In vivo and in vitro sequence diversity of the V3 env region of HIV type 1 from the Ivory Coast.

Abstract

Nine divergent clades of HIV-1 have been detected in Africa, indicating a far greater genetic diversity of the virus on the continent relative to elsewhere in the world. The envelope of HIV-1, especially the V3 loop, which is implicated in viral tropism and in the neutralizing domain, is considered to be a major target for vaccine research. The authors analyzed proviral DNA and RNA viral sequences of the V3 region of the env gene obtained from the plasma and lymphocytes of six people with AIDS originating from the Ivory Coast. The four men and two women exhibited clinical AIDS and pulmonary tuberculosis. The inferred amino acid sequence of the V3 region derived from the DNA sequences obtained in the study were aligned together with the reference sequence of subtype A from the Los Alamos HIV sequence database. The identity of the conserved tetrapeptide motif at the tip of the V3 loop in all the isolates is GPGQ and is consistent with the common motif sequence found in the database for the A subtype. The major changes in the amino acids are localized in the flanking sequences of the V3 loop. The V3 loop of HIV isolates from patient CI-39 presents a change of D to R in position 25, associated with an unusual change in position 24 of G to D. These mutations were found in both viral RNA sequences and in the proviral DNA sequences from uncultured peripheral mononuclear cells (PBMCs), possibly reflecting an infectious viral variant which is actively expressed in vivo and present in plasma. The change of an acidic amino acid to a basic amino acid at position 25 appears to be an important viral tropism determinant.