Connor RI, Sheridan K, Ceradini D, Landau N; Aaron Diamond AIDS Research Center, New York, NY.
Using sequential primary isolates of HIV-1 from three infected individuals, we examined co-receptor requirements and determined whether changes in coreceptor use are associated with disease progression. We found that isolates of HIV-1 from early in the course of infection used predominantly CCR5 for infection. However, in patients with disease progression, the virus expanded it's co-receptor use to include CCR5, CCR3, CCR2b and fusin. Use of fusin as a co-receptor 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 co-receptor 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 co-receptors for infection and that this adaptation is associated with progression to AIDS.
Keywords: AEGIS, HIV-1, Disease Progression, Receptors, CXCR4, CD4 Lymphocyte Count, Acquired Immunodeficiency Syndrome, Chemokines, T-Lymphocytes, Human, AIDS
