CD94 Is Essential for NK Cell-Mediated Resistance to a Lethal Viral Disease

It is well established that natural killer (NK) cells confer resistance to many viral diseases, but in only a few instances the molecular mechanisms whereby NK cells recognize virus-infected cells are known. Here we show that CD94, a molecule preferentially expressed by NK cells, is essential for the resistance of C57BL/6 mice to mousepox, a disease caused by the Orthopoxvirus ectromelia virus. Ectromelia virus-infected cells expressing the major histocompatibility complex (MHC) class Ib molecule Qa-1 b are specifically recognized by the activating receptor formed by CD94 and NKG2E. Because CD94-NKG2 receptors and their ligands are highly conserved in rodents and humans, a similar mechanism may exist during human infections with the smallpox and monkeypox viruses, which are highly homologous to ectromelia virus. [Display omitted] ► Deficiency in CD94 results in susceptibility to lethal mousepox ► NK cells require CD94 to protect from mousepox ► CD94-NKG2E recognizes ECTV-infected cells in a Qa-1 b-dependent manner