Microbiology 5 - Retroviruses Retroviruses - Family - Retriviridae o Seven general genus in this family o Five of these are onco ? - Family of positive sense ssRNA - Enveloped - Replication goes through DNA intermediate o Use reverse transcriptase - Associated with different cancer, HIV/AIDS, and cause degenerative and neurological syndromes History: - 1900's - Wilhelm Ellerman & Olaf Bang o First association of viruses with cancer o Leukemia could be transmitted between chickens - 1911 - Peyton Rous o Similar type of filtrate could transmit solid tumours between chickens and cause identical cancer in chickens o Used a filtrate so no other bacteria could get through - The virus was called avian leucosis virus o Designated retroviruses - 1970's - Baltimore & MartinTemin o Discovered reverse transcriptase o Shattered the thought that the flow of genetic information was from DNA to RNA . This shows RNA to DNA Baltimore Classification - Based on mechanism of mRNA production - Retroviruses are all in group fi; o Single stranded o Use reverse transcriptase Structure: - Retrovirus virions; 80-120nm diameter - Spherical - Phospholipid envelope with knobs protruding SU (surface) TM (transmembrane). Lipid bilayer PR (protease) IN (integrase) MA (matrix) (+) strand mRNA NC (nucleocapsid) RT (reverse transcriptase) CA (capsid) VI SSRNA-RT DNA/RNA dsDNA o The knobs are the ones that recognise certain receptors
- Under the envelope you have the matrix - Then the capsid o Which contains the genome; single stranded RNA (2 copies) o Protected by nuclear capsid proteins - Retroviruses carry the reverse transcriptase enzymes o And other enzymes Genome: - RNA genome is a diploid - 2 copies, ssRNA, capped and polyadenylated - Both RNAs are joined near their 5' ends by hydrogen bonds Looks like mRNA because its capped one end (5' end) o But does not serve as a mRNA immediately after infection - Encode at least 4 genes called 'gag' 'pro' 'pol' and 'env' gag pol env viral RNA genome ALV 5' AAAAAA .... 3' core proteins reverse transcriptase envelope protein Figure 3-4a The Biology of Cancer (® Garland Science 2007) - Pro: o encodes a protease PR o Cleaves the Gag polypeptide into matric, capsid and nuclear capsid - Gag: o (group-specific antigen) protein Will be processed into MA, CA, NC (directly bound to RNA) o Around 2000 copies - Pol: o Encodes enzymes o Reverse Transcriptase " Multi-functional enzyme · DNA polymerase activity · RNA dependent · DNA dependent o RNase H . When there is RNA-DNA hybrid strand it will digest RNA strand away o Integrase " Inserted into host genome If inserted into oncogenes, will convert normal cell into cancer cell - Env o Encodes surface glycoproteins o Encodes transmembrane protein " Sits in the lipid bilayer
Replication Cycle 1. Attachment 2. Penetration 3. Synthesis 4. Assembly 5. Release a. Reverse transcription b. Integration into host cell genome (provirus) c. Viral genome replication (transcription) and viral protein synthesis Attachment - Virus attaches to host cell using surface proteins