Publications & Reports

The role of viral coreceptors and enhanced macrophage tropism in human immunodeficiency virus type 1 disease progression.

Gorry PR, Sterjovski J, Churchill M, Witlox K, Gray L, Cunningham A, Wesselingh S
Macfarlane Burnet Institute for Medical Research and Public Health, Australia. [email protected]

Abstract

Despite numerous studies on the impact of viral diversity, human immunodeficiency virus type 1 (HIV-1)-specific immune responses and host factors on disease progression, we still do not have a firm understanding of the long-term pathogenesis of HIV-1 infection.

Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in viral coreceptor usage from CCR5 to CXCR4 in approximately 40 to 50% of infected individuals.

However, the majority of infected individuals who progress to AIDS harbour only CCR5-dependent (R5) viral strains.

The progression of HIV-1 disease is associated with an enhanced tropism of R5 viral strains for monocyte/macrophage lineage cells (enhanced M-tropism).

However, the underlying molecular mechanisms contributing to enhanced M-tropism by R5 HIV-1 strains, and how HIV-1 variants with enhanced M-tropism cause CD4+ T-cell depletion in vivo are unknown.

This review examines the relationship between viral coreceptor usage, M-tropism, and pathogenicity of HIV-1.

We highlight evidence supporting the hypothesis that enhanced M-tropism of R5 HIV-1 results from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilise relatively low levels of CCR5 expressed on macrophages, by way of increased CCR5 affinity.

The evidence also suggests that these late-emerging, R5 viral strains have reduced sensitivity to entry inhibitors, and increased ability to cause CD4+ T-lymphocyte loss.

These variants are likely to impact HIV-1 disease progression, especially in patients who persistently harbour only R5 viral strains.

Publication

  • Journal: Sexual Health
  • Published: 01/01/2004
  • Volume: 1
  • Issue: 1
  • Pagination: 23-34

Health Issue