Retroviruses.docx

Retroviruses are family of enveloped positive sense ssRNA viruses that replicate through DNA intermediate using reverse transcriptase. Can cause AIDS, cancers, leukaemia etc. Retrovirus structure Spherical shape. 80-120nm Enveloped outer layer= phospholipid membrane acquired from the host cell Has t...

Retroviruses are family of enveloped positive sense ssRNA viruses that replicate through DNA intermediate using reverse transcriptase. Can cause AIDS, cancers, leukaemia etc. Retrovirus structure Spherical shape. 80-120nm Enveloped outer layer= phospholipid membrane acquired from the host cell Has transmembrane and surface proteins attached to the phospholipid membrane. Matrix Capsid Enzymes such as proteases, integrase, and reverse transcriptase. Retrovirus genome RNA genome is diploid. SsRNA Resembles mRNA. Capped and polyadenylated. Encode at least 3 genes (structural proteins) called gag, pol and env. Pol gene encodes for protease, reverse transcriptase, and integrase. Gag gene encodes for the matrix, capsid and the nucleocapsid. Env gene codes for surface glycoproteins and transmembrane proteins. Retrovirus replication cycle Attachment Penetration Synthesis Assembly Release Once entered in the cell via endocytosis or fusion of envelope with the plasma membrane. It sheds the outer layers of, so the nucleic acid becomes exposed in the cell cytosol. ssRNA is converted into dsDNA using reverse transcriptase. This forms a RNA and DNA intermediate. The ssDNA then replicates into double stranded DNA. The dsDNA integrates into host chromosome using enzyme integrase. (integration is irreversible). Some retroviruses progress onwards and some stay in the genome and be latent= provirus. Each time the host cells genome divides, it produces a copy of integrated viral genome. Transcription and translation happen using host cell metabolic machinery making mRNA. These strands are used to synthesise viral proteins. Assembly happens and the virus is released from the cell via budding. HIV is a lentivirus that causes AIDS. Can be caused due to sexual transmit and bodily fluids. HIV does not survive outside of the body and cannot reproduce outside of the host cell. Life cycle of HIV Virus gp120 (glycoprotein) binds to surface molecules CD4 of T helper cells, macrophages etc. Co-receptors are required for the infection. CXCR4 CCR5 Fusion Viral envelope fuses with cell membrane (gp41) releasing contents into the cell. Replication RNA converted into DNA by reverse transcriptase. Integrase inserts the viral DNA into host cells chromosome. It may remain latent for years and called a provirus. The viral genome is transcribed and translated to produce the viral proteins. Assembly New viruses are made. Release New viruses bud through the cell membrane. The presence of accessory genes allows for more effective and vigorous replication of the retrovirus. Can be fatal to the host cell. The phases of the infection. The first phase of the infection is the acute phase. There is a sharp peak for about 10-12 weeks. Symptoms include flu-like symptoms such as fever. The amount of T cells rapidly drops. After 10-12 weeks, it enters clinical latency period. No symptoms are felt. T cell count decreases slowly whilst the HIV slowly increases. After 6-7 years, T cell count drops the threshold. The immune system becomes weakened, and the last stage called AIDS is entered where the HIV copies grows to a fatal number. AIDS associated diseases. Gastrointestinal Symptoms Abdominal pain Diarrhoea Weight loss Infection of GI tract. Respiratory Symptoms TB Lung cancer Neurological Symptoms Headaches Memory loss Skin disorders Symptoms Herpes Thrush Eye infections NO CURE FOR HIV There are several classes of drugs used in combination to treat HIV infection and needs to be taken all life. Treatments Anti- retroviral therapy Nucleotide or nucleoside RT inhibitors Integrase inhibitors. You do not need to know all HIV accessory genes, but need to know at least some of the functions they perform. As your summer exam is going to be in essay format, this would be a good example of some extra reading - providing more information on accessory genes, that is of course if the question is on HIV.