Proliferative activation up-regulates expression of CD4 and HIV-1 co-receptors on NK cells and induces their infection with HIV-1.

NK cells play important roles in immune surveillance against malignancy and virus-infected cells. NK cell functions are affected in patients infected with HIV-1; however, whether there is direct interaction between NK cells and HIV-1 remains controversial. In this study the expression of CD4, an important receptor for HIV-1, was up-regulated on NK cells co-cultured with an NK cell-selective stimulating cell line, HFWT, and rIL-2. Although the level of CD4 was lower on NK cells than on CD4+ T cells, expression of the HIV-1 co-receptor CCR5 was clearly up-regulated on CD4+ NK cells. CD4+ NK cells expressed higher levels of HLA-DR and CD25 than CD4- NK cells, suggesting that they were highly activated. Cell-free HIV-1 could not infect the NK cells, but NK cells were infected when co-cultured with HIV-1-infected T cells. Using this co-culture system, we can better understand how HIV-1 infects NK cells and how NK cell functions are affected in AIDS.