Family: Retroviridae Flashcards
Who discovered the first retrovirus?
Francis Peyton Rous
- cancer-causing chicken virus
How does Retroviridae get its name?
retro = reverse, backward —> reverse transcriptase (RNA-dependent DNA polymerase) found in the virion of all members
What is the structure of Retrovirus virions? What is its capsid like? What is it surrounded by?
- enveloped with a three-layer structure
- innermost = genome with a nucleoprotein complex and complex helical symmetry
- icosahedral
- glycoprotein envelop
What is the genome of Retroviruses like?
diploid/dimer of linear positive-sense ssRNA with a 3’ Poly-A tail and 5’ cap
How does the RNA-dependent DNA polymerase of Retroviruses do?
reverse transcriptase uses positive-sense RNA to create dsDNA that is inserted as a provirus into the host genome
What are 4 unique criteria of Retrovirus genomes?
- only diploid gemone
- only positive-sense ssRNA genome that does not serve as mRNA soon after infection
- only genome to encode a reverse transcriptase
- only viral RNA that is synthesized and processed by host cell mRNA processing machinery
What are the functions of the 4 proteins produced by Retrovirus’ genome?
- gag - group-specific antigen that encodes internal structural proteins
- pro - protease
- pol - polymerase; resverse transcriptase and integrase
- env - envelope; surface (SU) and transmembrane (TM) envelope glycoproteins
What genus does FIV and FeLV belong to?
FIV = Lentivirus (immunodeficiency!)
FeLV = Gammaretrovirus
What are 6 important biological properties of Retroviruses?
- ability to acquire and alter host-derived genetic sequences
- ability to integrate into host cell genome
- activation/inactivation of specific genes near the integration sites
- ability to undergo mutation and recombination
- ability to be used as vectors to deliver genes
- induction of immunosuppression or immune-mediated disease
In what 3 ways can Retroviruses induce oncogenesis?
- INTEGRATION of the provirus upstream of an oncogene causing the viral long terminal repeat to upregulate the oncogene (slow onset of tumor)
- DEFECTIVE RETROVIRUSES cannot replicate, but have picked up an oncogene from the host cell and propagates by co-infecting with a replication-competent virus (highly oncogenic and quick)
- RETROVIRAL GENOME INTEGRATION of a viral gene that can interfere with cellular genes that control host cell transcription
Retrovirus mechanism of viral DNA induced into host DNA:
How are endogenous retroviruses (ERV) able to be passed vertically? What are the 3 classes of ERVs?
integration of proviruses into the chromosomes of germ cells passed down via sperm of egg DNA
CLASS I - gamma-related
CLASS II - beta-related
CLASS III - spuma
How are endogenous retroviruses regulated?
regulated by genes that are usually silent, but are activated by irradiation, mutagens, or carcinogens, which results in the formation of new virions
What are the major receptors for some Retroviruses? How does this cause immunosuppression?
- CD4, CCR5, CXCR4: HIV, SIV
- CD134, CXCR4: TNF-R family, FIV
- CAT-1: MLVe
- Pit-1: FeLV-B, GALV
these receptors are found on immune cells and binding to these receptors allows for infection
What are the 6 steps to Retrovirus replication?
- interaction between viral envelop protein (Env) and cellular receptors
- membrane fusion and entry of viral capsid
- viral genomic RNA is reverse-transcribed into cDNA using viral reverse transcriptase and a packaged cellular tRNA as the primer
- viral cDNA enters the nucleus in the form of a pre-integration complex and is inserted into the host genome
- DNA provirus is transcribed by host machinery to produce gRNAs that are packaged into mRNAs that are translated to generate viral proteins
- viral gag and gag-pol drive vrial assembly at the plasma membrane, where gRNA and some host factors (tRNA) are recruited to allow for the budded virion to mature and become infectious
How does the structure of Retroviruses compare when latent and active?
What syndromes are produced by the 3 major Avian Retroviruses affecting chicken?
- avian leukosis viruses - lymphoid leukosis, osteoperosis, renal tumors
- avian erythroblastosis, myeloblastosis, and myelocytomatosis viruses - erythro/myeloblastosis myelocytomatosis, hemangioma, sarcomas
- rapidly transforming (Rous Sarcoma) virus - sarcoma
Retrovirus-induced oncogenesis:
What is avian leukosis/sarcoma complex virus (ALV)? What are the 6 most common diseases?
alpharetrovirus that belongs to subgroups A, B, C, D, E, and J
- lymphoid leukosis
- erythroblastosis
- myxosarcomas
- myeloblastosis
- osteopetrosis
- fibrosarcomas
What is the natural host for all viruses of the leukosis/sarcoma group? In what 2 ways is it transmitted?
chickens
- VERTICAL: eggs
- HORIZONTAL: chicken to chicken from feces
What syndromes are caused by avian leukosis virus, respiratory syncytial virus, and avian myeloblastosis virus? What viral oncogenes cause each?
