HIV: cell binding and entry

Cold Spring Harb Perspect Med. 2012 Aug 1;2(8):a006866. doi: 10.1101/cshperspect.a006866.


The first step of the human immunodeficiency virus (HIV) replication cycle-binding and entry into the host cell-plays a major role in determining viral tropism and the ability of HIV to degrade the human immune system. HIV uses a complex series of steps to deliver its genome into the host cell cytoplasm while simultaneously evading the host immune response. To infect cells, the HIV protein envelope (Env) binds to the primary cellular receptor CD4 and then to a cellular coreceptor. This sequential binding triggers fusion of the viral and host cell membranes, initiating infection. Revealing the mechanism of HIV entry has profound implications for viral tropism, transmission, pathogenesis, and therapeutic intervention. Here, we provide an overview into the mechanism of HIV entry, provide historical context to key discoveries, discuss recent advances, and speculate on future directions in the field.

Publication types

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

MeSH terms

  • CD4 Antigens / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cell Transformation, Viral / physiology
  • HIV / immunology
  • HIV / pathogenicity*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / immunology*
  • Humans
  • Integrins / metabolism
  • Protein Binding
  • Receptors, CCR4 / metabolism
  • Receptors, CCR5 / metabolism
  • Signal Transduction / physiology
  • Virion / metabolism
  • env Gene Products, Human Immunodeficiency Virus / metabolism*


  • CD4 Antigens
  • HIV Envelope Protein gp120
  • Integrins
  • Receptors, CCR4
  • Receptors, CCR5
  • env Gene Products, Human Immunodeficiency Virus
  • integrin alpha4beta7