Bachelor of Science in Microbiology, University of Wisconsin – Madison
Christina is a third year PhD student in the tenOever Lab. Christina completed her B.S. degree in Microbiology at the University of Wisconsin – Madison where she studied the nuclear-cytoplasmic translocation of HIV-1 mRNA in the laboratory of Dr. Nathan Sherer. Between undergraduate and graduate school, she worked as an Associate Research Specialist in the laboratory of Dr. Andrew Mehle studying protein-protein interactions relevant to Influenza A virus. In the tenOever Lab, she studies kinase signaling pathways important for SARS-CoV-2 replication.
Nilsson-Payant BE, Uhl S, Grimont A, Doane AS, Cohen P, Patel RS, Higgins CA, Acklin JA, Bram Y, Chandar V, Blanco-Melo D, Panis M, Lim JK, Elemento O, Schwartz RE, Rosenberg BR, Chandwani R, tenOever BR
J Virol. 2021 Sep 15:JVI0125721 15/09/2021
Cells infected by influenza virus mount a large-scale antiviral response and most cells ultimately initiate cell-death pathways in an attempt to suppress viral replication. We performed a CRISPR-Cas9-knockout selection designed to identify host factors required for replication after viral entry. We identified a large class of presumptive antiviral factors that unexpectedly act as important proviral enhancers during influenza virus infection. One of these, IFIT2, is an interferon-stimulated gene with well-established antiviral activity but limited mechanistic understanding. As opposed to suppressing infection, we show in the present study that IFIT2 is instead repurposed by influenza virus to promote viral gene expression. CLIP-seq demonstrated that IFIT2 binds directly to viral and cellular messenger RNAs in AU-rich regions, with bound cellular transcripts enriched in interferon-stimulated mRNAs. Polysome and ribosome profiling revealed that IFIT2 prevents ribosome pausing on bound mRNAs. Together, the data link IFIT2 binding to enhanced translational efficiency for viral and cellular mRNAs and ultimately viral replication. Our findings establish a model for the normal function of IFIT2 as a protein that increases translation of cellular mRNAs to support antiviral responses and explain how influenza virus uses this same activity to redirect a classically antiviral protein into a proviral effector.
Nat Microbiol. 2020 Dec;5(12):1490-1503 24/08/2020
Larson GP, Tran V, Yú S, Caì Y, Higgins CA, Smith DM, Baker SF, Radoshitzky SR, Kuhn JH, Mehle A
Cell Rep. 2019 Nov 19;29(8):2175-2183.e4 19/11/2019
Ryan T Behrens, Mounavya Aligeti, Ginger M Pocock, Christina A Higgins, Nathan M Sherer
J Virol. 2017 Jan 18;91(3):e02107-16. 18/01/2017