Natural Killer cells in viral infections: Clinical implications and therapeutic intervention

Abstract

Natural Killer (NK) cells, a subset of lymphocytes characterized by the expression of CD56 and the lack of CD3, are important effector cells of the innate immune system and provide a first-line defense against viruses. NK cells express both activating and inhibiting receptors, and the combined input of the receptors determines activation of the cell. For a long time, killing of cells that express a reduced level of MHC complexes such as tumor cells and virally infected cells was considered to be the major function of NK cells. Recent studies have suggested additional functions for NK cells. It was shown that NK cells have an important regulatory role in the initiation, progression and termination of an immune response. Furthermore, various discoveries have led to the hypothesis that the NK cell represents an evolutionary bridge between the innate and adaptive immune system. During evolution, many viruses have developed numerous strategies to escape NK cells, which highlights the importance of NK cells in the protection against viruses. The majority of the viruses utilize MHC-I mimicry/up-regulation/redistribution, down-regulation of NK activating ligands or interference with interferon signaling as NK cell inhibiting strategies. Viruses form a continuous threat to humans, due to their ability to mutate frequently. Studying the escape mechanisms of viruses may provide a basis to identify targets that can be addressed therapeutically so that specifically NK cell immunity is enhanced. With the newly discovered innate and adaptive abilities of NK cells, targeting NK cells may stimulate both parts of the immune system, resulting in more efficient anti-viral immune responses. This report will review the recently discovered regulatory role of NK cells, and it will focus on the interaction of NK cells with viruses to survey potential targets for therapeutic intervention.