ALV = erythroblastosis - c-erbB
RSV = sarcoma - v-src
AMV = myeloblastosis - v-myb
What are the 4 common clinical signs of avian leukosis/sarcoma complex virus (ALV)? What 3 postmortem lesions are expected?
- depression
- emaciation
- weight loss
- low mortality
- focal grey to white tumors in the bursa, liver, spleen, kidney, and heart
- large liver
- lymphoplastic cells
What are 4 differential diagnoses for avian leukosis/sarcoma complex virus (ALV) infection?
- egg drop syndrome virus
- Marek’s disease virus
- fowl poxvirus
- chicken anemia virus
What is bovine leukemia virus (BLV)? How does it typically affect herds? How is it spread?
deltaretrovirus causing disease in adult cattle with lymphocyte and lymph node neoplasia
prevalence is high, but only few develop fatal lymphosarcoma
contact with contaminated blood from an infected animal from tagging, dehorning, tattooing, multiple use needles, and rectal palpatation
When do most bovine leukemia virus (BLV) infections occur?
early in life when virus is transmitted in the milk
There is typically no clinical signs of bovine leukemia virus (BLV) infection early in life. What are the 7 common signs of infection of adults?
- congestive heart failure
- decreased milk production
- paralysis due to neuronal involvement
- progressive weight loss
- recurring bloat
- weakness
- enlargement of all lymph nodes with palpable lumps on the neck, shoulder, and udder***
What happens in animals that develop disease following bovine leukemia virus (BLV) infection?
lymphoid tumors in lymph nodes, heart, spleen, kidneys, uterus, spinal meninges, and brain
What causes oncogenesis in bovine leukemia virus (BLV) infection? What are the target cells?
integration of bovine proviral v-onc genes into cellular DNA
B lymphocytes
How is bovine leukemia virus (BLV) diagnosed? What helps destroy BLV infectivity?
detection of BLV antibodies in the blood or milk
pasteurizing or freezing colostrum/milk
What is another name for Visna Maedi? What is it? What is its etiology?
(Maedi = dyspnea, Visna = wasting)
ovine progressive pneumonia
incurable, slow-acting, wasting disease of sheep
Retrovirus
What 2 things is Visna Maedi associated with?
- thin ewe syndrome
- hard bag (lungers) = firm enlarges udder with no milk resulting from an accumulation of fibrous tissue
How does the Retrovirus causing Visna Maedi enter cells? How does infection spread?
Trojan Horse mechanism into monocytes
nanoparticles are internalized within cells and then release high levels of toxic ions
What does Jaagsiekte sheep retrovirus (JSRV) cause?
(jaagt = driving, ziekte = sickness)
contagious ovine pulmonary adenocarcinoma (OPA)
How do the tumors from Jaagsiekte sheep retrovirus (JSRV) infection arise? How can they be identified molecularly?
from epithelial cells in the lower airway
contain markers of type II pneumocytes and alveolar or bronchiolar epithelial cells
What is another name for caprine retrovirus? What does it cause?
big knee virus
caprine arthritis-encephalomyelitis
What are the 5 main clinical signs associated with caprine arthritis-encephalomyelitis?
- arthritis
- mastitis
- encephalitis
- interstitial pneumonia
- progressive weight loss
(caprine retrovirus - big knee virus)
How is caprine retrovirus primarily transmitted? What are the 2 most characteristic lesion?
to kids through colostrum/milk from infected does
- polyarthritis in adult goats
- encephalomyelitis in kids
What does enzootic nasal tumor virus (ENTV) cause? What causes death in this instance?
enzootic nasal adenocarcinoma (ENA) arising from ethmoid mucosa, which has the ability to invade the sinuses and adjacent bony structures
anorexia and weight loss
What is a common viral etiology of mouse mammary tumors?
mouse mammary tumor virus (MMTV), a Retrovirus
What are 5 other names for equine infectious anemia? What is its etiology?
- swamp fever
- mountain fever
- slow fever
- equine malarial fever
- Coggins disease
equine infectious anemia virus (EIAV), a Lentivirus (Retroviridae)
How does equine infectious anemia virus (EIAV) affect its host? How is it spread? What is unable to transmit the virus?
infects horses for life, producing intermittent attacks of illness followed by periods of recovery
mechanically through insect vectors (horse, stable, deer flies), infected syringes, needles, or surgical equipment (only takes one drop blood)
mosquitoes
How does equine infectious anemia virus (EIAV) affect fetuses? Can symptomatic stallions infect mares?
can cross the placental barrier and cause fetal infection
YES
How is equine infectious anemia virus (EIAV) infection able to persist?
