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HIV disease: fallout from a mucosal catastrophe?

Jason M Brenchley1, David A Price, Daniel C Douek

  • 1Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Nature Immunology
|February 17, 2006
PubMed
Summary

Human immunodeficiency virus (HIV) rapidly destroys CD4(+) T cells at mucosal surfaces, not just gradually in blood. This early depletion explains chronic HIV disease aspects previously misunderstood.

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Area of Science:

  • Immunology
  • Virology
  • Pathogenesis

Background:

  • The traditional view of human immunodeficiency virus (HIV) pathogenesis focuses on gradual CD4(+) T cell depletion in peripheral blood.
  • Recent studies reveal rapid CD4(+) T cell loss at mucosal surfaces in simian immunodeficiency virus (SIV)- and HIV-infected individuals.

Purpose of the Study:

  • To re-evaluate HIV disease models based on new findings of rapid mucosal CD4(+) T cell depletion.
  • To propose a hypothesis explaining chronic phase disease characteristics linked to early mucosal immune assault.

Main Methods:

  • Review and synthesis of existing studies on SIV and HIV infection in macaques and humans.
  • Development of a theoretical model integrating mucosal immunology with HIV pathogenesis.

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Main Results:

  • HIV infection causes substantial, rapid CD4(+) T cell depletion at mucosal sites, which are reservoirs for these immune cells.
  • The extent of mucosal CD4(+) T cell loss is not accurately represented by peripheral blood counts.

Conclusions:

  • Early and severe depletion of mucosal CD4(+) T cells is a critical factor in HIV pathogenesis.
  • This mucosal damage likely drives key aspects of chronic HIV disease, necessitating a revised understanding of the infection's progression.