Position 22 of the V3 loop is associated with co-receptor usage and disease progression in HIV-1 subtype B isolates

Our goal in this study was to analyze position 22 of the V3 loop associated with co-receptor usage and disease progression in human immunodeficiency virus type 1 (HIV-1) subtype B infection. Bioinformatics approaches were used to compare the amino acid sequence and secondary structure of the V3 loop of the CCR5-tropic virus and CXCR4-tropic virus in HIV-1 subtype B. HIV-1 subtype B V3 amino acid sequence files in the FASTA format were collected from the HIV Sequence Database. The amino acid sequences of different tropism were multiple-aligned with CLUSTAL W program, and the frequencies of the amino acids at each position of the V3 loop sequences of two groups were calculated and sorted in descending order. The secondary structure of the consensus V3 amino acid sequences from CCR5-tropic and CXCR4-tropic viruses were predicted with the APSSP2 method. The amino acids at positions 11, 22, and 25 of V3 were different between the CCR5-tropic virus and CXCR4-tropic virus. The consensus amino acid frequencies were found to be 71.9% S, 66.7% A, and 56.0% D for the CCR5-tropic virus and 50.0% R, 57.1% T, and 26.2% Q for the CXCR4- tropic virus at positions 11, 22, and 25, respectively. There was a strong association between the identity of the residues at position 11, 22, and 25 of the V3 loop amino acid sequence and CD4+ T cell counts of different patients. The change of the residue at position 22 in the R5-tropic or X4-tropic viruses is expected to likely change the secondary structure to be similar to the X4-tropic or R5-tropic viruses. Our study indicates that position 22 of the V3 loop amino acid sequence is significantly associated with viral tropism and disease progression in HIV-1 subtype B.