CD8 T cell control of HSV reactivation from latency is abrogated by viral inhibition of MHC class I

In humans, herpes simplex virus (HSV) establishes latency in sensory nerve ganglia from where it periodically reactivates, whereas in murine models, the virus efficiently establishes latency but rarely reactivates. HSV inhibits MHC class I antigen presentation to CD8 T cells efficiently in humans but poorly in mice, and whether this is a crucial determinant of HSV's ability to reactivate in humans remains uncertain. To test this, we generated a panel of recombinant HSVs that inhibit presentation by murine MHC class I mimicking the effect in humans. Antigen-specific CD8 T cells prevent the in vivo reactivation of wild-type HSV. Despite their presence in the ganglia of latently infected mice, CD8 T cells do not prevent the reactivation of recombinant HSVs that inhibit murine MHC class I in mice. These findings suggest that efficient inhibition of MHC class I by HSV is a key factor in its ability to reactivate in humans.