V3 sequences in primary HIV-1 infection

Objective : To determine HIV-1 genomic RNA and proviral DNA sequences of the third hypervariable region (V3 loop) of the envelope protein in patients with primary HIV-1 infection (PHI), and to compare these sequences with sequences from patients with more advanced HIV-1 infection. Methods : Sera and peripheral blood mononuclear cells were collected from 24 patients with PHI living in Geneva. V3 sequences were determined using direct solid-phase sequencing on polymerase chain reaction (PCR) products. Results : A 100% homology rate was observed between HIV-1 genomic RNA and proviral DNA paired nucleotide sequences from the V3 region in the 24 patients. Using a limiting dilution approach for three patients, a unique V3 sequence was observed for the genomic RNA. Three out of 24 amino-acid sequences presented the characteristic signature sequence QRGPGR, first described for the HIV-1 LAI isolate, which is associated with lymphocytotropism. These three isolates also presented, for the V3 loop, a characteristic elevated charge (8) at physiological pH in comparison with the other isolates (3-5). There was no significant difference in the distribution of amino acids between the 24 V3 loop sequences from patients with PHI and 245 V3 loop sequences of the B subtype determined in patients with more advanced HIV-1 infection. Conclusion : The paired sequences recovered from HIV-1 genomic RNA and proviral DNA are identical for each of the 24 patients with PHI. Three isolates had the V3 loop characteristic signature sequence QRGPGR first described for the HIV-1 LAI isolate. There is no characteristic V3 loop pattern associated with PHI isolates.