Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1

J Virol. 2005 Oct;79(19):12132-47. doi: 10.1128/JVI.79.19.12132-12147.2005.

Abstract

The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs) function as a trimer, mediating virus entry by promoting the fusion of the viral and target cell membranes. HIV-1 Env trimers induce membrane fusion through a pH-independent pathway driven by the interaction between an Env trimer and its cellular receptors, CD4 and CCR5/CXCR4. We studied viruses with mixed heterotrimers of wild-type and dominant-negative Envs to determine the number (T) of Env trimers required for HIV-1 entry. To our surprise, we found that a single Env trimer is capable of supporting HIV-1 entry; i.e., T = 1. A similar approach was applied to investigate the entry stoichiometry of envelope glycoproteins from amphotropic murine leukemia virus (A-MLV), avian sarcoma/leukosis virus type A (ASLV-A), and influenza A virus. When pseudotyped on HIV-1 virions, the A-MLV and ASLV-A Envs also exhibit a T = 1 entry stoichiometry. In contrast, eight to nine influenza A virus hemagglutinin trimers function cooperatively to achieve membrane fusion and virus entry, using a pH-dependent pathway. The different entry requirements for cooperativity among Env trimers for retroviruses and influenza A virus may influence viral strategies for replication and evasion of the immune system.

Publication types

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

MeSH terms

  • Avian Sarcoma Viruses / physiology
  • Cell Line
  • HIV-1 / physiology*
  • Humans
  • Influenza A virus / physiology
  • Leukemia Virus, Murine / physiology
  • Membrane Fusion
  • Mutation
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics*
  • Viral Envelope Proteins / physiology*

Substances

  • Viral Envelope Proteins