Jayden Harris, Emory University

Jayden Harris (Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, USA), Jonathan Einterz Owen (Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, USA), Breanna N. Landry (Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada), Hannah C.H. Hauch (Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada), Christian M Beusch (Pathology Advanced Translational Research Unit (PATRU), Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA), David E Gordon (Pathology Advanced Translational Research Unit (PATRU), Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA), Selena M. Sagan (Department of Microbiology & Immunology, University of British Columbia, Vancouver, Canada), Christopher J. Neufeldt (Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA, USA; Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Division of Infectious Diseases, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA)

Expressing & Multiplying

Orthoflaviviruses (flaviviruses), including dengue virus and Zika virus (ZIKV), are a major global risk and there are few vaccines and no antivirals available for treatment. Viruses are obligate parasites that rely on cellular factors to support replication. A limited understanding of the flavivirus replication cycle and the host factors involved in virus replication creates challenges in searching for antiviral targets. Defining how host factors contribute to infection is critical for understanding flavivirus replication and identifying avenues for intervention. The flavivirus nonstructural (NS) protein, NS2A, has critical roles in viral genome replication and virion assembly, but how interactions between NS2A and host proteins specifically contribute to each process remain undefined. We have used pull-down mass spectrometry to identify host proteins that interact with ZIKV NS2A. Directed RNAi screening of NS2A-interacting proteins revealed several host factors that have significant functions in ZIKV replication or assembly. Of the identified factors, the host protein dymeclin (DYM) significantly decreased both viral infection and assembly of new viral particles, suggesting a critical role in early ZIKV infection. Based on these interactions between DYM and NS2A, we hypothesize that the flavivirus protein NS2A recruits DYM to facilitate virus replication, and that the requirement for DYM is conserved across the flavivirus family. By determining how DYM contributes to flavivirus infection, we will expand our knowledge about an understudied facet of flavivirus replication. We will also identify potentially conserved host-virus interactions across flaviviruses.