Effect of DNA Repair Protein Rad18 on Viral Infection

Abstract

Host factors belonging to the DNA repair machineries are assumed to aid retroviruses in the obligatory step of integration. Here we describe the effect of DNA repair molecule Rad18, a component of the post-replication repair pathway, on viral infection. Contrary to our expectations, cells lacking Rad18 were consistently more permissive to viral transduction as compared to Rad18^+/+ controls. Remarkably, such susceptibility was integration independent, since retroviruses devoid of integration activity also showed enhancement of the initial steps of infection. Moreover, the elevated sensitivity of the Rad18^−/− cells was also observed with adenovirus. These data indicate that Rad18 suppresses viral infection in a non-specific fashion, probably by targeting incoming DNA. Furthermore, considering data published recently, it appears that the interactions between DNA repair components with incoming viruses, often result in inhibition of the infection rather than cooperation toward its establishment. Various cellular factors are thought to interact with invading retroviruses, either assisting the viral proteins or functioning as protecting factors against them. Productive viral infection, therefore, depends on the way the equilibrium between these two opposite group of molecules is leaning. The authors find that Rad18, a component of the post-replication DNA repair pathway, instead of aiding retroviral infection suppresses its establishment, interfering with the accumulation of the invading DNA. They also find that such suppressive activity is not restricted only to retroviruses but also concerns adenovirus infection. These results, in conjunction with those recently published, lead the authors to hypothesize a role for DNA repair mediated genome stability maintenance in viral infection, or in other words, that viral invasion is also a matter of genome stability.