Hematopoietic stem cells (HSCs) are one of the few cell types able to resist infection with HIV-1 despite expressing the cell surface molecules to which HIV-1 binds before entering a cell. In a study that appears in the February issue of the Journal of Clinical Investigation, researchers from Harvard Medical School, Boston, show that HSC expression of a protein known as p21Waf1/Cip1/Sdi1 (p21) is required for HSCs to be resistant to infection with HIV-1.
David Scadden and colleagues showed that HSCs in which expression of p21 was decreased were more susceptible to infection with HIV-1 than cells expressing normal levels of p21. Further analysis showed that p21 did not inhibit HIV-1 entering the cells, rather it prevented the viral DNA integrating into the host cell genome by binding to the HIV-1 integrase complex and preventing it from mediating chromosomal integration. This protective mechanism was specific for HIV-1, as decreased expression of p21 in HSCs did not allow a related virus (SIVmac-251) to productively infect the HSCs. This study therefore identifies p21 as a protective factor that prevents HSCs being infected with HIV-1.
In an accompanying commentary, Paul D. Bieniasz from the Aaron Diamond AIDS Research Center, New York, discusses how this study adds p21 to an ever-growing list of cellular proteins that alter the sensitivity of a cell to infection with HV-1, but cautions that “it would seem premature to dub p21 a bona fide restriction factor.” (a protein whose major, and perhaps only, role is to prevent retrovirus replication).