NS1; Ribosomal stalk; PA-X; Influenza A Virus; influenza a virus, NS1, PA-X, ribosomal stalk
Abstract :
[en] Influenza A NS1 and PA-X proteins play a major role in the virus replication cycle by interfering innate immune system in the infected cells. Host translation machinery is required for viral protein translation and consequently replication. We identified several binary interactions between NS1, PA-X and host cell factors involved in translation regulation using GPCA method. Few interactions were further confirmed by co-immunoprecipitation. We demonstrated whether these NS1/PA-X interactors are essential cellular factors that support influenza A virus replication. Among these NS1/PA-X interactors, we identified that RPLP0 knockdown drastically decreased virus titers upon virus infection. Since RPLP0 interacts with RPLP1/2 heterodimers to form the ribosomal stalk, we also conducted the same demonstration upon RPLP2 knockdown in which the reduction of virus titers was observed. Finally, we further provided the evidence that RPLP0, RPLP2 knockdown drastically impaired ion channel M2 protein accumulation implying the role of these ribosomal stalk proteins in viral protein translation. This approach may lead to the development of antiviral drugs against influenza viruses (Flu) by specifically targeting the interplay between NS1/PA-X and the ribosomal stalk.