Retroviruses - Retroviridae Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics

Retroviruses - Retroviridae Virion Spherical enveloped particle. Diameter 100 nm. Envelope assembled at plasma membrane. Icosahedral or conical capsid. Contains reverse transcriptase.

Retroviruses - Retroviridae Genome Linear ss RNA, positive sense. Two identical molecules, 7–10 Kb, packaged in virions. 5’ cap, 3 poly(A) tail.

Retroviruses - Retroviridae Genes and proteins mRNAs transcribed from integrated provirus DNA by RNA polymerase II. Three major genes, each translated as a polyprotein and cleaved into mature proteins: gag: nucleocapsid proteins pol: reverse transcriptase, protease, and integrase env: envelope proteins Gag and Pol proteins made on unspliced mRNA. Env proteins made on singly spliced mRNA. Lentiviruses and human T-cell leukemia viruses have additional regulatory genes expressed on multiply spliced mRNAs.

Retroviruses - Retroviridae Viruses and hosts Seven genera are recognized: Alpha- to Epsilonretrovirus, Lentivirus, Spumavirus. Simple retroviruses: Rous sarcoma virus (chickens), mouse mammary tumor virus (mice), Jaagsietke sheep retrovirus. Lentiviruses: human, feline, bovine, and simian immunodeficiency viruses Spumaviruses: simian foamy virus.

Retroviruses - Retroviridae Diseases Humans: AIDS, leukemia. A variety of cancers in monkeys, mice, cats, sheep, birds, etc.

Retroviruses - Retroviridae Distinctive characteristics Two identical copies of genome per virion. Genome RNA converted to DNA by reverse transcription. A cellular tRNA used as primer to initiate reverse transcription.

Virion Retroviruses have a unique replication cycle based on reverse transcription and integration of their genomes

Virion Viral proteins derived from the gag, pol, and env genes are incorporated in virions Fig. 25.1 A typical retrovirus virion.

Virion Fig. 25.2 Structure of retrovirus RNA.

Virion Retroviruses enter cells by the fusion pathway Fig. 25.3 Early phase of retrovirus life cycle.

Genome Viral RNA is converted into a double-stranded DNA copy by reverse transcription 1. Synthesis of minus-strand strong-stop DNA. 2. Removal of template RNA. 3. Strand transfer. 4. Copying of full-length genome. 5. Removal of template RNA. 6. Synthesis of plus-strand strong-stop DNA. 7. Removal of tRNA and ppt primer. 8. Second strand transfer. 9. Extension of both DNA strands.

Genome Viral RNA is converted into a double-stranded DNA copy by reverse transcription Fig. 25.4 Reverse transcription.

Genome A copy of proviral DNA is integrated into the cellular genome at a random site Fig. 25.5 Integration of proviral DNA into host cell DNA.

Genes and proteins Sequence elements in the long terminal repeats direct transcription and polyadenylation by host cell enzymes Fig. 25.6 Production of retrovirus RNAs.

Genes and proteins Differential splicing generates multiple mRNAs The Gag/Pol polyprotein is made by suppression of termination and use of alternative reading frames Fig. 25.7 Ribosome frameshifting.

Genes and proteins Virions mature into infectious particles after budding from the plasma membrane Env protein ER -> Golgi -> plasma membrane Glycosylated, and cleaved to SU and TM by host enzyme Gag and Gag/Pol Released into cytosol Assemble viral core, bud through plasma membrane Cleavage of polyproteins by viral protease At this stage virions become infectious Viral protease could be an important target for antiviral chemotherapy

Genes and roteins Acute transforming retroviruses express mutated forms of cellular growth signaling proteins Fig. 25.8 Promoter insertion near proto-oncogenes can lead to cell transformation and tumor formation.

Genes and proteins Retroviruses lacking oncogenes can transform cells by insertion of proviral DNA near a proto-oncogene Fig. 25.9 Promoter insertion near proto-oncogenes can lead to cell transformation and tumor formation.

Genes and proteins Retroviruses lacking oncogenes can transform cells by insertion of proviral DNA near a proto-oncogene

Key Terms Promoter occlusion Chemokine Proto-oncogene Cytosol Proviral DNA Pseudoknot Quasispecies Reverse transcriptase Ribonuclease H Chemokine Cytosol Lumen Myristate Oncogene Polyprotein Preintegration complex