Abstract:
The human -herpesviruses, EBV and Kaposi’s sarcoma-associated herpesvirus, are widely disseminated and are associated with
the onset of a variety of malignancies. Thus, the development of prophylactic and therapeutic vaccination strategies is an important
goal. The experimental mouse -herpesvirus, HV68 (or MHV-68), has provided an in vivo model for studying immune
control of these persistent viruses. In the current studies, we have examined infectivity, immunogenicity, and protective efficacy
following infection with a replication-deficient HV68 blocked in late viral gene expression, ORF31STOP. The data show that
ORF31STOP was able to latently infect B cells. However, the anatomical site and persistence of the infection depended on the route
of inoculation, implicating a role for viral replication in viral spread but not the infectivity per se. Furthermore, i.p. infection with
ORF31STOP elicited strong cellular immunity but a non-neutralizing Ab response. In contrast, intranasal infection was poorly
immunogenic. Consistent with this, mice infected i.p. had enhanced control of both the lytic and latent viral loads following
challenge with wild-type HV68, whereas intranasal infected mice were not protected. These data provide important insight into
mechanisms of infection and protective immunity for the -herpesviruses and demonstrate the utility of replication-deficient
mutant viruses in direct testing of “proof of principal” vaccination strategies.
