Sumoylation exerts minimal effects on the splicing regulatory activity of the influenza A virus non-structural protein NS1
One of the greatest challenges facing the development of a universal treatment for influenza infection is the virus's ability to mutate rapidly and produce new antigenic properties. Targeting the viral components of one strain does not ensure that the treatment will be effective with a newly developed strain. One alternative would be to develop therapies that target cellular factors the virus depends on for survivability. One of these factors is the cellular SUMOylation system. We have previously demonstrated that the Small Ubiquitin-like MOdifier (SUMO) interacts with the influenza virus by SUMOylating several viral proteins and by affecting the interferon blocking activity of its non-structural protein NS1. These interactions open the door to the potential development of a treatment that would not be constrained by virus specificity. Here, we further elucidate the ways in which the influenza virus is being affected by SUMOylation. Through confocal microscopy experiments where components of the cellular SUMOylation system were over-expressed through transfection, we were able to establish that with the over-expression of SUMO and the conjugating enzyme, Ubc9, cells were less likely to progress into the late stages of infection, characterized by the presence of the late viral M1 protein therefore suggesting a potential anti-influenza role for the cellular SUMOylation system. Furthermore, through RNP reconstitution assays and primer extension analyses, we discovered that the SUMOylation of NS1 plays a minor role in NS1's ability to regulate the splicing of viral gene transcripts. Taken together, these studies provide a deeper insight into the interplay between the influenza virus and the cellular SUMOylation system.
Melendez, Griselda, "Sumoylation exerts minimal effects on the splicing regulatory activity of the influenza A virus non-structural protein NS1" (2013). ETD Collection for University of Texas, El Paso. AAI1545183.