Walsh & Hoyt: Organization and Genomic Structure

Lentiviridae nucleic acid consists of two homologous single- stranded RNA molecules of about 9.5 kb in length. The RNA genome is diploid and contains both structural and non-structural genes. Three critical structural genes found in all lentiviruses are called gag, pol, and env. Gag produces several proteins, including the matrix and capsid proteins that are involved in virion assembly, and the nucleocapsid protein that coats the viral RNA. Pol codes for the critical enzymes involved in viral replication including reverse transcriptase, protease, and integrase. Of these, reverse transcriptase is the most important. Reverse transcriptase acts in three ways: as an RNA-dependent DNA polymerase, as a DNA-dependent DNA polymerase, and as a ribonuclease. The gene for reverse transcriptase does not have a 3' exonuclease-proofreading activity, resulting in a high error rate during replicationapproximately one error in 104 nucleotidesand this contributes to the marked genetic variability of HIV. Env produces a precursor glycoprotein, gp160, which is cleaved to form two smaller glycoproteins, gp120 and gp41, both of which are required for binding and fusion of the virus to host cells.