Adhesion and fusion efficiencies of human immunodeficiency virus type 1 (HIV-1) surface proteins

Sci Rep. 2013 Oct 22;3:3014. doi: 10.1038/srep03014.

Abstract

In about half of patients infected with HIV-1 subtype B, viral populations shift from utilizing the transmembrane protein CCR5 to CXCR4, as well as or instead of CCR5, during late stage progression of the disease. How the relative adhesion efficiency and fusion competency of the viral Env proteins relate to infection during this transition is not well understood. Using a virus-cell fusion assay and live-cell single-molecule force spectroscopy, we compare the entry competency of viral clones to tensile strengths of the individual Env-receptor bonds of Env proteins obtained from a HIV-1 infected patient prior to and during coreceptor switching. The results suggest that the genetic determinants of viral entry were predominantly enriched in the C3, HR1 and CD regions rather than V3. Env proteins can better mediate entry into cells after coreceptor switch; this effective entry capacity does not correlate with the bond strengths between viral Env and cellular receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4 Antigens / metabolism
  • Cell Line
  • HIV-1 / physiology*
  • Humans
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Receptors, CCR5 / metabolism
  • Receptors, CXCR4 / metabolism
  • Receptors, HIV / metabolism
  • Virus Attachment*
  • Virus Internalization*
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • CD4 Antigens
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, HIV
  • env Gene Products, Human Immunodeficiency Virus