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