Retroviral Replication
Retrovirus replication follows the generalized steps of the replication of enveloped viruses with some uncommon features.
The Virion
Ø Located at the virion surface are glycosylated envelope (Env) proteins. The structural proteins of the matrix and nucleocapsid core are nonglycosylated and are referred to as Gag proteins. Polymerase (Pol) proteins are associated with the nucleocapsid and RNA and are responsible for reverse transcription and integration.
Ø The viral capsid contains two copies of the RNA genome, each of which has a cellular tRNA molecule bound to it. The virion also contains about 50 copies of reverse transcriptase.
Ø Under the electron microscope, different retroviruses often look different because of the shapes of their capsids.
Viral Genome
Ø All retroviruses have a somewhat similar genome: “gag--pol--env”, which is expressed to produce approximately 8 virion proteins.
Attachment
to Host Cell
Ø Retroviruses use their surface glycoproteins to attach to specific plasma membrane receptors, allowing for the fusion of viral and cellular membranes.
Ø This attachment is highly specific in terms of the species and/or cells that will be affected.
Penetration
of the Cell
Ø The interaction of viral surface glycoproteins to receptor molecules triggers a conformational change in the viral glycoprotein, which then mediates the fusion of the lipid bilayers of the viral and cell membranes allowing the virus to introduce its genetic material into the host cell.
Envelope Glycoprotein
Complex
Ø Retroviruses have an envelope glycoprotein complex which includes two polypeptides:
• SU-an external,glycosylated hydrophilic peptide
• TM-membrane-spanning protein
Ø Both polypeptides are encoded by the env gene.
Cell membrane
binding
Ø SU binds to a specific receptor molecule on the cell. This activates the membrane fusion-inducing potential of the TM protein and then the viral and cellular membranes fuse.
Reverse Transcription
Ø See Part 2-Reverse Transcription of our TIP
Retrovirus Assembly
Assembly
Ø Research has shown that even though the shapes of different capsid shells vary, retroviruses may assemble using one common mechanism.
Ø The assemblage of components will occur under the plasma membrane.
Ø This immature virus-like particle (VLP) will bud off. Inside this virion are long Gag proteins
Ø The final step is the cleavage of Gag and Pol by viral protease.
Assembled and assembling immature VLP
References
Ø
Coffin, JM, SH Hughes, HE Varmus, Retroviruses at the
Ø http://www.accessexcellence.org/RC/VL/GG/retrovirus.html.
Ø http://www.mun.ca/biochem/courses/3107/Topics/retrovirus_replication.html
Ø http://www.mbg.cornell.edu/MBG_Faculty_Detail.cfm?id=30
Ø http://www.scripps.edu/newsandviews/e_20030811/onpress.html
Ø http://w3.ouhsc.edu/mi/faculty/Sakalian.html