A predictive model for HIV type 1 coreceptor selectivity

AIDS Res Hum Retroviruses. 2013 Oct;29(10):1386-94. doi: 10.1089/AID.2012.0173. Epub 2013 Jul 30.

Abstract

Despite its sequence variability and structural flexibility, the V3 loop of the HIV-1 envelope glycoprotein gp120 is capable of recognizing cell-bound coreceptors CCR5 and CXCR4 and infecting cells. Viral selection of CCR5 is associated with the early stages of infection, and transition to selection of CXCR4 indicates disease progression. We have developed a predictive statistical model for coreceptor selectivity that uses the discrete property of net charge and the binary coreceptor preference markers of the N(6)X(7)[T/S](8)X(9) glycosylation motif and 11/24/25 positive amino acid rule. The model is based on analysis of 2,054 V3 loop sequences from patient data and allows us to infer the most likely state of the disease from physicochemical characteristics of the sequences. The performance of the model is comparable to established sequence-based predictive methods, and may be used in combination with other methods as a supportive diagnostic for coreceptor selection. This model may be used for personalized medical decisions in administering coreceptor-specific therapies.

Publication types

  • Evaluation Study

MeSH terms

  • Computational Biology / methods*
  • Disease Progression
  • HIV Envelope Protein gp120 / genetics*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / diagnosis
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / physiology
  • Humans
  • Molecular Diagnostic Techniques / methods*
  • Receptors, HIV / metabolism*
  • Virus Attachment*

Substances

  • HIV Envelope Protein gp120
  • Receptors, HIV
  • gp120 protein, Human immunodeficiency virus 1