The biology of CCR5 and CXCR4

Curr Opin HIV AIDS. 2009 Mar;4(2):96-103. doi: 10.1097/COH.0b013e328324bbec.

Abstract

Purpose of review: We discuss the current knowledge concerning the biology of CXCR4 and CCR5 and their roles in HIV-1 infection.

Recent findings: Important research findings reported in the last 2 years have advanced our knowledge in the field of HIV coreceptors and pathogenesis. Novel methods have been used to crystallize two new members of the G-protein coupled receptors. It has been demonstrated that expression and stability of the naturally occurring truncated CCR5 protein is critical for resistance to HIV-1. The first stem cell transplantation of donor cells with the CCR5 mutation provided proof of principle. The Food and Drug Administration approved the first CCR5-based entry inhibitor. New CXCL12 isoforms were discovered, one isoform is a potent X4 inhibitor with weak chemotaxis activity.

Summary: The coreceptor discoveries revealed new insights into host and viral factors influencing HIV transmission and disease. The HIV/coreceptor interaction has become a major target for the development of novel antiviral strategies to treat and prevent HIV infection. The first CCR5-based entry inhibitor has been recently approved. New drugs that promote CCR5 and CXCR4 internalization, independent of cellular signaling, might provide clinical benefits with minimum side effects.

Publication types

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

MeSH terms

  • Anti-HIV Agents / pharmacology
  • HIV Fusion Inhibitors / pharmacology
  • HIV-1 / physiology
  • Protein Structure, Tertiary
  • Receptors, CCR5 / chemistry
  • Receptors, CCR5 / drug effects
  • Receptors, CCR5 / physiology*
  • Receptors, CXCR4 / chemistry
  • Receptors, CXCR4 / drug effects
  • Receptors, CXCR4 / physiology*
  • Receptors, HIV / chemistry
  • Receptors, HIV / drug effects
  • Receptors, HIV / physiology
  • Virus Internalization

Substances

  • Anti-HIV Agents
  • HIV Fusion Inhibitors
  • Receptors, CCR5
  • Receptors, CXCR4
  • Receptors, HIV