The Macrophage in HIV-1 Infection and Disease Progression
Paul R. Gorry, Jasminka Sterjovski and Melissa J. Churchill
from: Lentiviruses and Macrophages: Molecular and Cellular Interactions (Edited by: Moira Desport). Caister Academic Press, U.K. (2010)
Rapid depletion of CD4+ T-lymphocytes has been associated with a switch in HIV-1 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. HIV-1 disease progression is associated with an enhanced tropism of R5 viral strains for cells of the monocyte/macrophage lineage (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 chapter 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 may result from adaptive viral evolution, resulting in HIV-1 variants that have increased ability to utilize relatively low levels of CD4 and CCR5 expressed on macrophages. 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, particularly in patients who persistently harbour only R5 viral strains read more ...