens
- Alimentary
- usually older cats
- GI/ Mesenteric lymtph nodes
- Unclassified
- non lymphoid tissue
- Skin, eyes, CNS
FeLV-associated myeloproliferative dz and anemia
- Erythremic myelosis => erythroid progenitor cell
- Granulocytic leukemia => granulocytic myeloid progenitor cell
- Erythroleukemia => erythroid and granulocytic myeloid precursors
- Myelofibrosis => proliferation of fibroblasts
FeLV-associated immunopathologic dz
- Immune-complex mediated
- presistently high FeLV antigen-antibody complexes produce glomerulonephritis
- lymphocyte depletion by antibody-mediated cytotoxicity against FOCMA on lymphocyte membrane
- Immunodeficiency
- chronic stomatitis
- gingivitis
- non-healing skin lesions
- subcutaneous abscesses
- CRD
- FIP
- infertility
- fetal deaths
- abortion
Feline leukemia virus
Dx
- Antigen detection
- kits based on p27 (group specific antigen)
- p27 found in progressively infected cats
- some infected cats may not have detectible intigen in blood at time of test
- Immunofluorescence takes an expert
- RT-PCR
- detects FeLV provirus as evidence of infection
- vaccination doesn’t interfere with antigen tests (unless sampled immediately after vaccination)

- FeLV-associated lymphoma of mediastinal lymph node
- normal architecture of Lymph node is gone
Feline leukemia
Immunity, prevention, control
- test and secregate infected cats
- vaccine may protect against progressive infection and dz
-
does not prevent against infection
- Don’t induce cell-mediated immunity
- vaccines w/adjuvants may induce granulomas
- recombinant canarypox doesn’t contain adjuvants
- expresses env and gag FeLV antigens
- vaccinate at 9 weeks, re-vaccinate 3 weeks later, then annually
FeLV and lymphosarcomas
- Development associated with at least 6 conserved cellular integration sites
- dysregulation of cellular oncogenes controlling cell division
- c-myc and v-myc in transformed lymphocytes
Ovine pulmonary adenomatosis
Jaagsiekte sheep retrovirus-JSRV
- adults sheep dz
- wasting and resp distress
- orig S. Africa => now worldwide
- not in Australia/New Zealand
- eradicated from Iceland
- Reportable in some US states
- may be resp for 25% annual sheep mortality in Peru
- Caused by type D retrovirus: betaretrovirus
Ovine pulmonary adenomatosis
Clinical features
- Long incubation period
- severe losses seen in sheep > / = 2 yrs old
- Progressive dyspnea, anorexia, cacexia
- Resp failure (death from blockage small airways/anoxia)
- lots of fluid in lungs (drown sheep)
-
type II pneumocytes (epithelial cells)
- disseminated in neoplastic nodules responsible for secreting the extra fluid
- fluid from nostrils when head lowered
Ovine pulmonary adenomatosis
Transmission/pathogenesis
- aerosolized lung fluids/close contact
- transforms differentiated lung epithelial (pneumocytes type II) in terminal airways
- bronchioles and alveoli
- Proviral DNA in pneumocytes II, lymph tissue, alveolar macrophages, PBLs
- Active replication probably restricted to bronchoalveolar epithelial cells
- Sheep don’t develop antibodies… (no test)
Introduction of Jaagsiekte
- Usually by introducing infected sheep to flock (Rams)
- Facilitated by close contact houseing
Ovine pulmonary adenomatosis
Patohlogy
- Nodular lesions in lung at slaughter/necropsy
- Microscopic pathology indicates epithelial proliferation in bronchioles and alveoli
- Tumors correspond to adenoma or adenocarcinoma
- Metastes
- not common
- can occur to regional/pulmonary lymph nodes
Ovine pulmonary adenomatosis
Gross review lungs
- Won’t deflate
- mottled with coalescing to diffuse proliferative areas (pale pink) with red areas (atelectasis)
- Large, firm, gray coalescing proliferative and fibrotic masses
Ovine pulmonary adenomatosis
DIagnosis
(21:58)
- Lack of antibody response
- immunological tolerance triggered by closely related endogenous retroviruses
-
Clinical Signs
- too late
- Detection in colostrum/milk
- Virus isolation….?