Molecular Biology of Retroviruses
- Virions contain single-stranded, linear, positive-sense RNA that is contained within the viral capsid, or outermost protein coat
- In retroviruses, an icosahedral capsid encloses a helical nucleocapsid
- Genomes typically contain 7000-10,000 bases of RNA
- Genomic RNA is capped and polyadenylated
- Virions are engulfed by a lipid-containing envelope with glycoprotein surface projections
- Virus particles appear spherical in electron microscopy as virions are enveloped
- Reverse transcriptase is carried in the virion and has three distinct enzymatic functions
- DNA-dependent-DNA polymerase(meaning it can make DNA from DNA)
- RNA-dependent DNA polymerase (meaning it can make DNA from RNA)
- RNase (degrades RNA/DNA hybrids formed during replication)
- Replication takes place in the nucleus of the host cell
- Viral replication requires the presence of a tRNA primer
- Retrovirus replication requires a mandatory integration step, carried out by the viral enzyme integrase
- Retroviruses, being RNA, must be transcribed into their DNA form (called the provirus) via the enzymatic activity of reverse transcriptase before being integrated into the host genome (also DNA)
- Proviruses exist as covalently closed circles, although viral integration is thought to involve a linear intermediate
- Mandatory integration occurs at random sites in the host genome
- Virus consists of three main genes
- Glycoprotein antigen (gag): responsible for producing proteins essential to retrovirus structure (matrix protein, capsid protein, nucleocapsid protein)
- Polymerase (pol): responsible for producing enzymes essential to retrovirus survival (rreverse transcriptase, integrase, protease)
- Envelope (env): responsible for producing envelope glycoproteins that serve as receptors that engage in cellular binding (surface envelope proteins and transmembrane envelope proteins)
- Each of these genes gives rise to polyproteins that are later cleaved by viral protease into smaller proteins
