Characterization of a chemokine receptor CCR5-negative T cell line and its use in determining human immunodeficiency virus type 1 phenotype.
A human CD4-positive T cell line from a donor homozygous negative for the chemokine receptor CCR5 was established, characterized, and used for determining the coreceptor usage of human immunodeficiency virus type 1 (HIV-1) isolates. Clones of this IL-2 dependent human T-cell lymphotropic virus type 1 (HTLV-I) immortalized cell line, named IsnoR5 clones 1 and 2, are susceptible to infection by HIV-1 isolates that use CXCR4 as a coreceptor but resistant to infection by CCR5 tropic HIV-1 viruses. HIV-1 isolates whose replication is inhibited in IsnoR5 cells in the presence of the bicyclam AMD 3100, a CXCR4 specific inhibitor, utilize a coreceptor distinct from CCR5 and CXCR4. Using a panel of primary HIV-1 isolates we have shown that a single T cell line is sufficient to discriminate between use of CCR5, CXCR4 or an alternative coreceptor. As IsnoR5 clone 1 cells revealed the existence of even minor populations of CXCR4-using virus variants, they could be useful for the early identification of changes in coreceptor usage in HIV infected individuals facilitating the timely introduction of appropriate clinical treatments.
D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification* / Q000254:growth & development; D015368:Human T-lymphotropic virus 1 / Q000502:physiology; D006801:Humans; D019713:Receptors, CCR5 / Q000172:deficiency*; D015728:Receptors, HIV / Q000172:deficiency*
D019713:Receptors, CCR5; D015728:Receptors, HIV