Natural killer cell receptors in human immunodeficiency virus infection: pathways to protection or doors to disappointment?

In the absence of effective treatment, infection with the human immunodeficiency virus (HIV) ultimately leads to the acquired immune deficiency syndrome (AIDS). Many attempts have been made to prevent and attenuate HIV infection. While antiretroviral therapies for infected individuals have had great success, preventative and therapeutic vaccines focused on both humoral and cellular-mediated immunity have failed. Recently, several natural killer cell receptor (NKR) genotypes, in concert with certain class I human histompatibility-linked antigens (HLA) were found to be associated with protection from HIV infection and/or disease progression. These receptors are expressed on both natural killer (NK) cells and subsets of T lymphocytes. As HIV infection is often associated with attenuation of NK cells and much remains unknown about the basic functions of NKR, it remains undetermined whether the protective effect of these receptors relates to their expression on NK cells, T lymphocytes or both. This review summarizes current literature regarding NKR and HIV infection, and addresses several major questions remaining about the role of these receptors in protection against infection and disease progression.