Biology Reference
In-Depth Information
4
Quantification of HIV/SIV Coreceptor
Expression
Benhur Lee and Robert W. Doms
Department of Pathology and Laboratory Medicine, University of
Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA
INTRODUCTION
Multiparametric ¯uorescence-activated cell sorter (FACS) analysis, including
the use of recently developed quantitative approaches, is assuming great im-
portance in the study of human immunode®ciency virus ( HIV )-1 infection as a
result of the fact that cellular entry by HIV-1 requires the sequential interaction
of the viral envelope protein (Env) with cell-surface CD4 and a coreceptor.
CCR5 and CXCR4, members of the chemokine receptor family, have been
identi®ed as the major coreceptors for viral entry (reviewed in Berger et al.,
1999; Doms and Peiper, 1997; Lee and Montaner, 1999). All HIV-1 isolates
studied to date use either one or both of these chemokine receptors for viral
entry (Doms et al., 1998). In general, macrophage-tropic strains of virus, pre-
dominantly isolated during the early stages of HIV infection and implicated in
sexual transmission of the virus, use CCR5 as a coreceptor. On the other hand,
T-cell tropic strains of virus, either T-cell line lab-adapted strains or those that
are more frequently isolated during progression to clinical disease, use CXCR4
as a coreceptor (reviewed in Husman and Schuitemaker, 1998). A signi®cant
minority of primary patient isolates is also able to use both CCR5 and CXCR4
as coreceptors. The importance of coreceptor usage for the paradigm of HIV
tropism is underscored by the new terminology in which viral strains are now
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