Retroviridae Overview

Morphology

• Fragile, enveloped RNA viruses with roughly spherical spike proteins
• Genome has 3 genes:
  • gag: group-specific antigen coding gene, encodes capsid proteins
  • pol: encodes reverse transcriptase (RT) and integrase
  • env: encodes envelope spikes, and can be used in diagnosis and subunit vaccines
• Both ends of genome show a promoter (LTR: long terminal repeat)

Antigenicity

• Group-specific antigens (gag's) are shared by all isolates of each virus
  • This can be exploited by diagnostic tests
• Lentiviruses show variation by mutation, making vaccination difficult

Virulence and Pathogenesis

• Replication involves integrating into the host cell genome:
  • Uncoating to release RNA and RT
  • +RNA transcribed to -DNA by RT
  • -DNA becomes circular dsDNA and is integrated into host chromosome by integrase
  • DNA codes for viral proteins using cellular organelles and enzymes
  • Because of this technique, virus replication is much slower, and retroviruses can remain latent
• Tumor production takes 2 forms:
  • Viruses can carry oncogenes within their genome --> tumor production occurs quickly
  • Insertion of the viral LTR switches on proto-oncogenes in the host cell genome --> tumor production can take years

Retrovirus virions are sensitive to heat, lipid solvents, and detergents but are relatively resistant to damage caused by ultraviolet light¹. The Retroviridae are enveloped viruses which contain a single-stranded RNA genome within an icosahedral nucleocapsid. Glycoprotein surface spikes are located on the envelope. Unusually, Retroviruses have a diplod genome: two identical copies of their positive-sense ssRNA are found on the virion¹. During viral replication, reverse transcriptase converts the ssRNA genome to ssDNA. This process is inherently error-prone, and the high rate of mutation gives rise to a wide genetic diversity of virus¹. A dsDNA can then be made from the ssDNA template. This provirus DNA then becomes integrated into the host genome by the actions of the viral enzyme integrase, and remains latent until transcription is initiated by the host cell machinery¹. Proviral DNA then serves as a template for the production of progeny ssRNA genomes and messenger RNA. Once the proviral DNA has been transcribe and translated, the virions assemble and are release by budding through the host cell membrane. This does not always cause lysis¹.

Many Retrovirus genomes contain oncogenes which may be expressed when integrated to the host genomes. However, oncogenes are not a requirement for tumour induction, and some Retroviruses can cause tumours without carrying oncogenes. The Retroviral genome has four coding regions. The "gag" region codes for the matrix protein, nucleoprotein and capsid, and "pro" encodes a protease¹. Reverse transcriptase is coded by the "pol" region, whereas "env" gives rise to the envelope and receptor binding. An additional, specific cellular transporter RNA is required for replication and present within the virion.

References

1. Wise, D J and Carter, G R (2005) A Concise Review of Veterinary Virology, IVIS.