Highly complex neutralization determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India

Smita S. Kulkarni, Alan Lapedes, Haili Tang, S. Gnanakaran, Marcus G. Daniels, Ming Zhang, Tanmoy Bhattacharya, Ming Li, Victoria R. Polonis, Francine E. McCutchan, Lynn Morris, Dennis Ellenberger, Salvatore T. Butera, Robert C. Bollinger, Bette T. Korber, Ramesh S. Paranjape, David C. Montefiori

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)505-520
Number of pages16
JournalVirology
Volume385
Issue number2
DOIs
StatePublished - Mar 15 2009

Keywords

  • Envelope glycoproteins
  • Genetic signatures
  • HIV-1
  • Heatmap
  • Neutralizing antibodies

ASJC Scopus subject areas

  • Virology

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    Kulkarni, S. S., Lapedes, A., Tang, H., Gnanakaran, S., Daniels, M. G., Zhang, M., Bhattacharya, T., Li, M., Polonis, V. R., McCutchan, F. E., Morris, L., Ellenberger, D., Butera, S. T., Bollinger, R. C., Korber, B. T., Paranjape, R. S., & Montefiori, D. C. (2009). Highly complex neutralization determinants on a monophyletic lineage of newly transmitted subtype C HIV-1 Env clones from India. Virology, 385(2), 505-520. https://doi.org/10.1016/j.virol.2008.12.032