retroviruses Flashcards
retroviral replication
- replicate via dna intermediate
- 2x stranded dna = integrated into host dna mediated by viral integrate, from this integrated ds dna have viral replication from and production of new viral proteins and new virions released from virally infected cells
types retroviruses
- oncogenic retroviruses (alpha, death, and beta retroviruses)
- complex retroviruses (lentiviruses)
oncogenic retroviruses general featreus
tumors
important oncogenic retroviruses
- feline leukemia virus
- avian leukosis virus
- bovine leukemia virus
complex retroviruses general features
immunodeficiency
complex retroviruses important
- feline immunodeficiency virus
- equine infectious anemia virus
- ovine progressive pneumonia virus
- caprine arthritis- encephalomyelitis virus
retroviruses primarily important in who
cats
retroviruses structure
- two copies single stranded rna (pos sense)
- capsid
- envelope
- 30 copies reverse transcriptase packed into viron
retrovirus reverse transcriptase
- convert genomic rna into provirus
- released upon entry into cell
retrovirus structure
- simple retroviruses
- complex retrovirses
simple retrovirus structure
- gag, pol, env genes
gag genes encode what
group antigens (structural specific)
pol genes encode what
encode viral enzymes
env genes encode what
encode for envelope
complex retroviruses genes
additional genes that regulate replication and gene expression plus gag, pol, env
retroviruses key features
- undergo mutation and recomb
retroviruses and host genome
- integrate into host genome
- endogenous / replication defective retrovirses
- (in)activate host genes near site of integration
endogenous/ replication defective retroviruses
- live in host genome
- no replication
- no dx
- mo transmission
- can recombine with exogenous retroviruses if cell gets infected -> highly virulent sarcoma viruses
(in)activation host genes effect
- oncogenic retroviruses do this, if near tumor suppressor or oncogene can allow virus to -> tumors
retrovirus transmission
- inefficient
- not spread easily form animal to animal requires prolonged contact
oncogenic retroviruses affect who
- infect and transform cells in all classes vertebrates
- best known in cats, ruminants, chickens, and fish
oncogenic retorvirus tumor production mechanisms
- insertional mutagenesis
- capture of cell oncogene
- retroviral oncogenic gene
clinical signs oncogenic retrovirus
- depend on site of tumor
oncogenic retroviruses insertional mutagenesis
- virus integrates into host genome -> viral promotor -> infleunce expression host genes at that site ->
- if cell oncogene activation -> transofrmaiton
- if cell tumor suppression gene disruption -> loss suppressor control -> transoformation (rare)
oncogenic retrovirus tumor onset speed
very slow
oncogenic retroviruses capture of cellular oncogenes
virus captures cell oncogene and puts in own genome -> replace one of its own genes with cell oncogene -> replication defective virus bc lacking all genes needed for replication
how does replication defective virus repliacte
need to be in cell co infected with intact retrovirus (helper or replication competent virus) -> recombination -> deficient virus use enzyme from competent virus to start replicating -> sarcoma virus bc replication deficient virus has cell oncogene
oncogenic retroviruses capture cell oncogene tumor arising speed
- arise v quickly
oncogenic retroviruses cell oncogene capture nature
- rare in nature bc not transmitted bc so fatal
retroviral oncogene
- genes of certain retroviruses are themselves oncogenic
- beta and delta retroviruses, not important to vet med
feline leukemia virus virus type
- gamma retrovirus
- simple retrovurs
feline leukemia virus effects who
cat
feline leukemia virus found where how prevalent
- worldwide
- common (dec bc vac and better diagnostics)
feline leukemia virus syndromes
- tumors (lymphoma)
- leukemia
- bone marrow suppression (immunodeficiency, anemia)
most common infectious cause of death in cats
feline leukemia virus
pathogenesis feline leukemia virus
- primary oro-nasal infection -> localized virus replication in epithelium and pharyngeal lymphoid tissues -> various outcomes (depends on age, immune status, viral dose):
