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[摘要]：The gamma(1)34.5 protein of herpes simplex viruses (HSV) is essential for virulence. Accordingly, an HSV mutant lacking gamma(1)34.5 is attenuated in vivo. Despite its vaccine potential, the mechanism by which the gamma(1)34.5 null mutant triggers protective immunity is unknown. In this report we show that vaccination with the gamma(1)34.5 null mutant protects against lethal challenge from wild-type virus via I kappa B kinase in dendritic cells (DCs), which sense virus-associated molecular patterns. Unlike mock-treated DCs, DCs primed with the gamma(1)34.5 null mutant ex vivo mediate resistance to wild-type HSV after adoptive transfer into niave mice. Furthermore, the gamma(1)34.5 null mutant activates I kappa B kinase, which facilitates p65/RelA phosphorylation and nuclear translocation, resulting in DC maturation. While unable to produce infectious virus in DCs, this mutant virus expresses early and late genes. In its abortive infection, the gamma(1)34.5 null mutant induces protective immunity more effectively in CD8(+) DCs than in CD8(-) DCs. This is mirrored by a higher level of interleukin-6 (IL-6) and IL-12 secretion by CD8(+) DCs than CD8(-) DCs. Remarkably, inhibition of p65/RelA phosphorylation or nuclear translocation in CD8(+) DCs disrupts protective immunity. These results suggest that engagement of the gamma(1)34.5 null mutant with CD8(+) DCs elicits innate immunity to activate NF-kappa B, which translates into protective immunity. |
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