Retroviruses Flashcards
Key features of retroviruses
- two copies of RNA genomre in each viral particle
- reverse transcribe RNA to DNA
- DNA “provirus” integrates into cellular DNA
- establish PERSISTENT infections
A simple retrovirus genome
gag pol env
core structural proteins
enzymes for replication reverse transcriptase, integrase, protease
envelope glycoproteins
Retroviruses infect cells by binding to a receptor
Replication:
Integration is necessary for a productive viral lifecycle
- simple retroviruses (eg FeLV) integrate in dividing cells
- lentiviruses (egHIV) can integrate in non-dividing cells
Persistent infections
- integration of the provirus
- persistence in the genome (no disease in many cases)
- maximises chance of viral transmission to new host
- ALL retroviruses integrate
Retroviral Assembly
-some retroviruses assemble at the pericentriolar region of the nucleus, then fully assembled particle then migrating to the cell surface
FeLV-discovered in Glasgow
- can cause immunosuppression, tumours, anaemia
- 3 subgroups: A, B and C, classified according to the viral envelope glycoprotein (gp70)
- FeLV-A - subgroup isolated from all infected cats
- FeLV- B and C subgroups are generated within the host
- vaccines available
Bovine Leukaemia Virus
-Causes enzootic bovine leukosis
• Virus latently infects B lymphocytes
• No free virus in blood
• Antibodies in persistently infected cattle
• Viral Tax protein trans-activates cellular genes
• Products of trans-activated cell genes may be oncogenic
Bovine Leukaemia Virus
- transmission via milk, blood
- vertical or horizontal transmission
Oncogenic retroviruses
- a Avian leukosis viruses (ALV)
- b Jaagsiekte sheep retrovirus (JSRV)
- Feline leukaemia virus (FeLV)
- Bovine leukaemia virus (BLV)
Mechanisms of retroviral oncogenesis
- oncogene capture and transduction
- insertional activation
- other mechanisms
Rapid oncogenic transformation: in vitro
Infection with oncogenic virus (e.g. Rous sarcoma virus)
- loss of contact inhibition
- increased growth rate
Human Immunodeficiency Virus
origin chimpanzee?
Endogenous retroviruses (ERVs)
- genomes persist in host DNA
- transposable (mobile)
Retroviruses as clinical tools
-gene therapy
Integration of DNA provirus
- may lead to cancer
- exploited for gene therapy