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

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

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