Role for latent herpesvirus infection in NK-cell arming. The data presented by White et al suggest a model in which naive NK cells in mice can be induced to become armed lytic effectors by latent infection with MuHV-4. Murine NK cells typically exist under pathogen free conditions in an unarmed state without high-level expression of granzyme B and perforin. While it is unclear in what state of maturity lytic granules may be formed in unarmed NK cells, granzyme A is expressed, but morphologic assessments define a lack of fully matured granules.³  Presumably, after an acute infection (green arrows), an armed NK cell will participate in killing and either end its lifecycle via death or revert to a less armed state but persist as a memory NK cell. These latter cells do not appear armed, but retain potential to more actively participate in immune responses.^12,13  The data suggest that unlike acute infection, latent infection is capable of not only arming NK cells, but maintaining them in an armed state (purple arrows). Since human NK cells are typically armed at baseline, this raises a role for latent infection or similar signals in enabling their continually armed state. While the mechanism of how latent infection promotes arming is unclear, the majority of armed cells in a latently infected host would not be fighting active infection and degranulating. Therefore, in the case of latent infection, it would be predicted that many will continue to persist in an armed state, and not simply progressing to death or memory-like phenotypes. Without latent infection or similar signals derived from other environmental challenges (such as in SPF mice), the majority of NK cells will exist in the naive state. This is therefore not seen in humans, as environmental challenges and latent herpesviral infections are ubiquitous. Professional illustration by Paulette Dennis.