CXCR4 as a functional coreceptor for human immunodeficiency virus type 1 infection of primary macrophages

G Simmons1, J D Reeves, A McKnight

  • 1Section of Virology, Chester Beatty Laboratories, Institute of Cancer Research, London SW3 6JB, United Kingdom.

Journal of Virology
|September 12, 1998
PubMed

Insights

Primary human immunodeficiency virus type 1 (HIV-1) strains utilize CXCR4 and CCR5 coreceptors for macrophage infection. While CXCR4 is sufficient, some strains also use CCR5, with AMD3100 inhibiting infection.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) entry into host cells requires coreceptors.
  • Syncytium-inducing (SI) HIV-1 strains infect various cell types, including macrophages.
  • The specific coreceptors utilized by SI HIV-1 for macrophage infection are not fully elucidated.

Purpose of the Study:

  • To investigate the coreceptors used by primary syncytium-inducing (SI) HIV-1 isolates for infection of primary macrophages.
  • To determine the role of CXCR4 and CCR5 in SI HIV-1 macrophage tropism.
  • To assess the impact of coreceptor usage on viral replication efficiency.

Main Methods:

  • Infection of primary macrophages with SI HIV-1 isolates.
  • Assessment of viral replication in macrophages with varying CCR5 expression levels.
  • Inhibition studies using CXCR4 ligands, including AMD3100.

Main Results:

  • SI HIV-1 strains utilizing only CXCR4 replicated efficiently in macrophages regardless of CCR5 expression.
  • These CXCR4-dependent strains were inhibited by CXCR4 ligands like AMD3100.
  • SI strains using multiple coreceptors (including CCR5) showed reduced infection efficiency in CCR5-deficient macrophages and were inhibited by AMD3100.

Conclusions:

  • CXCR4 is a crucial coreceptor for SI HIV-1 infection of primary macrophages.
  • CCR5 can also be utilized by certain SI HIV-1 strains, but it is not essential when CXCR4 is available.
  • These findings provide no evidence for the use of alternative coreceptors beyond CXCR4 and CCR5 in this context.

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