EIAV incorporates its genomic code into macrophage DNA, allowing it to reproduce within and kill the macrophage
(+ can do dormant in host)
What are the 3 clinical forms/stages of equine infectious anemia?
- ACUTE/SUBACUTE: 7-30 days; diphasic fever, off feed, severe anemia, weight loss, stumbling/unsteady gait, edema, and sudden death; may come up negative on a test
- CHRONIC: positive test; weight loss, weakness, anemia, swelling of lower leg, chest, and abomen (ventrum), and reoccurance after symptoms subside
- INAPPARENT: healthy animal - no fever or anemia (95%)
What is the gold standard for diagnosing equine infectious anemia? What else can be done?
Coggin’s test (blood)
- ELISA rapid test (false positives)
- Western blot (viral proteins)
- qPCR (proviral DNA)
What happens once an equid is infected with equine infectious anemia virus (EIAV)? What is the key to prevention?
carriers for life
- no vaccines
identification and control of infected horses
- eradication
What causes feline immunodeficiency? What is it very similar to?
feline immunodeficiency virus (FIV), a Lentivirus (Retroviridae)
the virus that causes AIDS (HIV) in humans
- can be used as a model for AIDS research
When is feline immunodeficiency virus (FIV) most commonly found in a cat? How is it shed? What is it unable to be transmitted to?
after cat fights
shed in the saliva of infected cats (bite wounds!)
humans and dogs
What are 5 common signs of feline immunodeficiency virus (FIV) infection? What other virus has similar symproms in cats?
(non-specific)
1. lethargy
2. loss of appetite
3. fever
4. lymphadenopathy
5. weight loss
FeLV
What cells does feline immunodeficiency virus (FIV)? What does this cause?
- T cells
- B cells
- macrophages
- CNS cells
decreased CD4+ T cell response, leading to immune dysfunction
What is a characteristic oral lesion of cats infected with feline immunodeficiency virus (FIV)? What is commonly found on histopathology?
severe lymphoblastic stomatitis with marked hyperemia and ulcerations in the palatoglossal folds
lymphopenia (decreased B and T cells due to immune tropism)
What is feline leukemia virus (FeLV)? How is feline sarcoma virus (FSV) related?
gammaretrovirus associated with neoplastic disease and immunosuppression
defective virus derived from FeLV that contains an oncogene (v-fms) in the place of he env gene
When is feline leukemia virus able to survive in the environment? In what 4 ways is it transmitted?
wet conditions
- VERTICAL: cat to kitten either in utero or during nursing
- HORIZONTAL: infected saliva, tears, and urine ingestion or mutual grooming
- fecal-oral is rare
- bite wounds
What is the tropism of feline leukemia virus (FeLV)? What tumor is most commonly associated?
T-lymphocytes
lymphosarcoma - alimentary, multicentric, leukemic, thymic
What are the clinical signs of feline leukemia virus (FeLV) infection?
- loss of appetite, anorexia, weight loss
- anemia
- persistent diarhea
- poor coat condition
- conjunctivitis, keratitis, URT infection
- behavior changes
- neurological disorders
- abortion
What gives rise to the leukemogenic FeLV-B? How does this strain differ? What causes the leukemia?
exogenous FeLV-A recombines with endogenous FeLV sequences
uses different receptors for attachment, so it has a broader tropism
insertional mutagenesis
How does CBC help diagnose feline leukemia virus (FeLV) infection?
ANEMIA
- lymphopenia
- neutropenia
- thrombocytopenia
- immune-mediated hemolytic anemia
What is the prognosis of feline leukemia virus (FeLV) infection? What should owners look out for?
poor, but cats can survive for prolonged periods of time (median = 2.5 years)
weight loss, appetite, activity level, elimination habits, mouth/eye appearance, behavior
What species does simian immunodeficiency virus (SIV) target? What are the 2 best models?
chimpanzees (Pantroglodytes) - the origin of HIV-1 pandemic in humans
- African gree monkeys
- sooty manhabeys
(reports of illness is anecdotal and conflicting - some animals suffer with severe illness and others live for decades)
What genus of retrovirus affects fish? What 2 are the most common?
epsilonretrovirus —> neoplasia in fish
- walleye dermal sarcoma virus
- snakehead retrovirus
