Envelope-specific antibody response in HIV-2 infection: C2V3C3-specific IgG response is associated with disease progression

Abstract

HIV-2 promotes an early, strong and broad gp36 and C2V3C3-specific IgG and IgA response. Increase in the IgG response against the envelope C2V3C3 region is associated with increased loss of CD4 T cells in chronically infected patients. These results provide further support for the immune protective role of the C2V3C3 envelope region during HIV-2 infection and have direct implications for HIV-2 diagnosis, clinical management and pathogenesis.

HIV-2 A-subtype gp125C2-V3-C3 mutations and their association with CCR5 and CXCR4 tropism

“…Some of these mutations, like the associated positions 319, 320, 323 and 338, have been observed previously [40,50]. Specifically, recombinant polypeptides representing the gp125 (rpC2-C3) in infected patients, Marcelino and colleagues did not detect reactive IgG antibodies [50]. Similar results were observed with X4-tropic viruses that were resistant to neutralization in a vaccinia virus vector-prime/rpC2-C3-polypeptideboost vaccination strategy [40].…”

“…Similar results were observed with X4-tropic viruses that were resistant to neutralization in a vaccinia virus vector-prime/rpC2-C3-polypeptideboost vaccination strategy [40]. In the first study, the authors examined nonspecific and Env-specific IgA and IgG responses in acute and chronic HIV-2 infection [50], while in the other work, the same team used a mouse model to investigate the immunogenicity and neutralizing response elicited when a recombinant HIV-2 envelope proteins was administered [40].…”

“…Fourteen X4-tropic virus mutations (T309S V3 , V311I V3 , L319R V3 , I320R V3 , S323G V3 , 324-325insR V3 , P325F V3 , 325-326insHS V3 , R32 9K V3 , K338E C3 , Q346R C3 , V353M C3 , T361V C3 and K371E C3 ) formed a very strong and highly significant subcluster (bootstrap value = 0.99). Some of these mutations, like the associated positions 319, 320, 323 and 338, have been observed previously [40,50]. Specifically, recombinant polypeptides representing the gp125 (rpC2-C3) in infected patients, Marcelino and colleagues did not detect reactive IgG antibodies [50].…”

“…These two positions were not neighbors in the predicted conformational C2-V3-C3 structure [41]. On the other hand, the Q366N C3 mutation was present in one of two patients in which IgG antibodies were not detected [50] and in several X4-tropic viruses that were resistant to neutralization by vaccination [40]. Effectively, this last position could play a supporting role in co-receptor interaction and was possibly also observed in an R5 cluster (Fig.…”

“…Furthermore, six immunogenic regions have been identified in the HIV-2 envelope glycoproteins. Three of them are in gp125 (amino acids 234 to 248 in C2, 296 to 337 in V3, and 472 to 507 in C5), and the others are in the ectodomain of gp36 (amino acids 573 to 595, 634 to 649, and 644 to 658) [42][43][44][45][46][47][48][49][50]. Recently, Barroso and his co-workers have shown that the HIV-2 C2 and C3 are well exposed in the envelope complex and are under strong diversifying selection [41].…”