- abortive
- regressive
- progressive
- focal
abortive infection feline leukemia virus
- immune system kicks in -> abortive infection no viremia no dx (not abortion just not viremic)
regressive infection feline leukemia virus
- immune system does not kick in -> regressive infeciton w/ transient viremia, no dx
progressive infection feline leukemia virus
- immune system does not kick in -> progressive infection w. replication in salivary gland and urogenital mucosa -> virus sheds in saliva and urine
- persistently viremic animals, dx
focal infection feline leukemia virus
atypical
feline leukemia virus diff ages
- 100% neonatal kittens become persistently infected (90% develop tumors)
- 15-30% cats > 4 moths become persistently infected (10-15% develop tumors)
feline leukemia virus transmission
- direct contact w/ saliva of persistently infected cat (must be prolonged contact)
- vertical transmission via placenta and milk
feline leukemia virus latency
- some cured animals will be latently infected
- still have proviral dean in system
diagnostics of feline leukemia latent carriers
- if try to diagnose w/ diagnostic test will be neg unless do proviral pcr
de novo production feline sarcoma virus
- replication- deficient FeLV where cell oncogene replaces viral pol or env gene
- replication-competent (helper) FeLV infecting same cell -> recomb -> rapid transformation
feline leukemia virus related to tumors: lymphoma affect what cells
- typically T cell lineage
feline leukemia virus causes what
- bc various anatomic locations there are various clinical dx outcomes (neuro, digestive symptoms, anemia)
- feline sarcoma virus
feline leukemia virus related to immunosuppression see what signs
- gingivitis, chornic stomatitis
- poor fertility, fetal death, abortion
- immune mediated dx
feline leukemia virus diagonsis
- elisa (snap tests, detects free antigen)
- IFA
- DNA PCR
- RNA PCR (earliest detection method)
elisa feline leukemia virus detects what types
- abortive
- regressive
- progressive
ifa feline leukemia virus detects what
- detects later stage of infection
- regressive or progressive (when virus reached bone marrow)
feline leukemia virus control
- keep viremic cats away from other cats to prevent spread and protect immune-suppressed infected cat
- vac
- test catteries
differential diagnosis feline leukemia virus
- feline immunodeficiency virus
- non-viral neoplasia
- toxoplasmosis
avian leukosis virus general features
- alpha retrovirus
- simple retrovirus
avain leukosis virus found where
- world wild
- most commercial flocks exogenous virus free
avian leukosis virus dx generally
- dx rare bc development neutralizing antibodies clear infection
avian leukosis virus when cause dc
- transmission through egg or infeciton of neonatal bird if immunologically tolerant -> viremic for life -> healthy at first then source horizontal transmission in flocks and develop tumors
rous sarcoma virus
- caused by avain leukosis virus
- replication defective retrovirus w/ cell oncogene -> rapid tumor formation
avian leukosis virus horizontal transmission
- transient viremia -> neutralizing aitnody -> rare for dx to form
avain leukosis virus congenital transmission
- viremia -> tolerance -> neoplasia
avian leukosis virus clinical signs
- lymphoid leukosis (Bcell tumors spleen, liver, bursa of fabricis)
- osteoporosis (thick leg syndrome)
- renal tumors
- mesenchymal tumors
- myeloid and erythroid tumors
avian leukosis viral differential diagnosis
marek’s dx
avian leukosis virus broilers
- no v important for broilers bc due early
avian leukosis virus important for who
- flocks of layers that lay eggs for vac production
avain leukosis virus control
- most comercial flocks consist of alv- resistant cliche strains (lack correct receptors for viral entry)
- no vac
bovine leukemia virus general characteristics
- exogenous deltaretrovirus
- complex retrovirus
bovine leukemia virus effects who
cattle
bovine leukemia found where/ prevalence
- worldwide
- high prevalence
bovine leukemia virus transmission
- iatrogenic
- mechanical vectors
- ingestion of infected milk
bovine leukemia virus infects what -> what
B cells -> persistent lymphpcytosis (30%) -> +/- progress to multi centric lymphoma
