You B, Barre-Sinoussi F, Georges AJ, Mathiot C, Sonigo P; International Conference on AIDS.
Int Conf AIDS. 1992 Jul 19-24; 8: A31 (abstract no. PoA 2169).
Pasteur Inst. Bangui, Central African Republic.
OBJECTIVES: In a vaccine design, based on the envelope glycoprotein, including V3 region, epitopic variability must be investigated. We present here V3 sequences from HIV-1 Central African strains. METHODS: Six HIV-1 variants were isolated from patients at different stages of the disease. Propagation on MT4 cells was performed and proviral DNA amplified in both V3 region and gag gene (position 1180-1420 in Mn isolate). PCR products were then directly sequenced. Sequences are analysed and compared with other published sequences. RESULTS: The V3 region shows conserved structures: terminal cysteine residues, sequence length (35 amino acids), GxG central motif, and proteolytic cleavage sites. However, distribution of the 6 Central African sequences on the dendrogram shows significant heterogeneity with other african sequences including Central African variants as well as other published sequences. Moreover, no peptidic consensus sequence can be deduced: substitutions are dispatched on both sides of the V3 loop top. Four different central tetrapeptidic motifs (GPGR,GPGQ,GSGR,GSGQ), and variable number (from 0 to 2) of possible N-linked glycosylation sites are observed among the 6 Central African strains. The comparison of the V3 variability with those of a conserved region in gag gene, shows the high level of non synonymous substitution rate in the V3 region. This result suggest that a positive selective pressure occurs on the V3 region. This is in agreement with results obtained by other laboratories. CONCLUSIONS: Our Central African sequences show an especially high variability compared with available published sequences. In a vaccine design based on the immunizing properties of the envelope glycoprotein, including V3 region, this observation is disturbing. However, these results must be compared with cross-neutralization assays, to define correlation between primary sequences and serotypes of neutralization.
Publication Types:
Keywords:
- Base Sequence
- Consensus Sequence
- Genes, gag
- HIV-1
- Humans
- Polymerase Chain Reaction
- genetics
Other ID:
UI: 102198178
From Meeting Abstracts