According to a recent study, varicella and herpes zoster viruses utilize powerful immune evasion strategies to inhibit the ability of NK cells to destroy infected cells and to inhibit the production of molecules that help control viral infections. The results were published in the open access journal of PLOS Pathogens. Just as the authors point out, further research that elucidates potential molecular mechanisms may allow for the use of this knowledge in therapeutic settings, where abnormal NK cell activation can cause immunopathology, such as certain autoimmune diseases, transplanted immune rejection, etc.
NK cells are a type of white blood cell that helps control viral infection by killing infected cells and secreting molecules called pro-inflammatory cytokines to activate and direct the immune response. Viruses such as varicella zoster virus (VZV), which cause varicella and herpes zoster, suppress the immune system and cause infections in the human body. VZV can infect human natural killer cells, but does not know how or whether VZV can directly affect the function of NK cells. To solve this problem, Abendroth and her colleagues used human VZV-infected cells to culture human peripheral blood mononuclear cells and then assessed the function of NK cells.
The researchers found that VZV has a previously unreported strategy to effectively inhibit the function of NK cells and prevent natural killer cells from destroying infected cells and producing cytokines. The powerful damage of this function depends on direct contact between natural killer cells and VZV-infected cells. In this way, VZV causes NK cells to paralyze from a functional response to target cells. Herpes simplex virus type I is also effective in infecting NK cells and making natural killer cells unresponsive to target cell stimulation. These findings indicate for the first time that two human alpha herpesviruses directly evade immune responses against multiple antiviral functions of NK cells. The author of this study claimed that they have got a clearer understanding of how herpesviruses manipulate host immune responses.
- Campbell TM, McSharry BP, Steain M, Russell TA, Tscharke DC, Kennedy JJ, et al. (2019) Functional paralysis of human natural killer cells by alphaherpesviruses. PLOS Pathogens 15(6): e1007784. doi.org/10.1371/journal.ppat.1007784