Immune Control of -Herpesviruses.

Vaccination against -herpesviruses has been hampered by our limited understanding of their normal control. Epstein-Barr virus (EBV)-transformed B cells are killed by viral latency antigen-specific CD8 T cells , but attempts to block B cell infection with antibody or to prime anti-viral CD8 T cells have protected poorly . The Doherty laboratory used Murid Herpesvirus-4 (MuHV-4) to analyze -herpesvirus control in mice and found CD4 T cell dependence, with viral evasion limiting CD8 T cell function. MuHV-4 colonizes germinal center (GC) B cells via lytic transfer from myeloid cells, and CD4 T cells control myeloid infection. GC colonization and protective, lytic antigen-specific CD4 T cells are now evident also for EBV. Subunit vaccines have protected only transiently against MuHV-4, but whole virus vaccines give long-term protection, via CD4 T cells and antibody. They block infection transfer to B cells, and need include no known viral latency gene, nor any MuHV-4-specific gene. Thus, the Doherty approach of murine analysis has led to a plausible vaccine strategy for EBV and, perhaps, some insight into what CD8 T cells really do.