R5 HIV env and vesicular stomatitis virus G protein cooperate to mediate fusion to naive CD4+ T Cells

J Virol. 2011 Jan;85(1):644-8. doi: 10.1128/JVI.01851-10. Epub 2010 Oct 27.

Abstract

Naïve CD4(4) T cells are resistant to both HIV R5 env and vesicular stomatitis virus G protein (VSV-G)-mediated fusion. However, viral particles carrying both HIV R5 env and VSV-G infect naïve cells by an unexplained mechanism. We show that VSV-G-pseudotyped virus cannot fuse to unstimulated cells because the viral particles cannot be endocytosed. However, virions carrying both HIV R5 env and VSV-G can fuse because CD4 binding allows viral uptake. Our findings reveal a unique mechanism by which R5 HIV env and VSV-G cooperate to allow entry to naïve CD4(+) T cells, providing a tool to target naïve CD4(+) T cells with R5 HIV to study HIV coreceptor signaling and latency.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes / virology*
  • HIV-1 / genetics
  • HIV-1 / metabolism
  • Humans
  • Membrane Fusion*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Receptors, CCR5 / metabolism
  • Vesicular stomatitis Indiana virus / genetics
  • Vesicular stomatitis Indiana virus / metabolism
  • Vesicular stomatitis Indiana virus / pathogenicity
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Virion / genetics
  • Virion / metabolism*
  • Virus Internalization*
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / metabolism*

Substances

  • G protein, vesicular stomatitis virus
  • Membrane Glycoproteins
  • Receptors, CCR5
  • Viral Envelope Proteins
  • env Gene Products, Human Immunodeficiency Virus