Evasion of oncogene-induced senescence by gammaherpesviruses

A common feature of herpesvirus infection is activation of DNA damage responses (DDRs) that are essential for efficient lytic replication. Latent infection with Epstein–Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) also elicit DDRs via the action of latent viral oncoproteins that deregulate cell proliferation and initiate a host anti-proliferative defense known as oncogene-induced senescence (OIS). These viruses encode auxiliary latent proteins that undermine OIS to allow the ongoing proliferation of infected cells despite robust DDR signaling. Persistent DDRs have also been linked to the aberrant secretion of pathogenetically important inflammatory mediators from infected cells. The accumulating evidence indicates that herpesviruses have evolved ways to co-opt DDR signaling to manage both latent and lytic phases of infection, and that DDR subversion may contribute to herpesvirus-associated disease states.

► Herpesviruses induce DNA damage responses (DDRs) that facilitate lytic replication.
► Oncogenic stress caused by latent infection with EBV or KSHV also activates DDRs.
► DDR signaling can trigger cellular senescence, permanently arresting the cell cycle.
► Auxiliary viral gene products allow ongoing proliferation of latently infected cells.
► Viral usurpation of DDR signaling and autophagy remodels secretory pathways.