Retrovirus

• Retroviruses


  A group of RNA viruses that inserts a DNA copy of its genome into the host cell in order to replicate
• Retroviruses are implicated in a series of human and animal tumours such as leukaemias, mammary tumours or skin cancer
• Reverse transcriptase


  An enzyme required for reverse transcription of viral RNA to produce viral DNA strands
• Retrovirus genome contains three genes

  • Group specific antigen gene (gag)
  • Polymerase gene (pol)
  • Envelope gene (env)
• Polymerase gene


  Encodes the three enzymes which catalyzes the steps of the retroviral infection: Protease, Reverse transcriptase, Integrase
• Mechanism of retrovirus replication

  1. Entering cells through direct fusion or attachment to receptors

  2. Using reverse transcriptase to create complementary DNA (cDNA) from their RNA

  3. Integrating viral DNA into the host genome, forming a provirus

  4. Transcribing and translating viral genes

  5. Gathering virus particles and coming out of host cell
• Retrovirus replication


  1. Reverse Transcription: Synthesis of DNA from an RNA template using reverse transcriptase

  2. Transcription: Viral genetic information presented to host cells for viral protein production

  3. Translation: RNA used to produce viral proteins
• HTLV


  A form of slow-transforming RNA virus implicated in human cancer
• Four types of HTLV are recognized (HTLV 1 -4)
• HTLV 1 infection


  Link to Adult T cell Leukaemia Lymphoma (ATLL)
• HTLV 2 infection


  Implicated in causation of T-cell variant of hairy cell leukaemia
• HTLV 1 is endemic in parts of Japan and West Indies where the incidence of ATLL is high
• HTLV-2 is prevalent among the indigenous populations in Africa and the Indian-American tribes in Central and South America as well as among drug users in Europe and North America
• HTLV 1 is transmitted through sexual contact, by blood or to infants during breastfeeding
• HTLV-II is transmitted through parenteral routes, particularly injection drug use
• A common mechanism by which retroviruses cause cancer is the activation of oncogenes
• HTLV 1 over activates T-cells, key immune cells in the body, causing them to become cancerous
• ATLL develops in around 5 percent of people infected with HTLV 1
• ATLL can progress slowly or aggressively
• The HTLV-1 virus inserts itself into one type of T-cell, and, to begin with, remains there in a 'latent' state, not releasing any new virus particles or causing any ill effects
• In around five per cent of HTLV-1 carriers, after decades of latency the virus reawakens and affects the T-cells' functioning
• ATLL has a high relapse rate after treatment with chemotherapy and antiviral drugs
• In people who progressed to ATL, HTLV-1 made infected T-cells highly activated and over-reactive, causing them to over-produce proteins that keep them proliferating and helping them avoid other parts of the immune system that would usually remove rogue cells
• The changes made the overactive T-cells more vulnerable to DNA damage, such as through chemical agents or radiation, accelerating their transition to a cancerous state