Figure 5-1.4.4(b): Replication cycle of retroviruses.

(Adapted from Hu W-S, Pathak VK. 2000. Design of Retroviral Vectors and Helper Cells for Gene Therapy. Pharmacol Rev, 52: 493–511)

Retroviral genome

The integrated provirus comprises three genes (gag, pol and env). The gag gene encodes a viral structural protein, pol encodes the reverse transcriptase and integrase and env gene encodes viral envelope proteins. Retrovirus can be classified as oncoviruses, lentiviruses, and spuma-viruses. Oncoviruses are simple whereas lentiviruses and spuma-viruses are complex retroviruses.

Viral genomic RNA is synthesized by transcription from a single promoter located in the left LTR and ends at a poly-A site in the right LTR. Thus, the full-length genomic RNA is shorter than the integrated DNA copy and lacks the duplicated LTR structure. The genomic RNA is capped and polyadenylated, allowing the gag gene to be translated. The pol gene is also translated by read through, producing a Gag–Pol fusion protein, which is further processed into several distinct polypeptides. Some of the full-length RNA also undergoes splicing, eliminating the gag and pol genes and allowing the downstream env gene to be translated. Two copies of the full-length RNA genome are incorporated into each capsid requiring a specific cis -acting packaging site termed ψ. The reverse transcriptase/ integrase are also packaged.