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CD4+ NK cells can be productively infected with HIV, leading to downregulation of CD4 expression and changes in function |
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| Authors: | Helene B. Bernstein Guangwu Wang Jerome A. Zack Shannon M. Mumenthaler |
| Affiliation: | a Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA b Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA c Departments of Medicine, Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA d Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA e Department of Biostatistics, School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA |
| Abstract: | NK cells mediate the innate immune response, and HIV-infected individuals demonstrate altered NK cell phenotype and function. We find that CD4+ NK cells are susceptible to HIV infection; this could account for the NK cell dysfunction seen in HIV-infected individuals. CD4+ NK cells express CXCR4 and can be infected with X4-tropic viruses and some primary R5-utilizing viral isolates. Treatment with the CXCR4 ligands AMD3100 and SDF-1α partially blocks infection with X4-tropic virus, treatment with anti-CCL Igs upregulates CCR5 surface expression and enables infection with HIV-Bal. HIV infection of NK cells results in CD4 downregulation and the production of infectious virus. HIV-infected CD4+ NK cells mediate NK cell cytotoxicity, however, HIV infection is associated with decreased chemotaxis towards IL-16. Thus, HIV infection of CD4+ NK cells could account for the NK cell dysfunction observed in HIV-infected individuals. Furthermore infected NK cells could serve as a viral reservoir of HIV in vivo. |
| Keywords: | NK cells HIV CD4 expression CD4 downregulation Chemotaxis |
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