Mar 20, 2002

How does HIV cause depletion of CD4 lymphocytes? A mechanism involving virus signaling through its cellular receptors

Current Molecular Medicine
Miles W CloydL Wang

Abstract

HIV infection causes an acquired immunodeficiency, principally because of depletion of CD4 lymphocytes. The mechanism by which the virus depletes these cells, however, is not clearly understood. Since the virus predominantly infects CD4 lymphocytes in vivo, some have assumed that HIV replication directly kills the infected cells or that the anti-HIV immune response destroys them. However, a large number of studies do not support this concept. Rather, the data strongly indicate that CD4 lymphocyte depletion is by an indirect mechanism. Several theories on various direct and indirect mechanisms are reviewed. The most plausible mechanism, which is backed by in vivo data, involves the consequences of HIV contact with resting CD4 lymphocytes, which cannot support virus replication. HIV binding to, and signaling through, CD4 and chemokine receptor molecules on resting CD4 lymphocytes and other cell types [which extensively occurs as the rare, productively infected cells (ie: infected cells producing virus) migrate among other cells through the lymphoid tissues back into the blood] induces upregulation of L-selectin and Fas. When these resting, HIV-signaled CD4 cells return to the blood, they home very rapidly back to peripheral lymph...Continue Reading

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Mentioned in this Paper

Receptors, HIV
Immune Response
T-Lymphocyte
Immunologic Deficiency Syndromes
Circulatory System
Lymphopenia
Cardiovascular System
Bone Marrow
Viral Pathogenesis
Virus Replication

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