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From the Aaron Diamond AIDS Research Center and The Rockefeller University, New York, 10016
Recent studies have identified several coreceptors that are required for fusion and entry of Human Immunodeficiency Virus type 1 (HIV-1) into CD4+ cells. One of these receptors, CCR5,
serves as a coreceptor for nonsyncytium inducing (NSI), macrophage-tropic strains of HIV-1, while another, fusin or CXCR-4, functions as a coreceptor for T cell line-adapted, syncytiuminducing (SI) strains. Using sequential primary isolates of HIV-1, we examined whether viruses
using these coreceptors emerge in vivo and whether changes in coreceptor use are associated
with disease progression. We found that isolates of HIV-1 from early in the course of infection
predominantly used CCR5 for infection. However, in patients with disease progression, the
virus expanded its coreceptor use to include CCR5, CCR3, CCR2b, and CXCR-4. Use of
CXCR-4 as a coreceptor was only seen with primary viruses having an SI phenotype and was
restricted by the env gene of the virus. The emergence of variants using this coreceptor was associated with a switch from NSI to SI phenotype, loss of sensitivity to chemokines, and decreasing CD4+ T cell counts. These results suggest that HIV-1 evolves during the course of infection to use an expanded range of coreceptors for infection, and that this adaptation is
associated with progression to AIDS.
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