Retroviridae

Retroviridae
 

Virion Structure

• Enveloped Virus
• 2 copies (identical) of mRNA for DS DNA genome. Each is bound by a molecule of tRNA

Characteristics

• Genome replication uses reverse transcriptase (RT) RNA dependent DNA polymerase
• Double stranded DNA copy of the viral genome is stably integrated into the host cell genome. This is called the provirus.

Exogenous Retroviruses

• retroviruses are passed horizontally (virions are produced)

Endogenous Retroviruses

• Endogenous retroviruses are found in the germ-line. Offspring inherit endogenous retroviruses through the germ-line.
• Comprise of about 8% of the human genome.

Genome Organization 

Simple Retroviruses

• Gag, PR, Pol, Env genes only 
• Gag (for group-associated antigen) encodes the GAG polyprotein
• Pol gene encodes the polymerase (POL) polyprotein
• Env encodes the envelope (ENV) polyprotein
• Complex Retroviruses
  • Have slightly larger and more complex genomes.
  • Encode a variety of regulatory and accessory proteins 

Proteins  

• Proteins of the virus core or capsid, gag gene products
• Matrix (MA): Has role in virus assembly.
• Capsid (CA): Major structural protein, role in assembly.
• Nucleocapsid (NC): A basic protein (+charge) that binds the viral genome. Facilitates reverse transcription.  
• (Protease, PR) :cleave viral polyproteins at specific sites 
• Products of the pol gene 
  • Reverse transcriptase (RT): viral genome synthesis 
  • Integrase (IN): insertion of retroviral ds DNA into the host cell genome
  • (Protease, PR) : cleaves precursor polyproteins in the newly budded (but immature) virion
• Products of the env gene
  • Surface glycoprotein (SU): attachment
  • Transmembrane glycoproteins (TM): fusion

Replication Overview 

• Attachment 
• Penetration (fusion) 
• Nucleocapsid is released into cytoplasm 
• Reverse transcription of viral RNA to generate a double stranded DNA copy Viral DNA is integrated into the host cell DNA (viral IN protein). The integrated DNA is called the ‘provirus’ 
• After integration, virus may be latent, or expression of mRNA can occur immediately 
• Synthesis of viral mRNA (by host cell RNA polymerase) 
• Synthesis of viral proteins 
• Capsid assembly (package RNA genome) and budding 
• Maturation (cleavage of gag-pol precursor)  

Integration

• The integration of a retrovirus activates a cellular proto-oncogene. ○ Integration is random (as regards the host genome) and may disrupt cellular genes - in rare instances this can lead to transformation