Abstract
Promyelocytic leukemia protein (PML) is an essential organizer of PML nuclear bodies (NBs), which carry out a variety of activities, including antiviral functions. Herpesviruses from all subfamilies encode proteins that counteract PML NB-mediated antiviral defenses by multiple mechanisms. However, because of the species specificity of herpesviruses, only a limited number of in vivo studies have been undertaken to investigate the effect of PML or PML NBs on herpesvirus infection. To address this central issue in herpesvirus biology, we studied the course of infection in wild-type and PML⁻/⁻ mice using murine gammaherpesvirus 68 (MHV68), which encodes a tegument protein that induces PML degradation. While acute infection in PML⁻/⁻ mice progressed similarly to that in wild-type mice, the lytic reactivation frequency was higher in peritoneal exudate cells, due to both an increase of MHV68 genome-positive cells and greater reactivation efficiency. We also detected a higher frequency of persistent infection in PML⁻/⁻ peritoneal cells. These findings suggest that the PML protein can repress the establishment or maintenance of gammaherpesvirus latency in vivo. Further use of the PML⁻/⁻ mouse model should aid in dissecting the molecular mechanisms that underlie the role of PML in gammaherpesvirus latency and may yield clues for how PML modulates herpesvirus latency in general.