Dr. Eric Bortz, Cell Molecular Biologist position finalist to give lecture on Jan. 25

Wednesday, Jan. 25, 4-5 p.m.
Administration Building, Room 204

The Department of Biological Sciences and INBRE are pleased to have Dr. Eric Bortz, finalist for the Cell Molecular Biologist position, present "A Host Cell Protein Network Regulating Highly Pathogenic Avian Influenza Virus Replication."

Dr. Bortz is a research assistant professor in the Department of Microbiology at the Mount Sinai School of Medicine, New York.

Abstract:
Influenza A viruses (Orthomyxoviridae) cause seasonal epidemics in humans, and lethal global pandemics including 1918 (H1N1), 1957 (H2N2), 1968 (H3N2), and 2009 (swine-origin H1N1). Highly pathogenic avian influenza A (HPAI) strains of the H5N1 subtype emerged in southeast China in 1997, and subsequently spread in wild and domestic birds to other parts of Asia, Europe and Africa. H5N1 HPAI viruses are capable of crossing the species barrier into humans, causing a significant pulmonary disease characterized by uncontrolled inflammatory responses (hypercytokinemia, or "cytokine storm") and severe pneumonia. Adaptation of the viral RNA-dependent RNA polymerase to interactions with mammalian host proteins contributes to the efficiency of viral RNA synthesis (viral gene expression and genome replication), and to disease severity in humans. To uncover mechanisms by which human host factors might regulate HPAI replication, the molecular requirements for a network of proteins on both H1N1 and H5N1 HPAI virus replication were mapped by functional genomics using in silico biological network analysis and RNA interference (RNAi) experiments. Of 31 human proteins studied that interact with the influenza virus heterotrimeric polymerase (PB1, PB2, and PA) and nucleoprotein (NP), 18 (58%) were required for both H1N1 and H5N1 polymerase function. Conversely, host proteins that antagonize H5N1 HPAI polymerase potentially affect synthesis of viral RNA pathogen-associated molecular patterns (PAMPs) that stimulate innate immune pathways leading to induction of interferon β (IFNβ), and contributing to hypercytokinemia. Remarkably, RNA-binding proteins such as DEAD-box RNA helicase 17 (DDX17) also governed the H5N1 HPAI polymerase's adaptability to human cells. Thus, this network of virus-host interactions may control adaptation, replication and pathogenicity of HPAI viruses in humans, and provide promising therapeutic targets for antiviral drugs.