Differences in the Length of Gag Proteins among Different HIV Type 1 Subtypes

Abstract

The effect of HIV-1 subtype on Gag protein length was examined in 122 individuals infected with different HIV-1 clades. Except for the P1 protein, a wide variation in the Gag proteins length was noticed. P2 was significantly shorter in 68 non-B with respect to 54 subtype B viruses. Nearly 85% of subtype B gag sequences harbored P2 with 14 or more amino acid (aa) residues, while 75% of non-B subtypes had P2 with 13 or less aa (p < 0.0001). The P7 protein was one residue shorter in 64.2% of non-B specimens but only in 9.3% of subtype B isolates (p = 0.0001). Overall, the P6gag protein length was modified by the presence of insertions, deletions, and stop codons in 89 (73%) of the tested population, but was mainly dependent of changes in non- B compared to B viruses (97% vs. 42.6%, p < 0.0001). However, insertions at P6(gag) (from 1 to 9 aa) were significantly more frequent in B than in non-B viruses (33.3% vs. 4.4%; p = 0.00002). Overall, conserved Gag residues and aa motifs, regardless of the genetic subtype, were 68.7% in P1, 54% in P7, 33.3% in P2, and 25% in P6(gag) proteins. In summary, length variation in Gag proteins is extensive across different HIV-1 subtypes, and could influence protein structure and function. The effect of Gag variation on the viral cycle among different HIV-1 clades needs to be further investigated.