TY - JOUR
T1 - Highly complex neutralization determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India
AU - Kulkarni, Smita S.
AU - Lapedes, Alan
AU - Tang, Haili
AU - Gnanakaran, S.
AU - Daniels, Marcus G.
AU - Zhang, Ming
AU - Bhattacharya, Tanmoy
AU - Li, Ming
AU - Polonis, Victoria R.
AU - McCutchan, Francine E.
AU - Morris, Lynn
AU - Ellenberger, Dennis
AU - Butera, Salvatore T.
AU - Bollinger, Robert C.
AU - Korber, Bette T.
AU - Paranjape, Ramesh S.
AU - Montefiori, David C.
N1 - Funding Information:
We gratefully acknowledge the staff of the “Acute Pathogenesis of HIV-1 Infection” project, National AIDS Research Institute, Pune, India who helped in collecting the samples and in generating the data. This work was funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH) (AI30034) and by the Bill and Melinda Gates Foundation (#38619). This work was also supported in part by NIAID, NIH (AI 33879-02), NIH-NCRR OPD-GCRC (5M01RR00722), the NIH-Fogarty International Center (D43TW0000), and intramural research grants from the Indian Council of Medical Research.
PY - 2009/3/15
Y1 - 2009/3/15
N2 - Little is known about the neutralization properties of HIV-1 in India to optimally design and test vaccines. For this reason, a functional Env clone was obtained from each of ten newly acquired, heterosexually transmitted HIV-1 infections in Pune, Maharashtra. These clones formed a phylogenetically distinct genetic lineage within subtype C. As Env-pseudotyped viruses the clones were mostly resistant to IgG1b12, 2G12 and 2F5 but all were sensitive to 4E10. When compared to a large multi-subtype panel of Env-pseudotyped viruses (subtypes B, C and CRF02_AG) in neutralization assays with a multi-subtype panel of HIV-1-positive plasma samples, the Indian Envs were remarkably complex. With the exception of the Indian Envs, results of a hierarchical clustering analysis showed a strong subtype association with the patterns of neutralization susceptibility. From these patterns we were able to identify 19 neutralization cluster-associated amino acid signatures in gp120 and 14 signatures in the ectodomain and cytoplasmic tail of gp41. We conclude that newly transmitted Indian Envs are antigenically complex in spite of close genetic similarity. Delineation of neutralization-associated amino acid signatures provides a deeper understanding of the antigenic structure of HIV-1 Env.
AB - Little is known about the neutralization properties of HIV-1 in India to optimally design and test vaccines. For this reason, a functional Env clone was obtained from each of ten newly acquired, heterosexually transmitted HIV-1 infections in Pune, Maharashtra. These clones formed a phylogenetically distinct genetic lineage within subtype C. As Env-pseudotyped viruses the clones were mostly resistant to IgG1b12, 2G12 and 2F5 but all were sensitive to 4E10. When compared to a large multi-subtype panel of Env-pseudotyped viruses (subtypes B, C and CRF02_AG) in neutralization assays with a multi-subtype panel of HIV-1-positive plasma samples, the Indian Envs were remarkably complex. With the exception of the Indian Envs, results of a hierarchical clustering analysis showed a strong subtype association with the patterns of neutralization susceptibility. From these patterns we were able to identify 19 neutralization cluster-associated amino acid signatures in gp120 and 14 signatures in the ectodomain and cytoplasmic tail of gp41. We conclude that newly transmitted Indian Envs are antigenically complex in spite of close genetic similarity. Delineation of neutralization-associated amino acid signatures provides a deeper understanding of the antigenic structure of HIV-1 Env.
KW - Envelope glycoproteins
KW - Genetic signatures
KW - HIV-1
KW - Heatmap
KW - Neutralizing antibodies
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U2 - 10.1016/j.virol.2008.12.032
DO - 10.1016/j.virol.2008.12.032
M3 - Article
C2 - 19167740
AN - SCOPUS:60749124402
SN - 0042-6822
VL - 385
SP - 505
EP - 520
JO - Virology
JF - Virology
IS - 2
ER -