Vaccinia virus lacking the Bcl-2-like protein N1 induces a stronger natural killer cell response to infection

The vaccinia virus (VACV) N1 protein is an intracellular virulence factor that has a Bcl-2-like structure and inhibits both apoptosis and signalling from the interleukin 1 receptor, leading to nuclear factor kappa 8 activation. Here, we investigated the immune response to intranasal infection with a virus lacking the N1 L gene (v Delta N1L) compared with control viruses expressing N1L. Data presented show that deletion of N1L did not affect the proportion of CD4(+) and CD8(+) T cells infiltrating the lungs or the cytotoxic T-cell activity of these cells. However, v Delta N1L induced an increased local natural killer cell activity between days 4 and 6 post-infection. In addition, in the absence of N1 the host inflammatory infiltrate was characterized by a reduced proportion of lymphocytes bearing the early activation marker CD69. Notably, there was a good correlation between the level of CD69 expression and weight loss. The implications of these findings are discussed.