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

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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 gp125C2-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.

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Acknowledgments

This work was financially supported by grants from the Italian Ministry of Instruction University & Research (MIUR), “Progetto FILAS”, and by the European Commission Framework 7 Programme (CHAIN, the Collaborative HIV and Anti-HIV Drug Resistance Network, Integrated Project no. 223131). We are thankful for Amalia Mastrofrancesco, Marzia Romani and Fabio Mercurio for their excellent technical assistance.

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  1. Virology, Department of Experimental Medicine and Biochemistry, Tor Vergata University, Via Montpellier 1, 00133, Rome, Italy

    Salvatore Dimonte, Valentina Svicher, Romina Salpini, Francesca Ceccherini-Silberstein, Carlo-Federico Perno & Muhammed Babakir-Mina

  2. National Institute of Infectious Diseases (INMI) ‘Lazzaro Spallanzani’, Rome, Italy

    Carlo-Federico Perno

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  1. Salvatore Dimonte
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Correspondence to Muhammed Babakir-Mina.

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705_2011_1075_MOESM1_ESM.pdf

Novel gp125 C2-V3-C3 mutations significantly associated with each other. aThe frequency was determined for 149 samples from HIV-2-infected patients, all with pure phenotype and/or co-receptor determinations known. bThe frequency was determined for 38 HIV-2 samples, all reported with pure X4-phenotype and/or co-receptor determinations. cPercentages were calculated for patients with each specific gp125 C3 or V3 mutation. dPositive and negative correlations with φ > 0.2 and φ < -0.2, respectively, are shown. e P values significant (P < 0.05) after correction for multiple hypothesis testing [58]. (PDF 56 kb)

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Dimonte, S., Svicher, V., Salpini, R. et al. HIV-2 A-subtype gp125C2-V3-C3 mutations and their association with CCR5 and CXCR4 tropism. Arch Virol 156, 1943–1951 (2011). https://doi.org/10.1007/s00705-011-1075-z

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