Detecting and understanding genetic and structural features in HIV-1 B subtype V3 underlying HIV-1 co-receptor usage

Mengjie Chen, Valentina Svicher, Anna Artese, Giosué Costa, Claudia Alteri, Francesco Ortuso, Lucia Parrotta, Yang Liu, Chang Liu, Carlo Federico Perno, Stefano Alcaro, Jing Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Motivation: To define V3 genetic elements and structural features underlying different HIV-1 co-receptor usage in vivo. Results: By probabilistically modeling mutations in the viruses isolated from HIV-1 B subtype patients, we present a unique statistical procedure that would first identify V3 determinants associated with the usage of different co-receptors cooperatively or independently, and then delineate the complicated interactions among mutations functioning cooperatively. We built a model based on dual usage of CXCR4 and CCR5 co-receptors. The molecular basis of our statistical predictions is further confirmed by phenotypic and molecular modeling analyses. Our results provide new insights on molecular basis of different HIV-1 co-receptor usage. This is critical to optimize the use of genotypic tropism testing in clinical practice and to obtain molecular-implication for design of vaccine and new entry-inhibitors.

Original languageEnglish
Pages (from-to)451-460
Number of pages10
JournalBioinformatics
Volume29
Issue number4
DOIs
Publication statusPublished - Feb 15 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability
  • Medicine(all)

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