| |
Infection of Natural Killer Cells by R5 and X4 HIV-1 Strains A. VALENTIN*, D. PATENAUDE, and G. N. PAVLAKIS.
BRL NCI-FCRDC, Frederick, MD Impairment of natural immunity, including decreased cytotoxic activity by NK cells, is a common feature of HIV-1 infected individuals. To identify the reasons for these defects, we have examined the expression of HIV receptors and susceptibility to infection of primary human NK cells.
Using a three-color flow cytometry assay we have found that a subset of uncultered primary CD56+ (NK) cells express CCR5 and CXCR4, the main HIV-1 coreceptors, as well as CD4. Infection studies with GFP-tagged HIV-1 molecular clones demonstrate that NK cells are targets for both R5 and X4 restricted HIV-1 strains, as judged by GFP and p24 production of CD56+CD3+ and CD56+CD3- primary cells. The proportion of infected CD56+ cells increased over time after infection with either X4 or R5 viruses.
HIV-1 infection of PBMC results in depletion of CD3+T-lymphocytes and concomitant expansion of CD56+ cells, which become very important to maintain chronic viral infection in vitro. HIV-1 infected NK cells appear to be more resistant to the cytopathic effects of HIV as judged by the longer half-life of the infected CD56+ cells compared to the T-lymphocytes present in the same sample.
In agreement with these in vitro observations, we have found expansion of CD56+ cells with specific depletion of the CD56+CD4+ subset, in blood samples from HIV-1 infected patients with different severity of immunodeficiency.
These results suggest that NK cells can be targets for HIV infection. Defects in natural immunity present in HIV infected patients may be the result of direct effects of the virus on NK cells. The relative resistance of NK cells to the cytopathic effect of HIV suggests that these cells may be relevant to the maintenance of chronic infection even in patients under HAART.
Key Words: CCR5 CXCR4, CD56, NK cells
|