-* most infections are subclinical
bovine leukemia virus diagnosis
- subclinical cases IDed by serological testing of serum or milk
bovine leukemia virus control
- test and removal programs Europe not us
- test every 3 months and eliminate pos animals -> seroneg herd 1-2 yrs bc inefficient spread in herd
lentivirus general characteristics
- chornic
- long term infections
- complex retrovirus
lentiviruses infect what leading ot what
- cd4t+ cells -> progressive immunodeficiency
- monocyte/ macrophages -> chronic inflam dx
lentivirus transmission
- v inefficient
- if infected infected for life
feline immunodeficiency virus virus type
- lentivirus (complex retrovirus)
feline immunodeficiency location and prevalence
- world wide
- common
feline immunodeficiency virus in who
- domestic and wild cats, infected w/ diff strains
feline immunodeficiency often confection with what, see what
- feline leukemia virus
- see overlap clinical syndromes of 2 viruses bc immunosuppression
feline immunodeficiency transmission
- bites
- milk and colostrum from infected queen to kittens
feline immunodeficiency virus pathogenesis
infects cd4 T cells in regional ln -> T cell associate viremia -> generalized enlargement lns and fever -> persistence for years -> immunodeficiency
- accompanied by transient or prolonged neutropenia
- drop in cd4+ T cells -> lower cd4/cd8 ratio (the lower it is the worse the prognosis)
feline immunodeficiency virus clinical signs
- overlap w/ FeLV
- gingivitis
- progressive weight loss
- persistent fever
- chronic/ recurrent infections
- anemia
feline immunodeficicy virus diagnosis
- snap test for antibodies (high rate false pos and risk false neg)
feline immunodeficiency virus tx
- avoid by keeping cats indoors
- tx symptoms
- vac low efficacy
equine infectious anemia what type virus
lentivirus (complex retrovirus)
equine infections anemia found where / how common
- world wide
- common
equine infectious anemia affects who
horses and other equids
equine infectious anemia signs
- no dx
- acute dx w/ death (< 1 month, 30%)
- lifelong persistant infection w/ flares acute dx
equine infectious anemia transmission
- mechanical (biting arthropods)
- iatrogeically
- intrauterine transmisison
equine infectious anemia pathogenesis
- lifelong cell associated viremia in peripeheral bld mononuclear cells
- mature macrophages produce most of virus
- waves of dx correspond w/ emergence new genetically variable viruses arising in host allowing allowing for immune escape
equine infectious anemia clinical assigns acute
- anemia
- blood stained feces
- petechial mucosal hemorrhages
- fatal or development of subacute infection
subacute clinical signs equine infectious anemia virus
- fever followed by recovery and lifelong infection
- horses normal or experience recurrent dx
- chronic dx- cachexia, anemia, ventral edema
equine infectious anemia virus differential diagnosis
- equine viral arteritis
equine infectious anemia diagonsis
- clincial signs
- coggins test
equine infectious anemia enzootic regions
- stable horses in insect secure facility when vectors most active
equine infectious anemia tx
- no tx no vac
- isolate or euth seropos animals
ovine progressive pneumonia virus associated with what dx in who
- dyspnea (common)
- encephalitis (rare)
- in sheep in sheep producing countries
ovine progressive pneumonia what type virus
lentivirus (complex retrovirus)
ovine progressive pneumonia clinical signs
exercise intolerant, dyspnea, cachexia, arthritis/ lameness
ovine progressive pneumonia tx
- no vac
- cull infected animals
ovine progressive pneumonia test
- elisa
- pcr
caprine arthirits- encephalomeyelitis virus found where prevalence
- worldwide
- common
caprine arthritis encephalomyeleitis transmission
- infected milk
caprine arthritis encephalomyelitis virus type
lentivirus (complex retrovirus)
caprine arthritis encephalomyeleitis pathogenesis
monocytes/ macrophages in gut -> migration infected cells into
synovial of jts -> synovitis and swollen jts (goats > 1yr)
white matter of brain -> paralysis and death (goats 2-4 months)
caprine arthritis encephalomyelitis virus tx
- no vac
- cull infected animlas
- remove kids form infected does
caprine arthritis encephalomyelitis virus diagonstics
- elisa
- pcr