Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins

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Dengue virus (DENV) is a major arthropod-borne human pathogen, infecting more than 400 million individuals annually worldwide; however, neither a therapeutic drug nor a prophylactic vaccine is currently available. Amongst the DENV proteins, non-structural protein 1 (NS1) is one of the most enigmatic, being required for RNA replication, but also secreted from infected cells to counteract antiviral immune response, thus contributing to pathogenesis. Despite its essential role at early stages of the viral replication cycle, the molecular determinants governing NS1 functions are unknown. Here, we used a combination of genetic, high-resolution imaging and biochemical approaches and found that NS1 additionally plays an important role for the production of infectious virus particles. By using a novel trans-complementation system with fully functional epitope-tagged NS1, we show that NS1 interacts with the structural proteins residing in the envelope of the virus particle. An NS1 variant retained in the endoplasmic reticulum still supported efficient DENV particle production, demonstrating that secretion of NS1 is dispensable for virion production. This study expands the list of functions exerted by NS1 for the DENV replication cycle. Given this multi-functional nature, NS1 appears to be an attractive target for antiviral therapy.

Vyšlo v časopise: Dengue Virus Non-structural Protein 1 Modulates Infectious Particle Production via Interaction with the Structural Proteins. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005277
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005277

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