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Journal of Virology, November 2004, p. 12288-12296, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12288-12296.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

CXCR4-Dependent Infection of CD8⁺, but Not CD4⁺, Lymphocytes by a Primary Human Immunodeficiency Virus Type 1 Isolate

Department of Pediatrics and Molecular Virology, Immunology and Medical Genetics, Children's Research Institute and Ohio State University Medical Center, Columbus,¹ Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, Ohio²

Received 26 April 2004/ Accepted 9 July 2004

We recently isolated from an infant an X4-syncytium-inducing (SI) human immunodeficiency virus type 1 (HIV-1) variant (92US143-T8) that was able to infect CD8⁺ lymphocytes independently of CD4. Although it was CD4 independent, the 92US143-T8 isolate also maintained the ability to infect CD4⁺ cells. In the present study, we investigated the role of CXCR4 in the infection of CD4⁺ and CD8⁺ cells by this primary isolate. The expression of CXCR4 was down modulated in CD8⁺ lymphocytes after infection with the 93US143-T8 isolate. Infection of CD8⁺ lymphocytes by the 93US143-T8 isolate was prevented by treatment with AMD3100, a specific antagonist for CXCR4, indicating CXCR4-dependent infection. Interestingly, AMD3100 treatment had no inhibitory role in the infection of purified CD4⁺ lymphocytes by the same isolate. Furthermore, AMD3100 treatment failed to prevent infection of known CD4⁺ CXCR4⁺ T-cell lines (MT-2 and CEM) by the 93US143-T8 isolate. In fact, virus replication in the CD4⁺ cells was often enhanced in the presence of AMD3100. Viruses produced from the infected CD4⁺ cells in the presence of AMD3100 maintained an unchanged envelope genotype and an SI phenotype. For the first time, these results provide evidence of CXCR4-dependent infection of CD8⁺ lymphocytes by a primary HIV-1 isolate. This study also shows a different mode of infection for the CD4⁺ and CD8⁺ lymphocytes by the same HIV-1 variant. Finally, our findings suggest that a more careful evaluation is necessary before the random use of AMD3100 as a new entry inhibitor in patients harboring SI HIV-1 strains.