Prospects of a novel vaccination strategy for human gamma-herpesviruses

Abstract

Due to the oncogenic potential associated with persistent infection of human gamma-herpesviruses, including Epstein-Barr virus (EBV or HHV-4) and Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8), vaccine development has focused on subunit vaccines. However, the results using an animal model of mouse infection with a related rodent virus, murine gamma-herpesvirus 68 (MHV-68, γHV-68, or MuHV-4), have shown that the only effective vaccination strategy is based on live attenuated viruses, including viruses engineered to be incapable of establishing persistence. Vaccination with a virus lacking persistence would eliminate many potential complications. Progress in understanding persistent infections of EBV and KSHV raises the possibility of engineering a live attenuated virus without persistence. Therefore, we should keep the option open for developing a live EBV or KSHV vaccine.

Figure 1

A rationale design of live vaccines for EBV and KSHV. A simplified representation for the genome organizations of MHV-68, KSHV, and EBV modified from Virgin et al. [19] is presented. The gray boxes indicate conserved gene blocks among three viruses. The latent genes are labeled green and the viral immediate early transcriptional factors are labeled red. The genes proposed to be deleted are indicated by a thin crossed line. The striped boxes at the end of viral genomes correspond to terminal repeats. In the EBV genome, there is the other striped box that represents the large internal repeat region which encodes latent genes, such as EBNA2 and EBNA5.