Structured RNA molecules and helicase enzymes are essential for viral function, especially in the case of Hepatitis C virus (HCV) and flaviviruses (such as Dengue or Yellow Fever), which are major threats to world health. Our goal is to solve the molecular structure of the HCV and flaviviral replicase machines, and to deduce their roles in pathogenicity. In this way, we hope to develop new, broad-spectrum therapeutics against existing and emerging viruses. We recently determined the molecular mechanism of RNA unwinding by the NS3 helicase from HCV using a combination of enzymology and crystallography. Having established this foundation, we have are now developing approaches for visualizing intact replicases and monitoring their dynamical function in living cells.
RNA and Viruses: the machinery of pathogenesis
Relevant Publications
A rapid RIG-I signaling relay mediates efficient antiviral response Daniel T Thoresen, Drew Galls, Benjamin Götte, Wenshuai Wang, Anna M Pyle Mol Cell 2022 () : in press |
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The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands Wenshuai Wang, Anna Marie Pyle Mol Cell 2022 (82) : 4131-4144.e6 |
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Evolving a RIG-I antagonist: a modified DNA aptamer mimics viral RNA Xiaoming Ren, Amy D. Gelinas, Melissa Linehan, Akiko Iwasaki, Wenshuai Wang, Nebojsa Janjic, Anna Marie Pyle Journal of Molecular Biology 2021 (433) : 167227 |
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NS3 from HCV strain JFH-1 is an unusually robust helicase that is primed to bind and unwind viral RNA Ting Zhou, Xiaoming Ren, Rebecca L. Adams and Anna Marie Pyle J Virol. 2018 (92) : e01253-17 |
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Functional RNA structures throughout the Hepatitis C Virus genome Rebecca L. Adams, Nathan Pirakitikulr and Anna Marie Pyle Curr Opin Virol. 2017 (24) : 79-86 |
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Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells Ellen F. Foxman, James A. Storer, Megan E. Fitzgerald, Bethany R. Wasik, Lin Hou, Hongyu Zhao, Paul E. Turner, Anna Marie Pyle and Akiko Iwasaki Proc. Natl. Acad. Sci. USA 2015 (112) : 827-832 |
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The linker region of NS3 plays a critical role in the replication and infectivity of hepatitis C virus Andrew Kohlway, Nathan Pirakitikulr, Steve C. Ding, Feng Yang, Dahai Luo, Brett D. Lindenbach and Anna Marie Pyle J Virol. 2014 (18) : 10970-10974 |
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An evolving arsenal: viral RNA detection by RIG-I-like receptors Megan Fitzgerald, David C. Rawling, Adriana Vela and Anna Marie Pyle Curr Opin Microbiol. 2014 (20) : 76-81 |
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Hepatitis C virus RNA replication and virus particle assembly require specific dimerization of the NS4A protein transmembrane domain Andrew Kohlway, Nathan Pirakitikulr, Francisco N. Barrera, Olga Potapova, Donald M. Engelman, Anna Marie Pyle and Brett D. Lindenbach J Virol. 2014 (88) : 628-42 |
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RNA helicases and remodeling proteins Anna Marie Pyle Curr Opin Chem Biol. 2011 (15) : 636-642 |
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Unmasking the active helicase conformation of NS3 from Hepatitis C virus Steve C. Ding, Andrew S. Kohlway and Anna Marie Pyle J Virol. 2011 (85) : 4343-4353 |
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The acidic domain of hepatitis C virus NS4A contributes to RNA replication and virus particle assembly Tung Phan, Andrew Kohlway, Peniel Dimberu, Anna Marie Pyle and Brett D. Lindenbach J Virol. 2011 (85) : 1193-1204 |
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The NS4A protein from hepatitis C virus promotes RNA-coupled ATP hydrolysis by the NS3 helicase Rudolf K. Beran, Brett D. Lindenbach. and Anna M. Pyle J Virol. 2009 (83) : 3268-3275 |