CD4+ NK cells can be productively infected with HIV, leading to downregulation of CD4 expression and changes in function.
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-1alpha 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.
Bernstein
Helene B
HB
Department of Reproductive Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. hbb22@case.edu
Wang
Guangwu
G
Plasterer
Mary C
MC
Zack
Jerome A
JA
Ramasastry
Parthasarathy
P
Mumenthaler
Shannon M
SM
Kitchen
Christina M R
CM
D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D019713:Receptors, CCR5 / Q000378:metabolism*
D015704:CD4 Antigens; D019713:Receptors, CCR5