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

Abstract

The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and their cellular CD4-chemokine (CCR5/CXCR4) receptor complex. In this study, for the first time, the HIV-2 A-subtype gp125 C2-V3-C3 mutations and their tropism association were characterized by analyzing 149 HIV-2 sequences from the Los Alamos database. The analysis has strengthened the importance of C2-V3-C3 region as a determinant factor for co-receptor selection. Moreover, statistically significant correlations were observed between C2-V3-C3 mutations, and several correlated mutations were associated with CXCR4 and CCR5 co-receptor usage. A dendrogram showed two distinct clusters, with numerous associated mutations grouped, thus dividing CCR5-and CXCR4-tropic viruses. Fourteen X4-tropic virus mutations, all in V3 and C3 domains and forming highly significant subclusters, were found. Finally, R5 associations, two strong subclusters were observed, grouping several C2-V3-C3 mutated positions. These data indicate the possible contribution of C2-V3-C3 mutational patterns in regulating HIV-2 tropism.

Selected amino acid changes in HIV-1 subtype-C gp41 are associated with specific gp120V3 signatures in the regulation of co-receptor usage

“…The gp41 is a transmembrane glycoprotein that retains the gp120 on viral surface with non-covalent interactions (Helseth et al, 1991) and some studies indicate that several mutations in gp41 were involved to be significantly associated with co-receptor usage (Dimonte et al, 2011a;Huang et al, 2008;Stawiski et al, 2009;Thielen et al, 2009Thielen et al, , 2010, beyond the primary classical determinants of gp120 including particularly positions 11 and 25 in V3-loop (de Jong et al, 1992;Fouchier et al, 1992;Resch et al, 2001), and secondly by other flanking domains (as V1, V2, C3, C4 and V5) (Carrillo and Ratner, 1996;Huang et al, 2008Huang et al, , 2011Koito et al, 1995;Labrosse et al, 2001;Lin et al, 2011;Pastore et al, 2006;Svicher et al, 2011b;Suphaphiphat et al, 2007). Both CCR5 and CXCR4 co-receptors interact with the same region of the surface gp120 viral protein that encompasses not only the V3 loop but also specific regions from the V1/V2 and the C4 domains (Sierra et al, 2007).…”

“…mine a moderate increase of V3-loop antigenic index in HIV-1 472 B-subtype(Svicher et al, 2011b) that is probably resulting in a 473 more protruding V3-crown exposure. Using the same approach (Jameson-Wolf methodology), the mutation F20L V3 in HIV-1 Csubtype correlates with a decreased hydrophobicity and surface 476 probability (−0.11 and −0.05, respectively).…”

Genetic Variation and Evolution of the 2019 Novel Coronavirus

“…All amino acid viral sequences of the spike, nucleocapsid, membrane, and envelope proteins were screened in both animal and human viruses, and the frequency of mutations was calculated and statistically compared using the χ 2 test (based on a 2 × 2 contingency table containing the number of isolates from animal and human viruses and the number of isolates with and without mutations) [16, 17]. Fisher exact tests were used to determine whether the differences in frequency between the 2 groups of samples (animal vs. human) were statistically significant.…”

HIV-2 and its role in conglutinated approach towards Acquired Immunodeficiency Syndrome (AIDS) Vaccine Development

“…FHSQ and WCR are crucial targets for neutralizing antibodies. These motifs can play a vital role for the designing of a potential HIV-2 vaccine (Dimonte et al 2011; Morner et al 1999). …”