ANNOUNCEMENTS
Dengue is a global public health concern with over 390 million cases reported annually. Dengue NS5 protein being the RNA-dependent RNA polymerase of the virus is crucial for viral replication. Various lines of evidence indicate that DENV-NS5 can interact with several host proteins to influence other aspects of host cell physiology as well. In this work, two parallel approaches have been utilized for identification of human proteins interacting with DENV-NS5. One is a computational approach wherein protein sequence as well as structure-based information are used to predict the human proteins that could possibly interact with DENV-NS5 protein. The second approach is experimental, involving co-immunoprecipitation of NS5 protein from a dengue-infected monocytic cell line (U937-DC-SIGN) using rabbit anti-DENV-NS5 antibodies followed by identification of interacting proteins using mass spectrometry. Both bioinformatic and experimental approaches have led to the identification of some known as well as several novel protein interactors of DENV-NS5 participating in various cellular pathways such as ubiquitin mediated proteolysis, cellular metabolism, cell cycle, autophagy, mRNA processing, immune response etc., strongly suggesting that the function of NS5 during dengue infection likely extends well beyond its known functions as a viral replicase and RNA capping enzyme, and could inform therapeutic strategies focused on overcoming the adverse effects of dengue infection on the immune response.
