RNA and Viruses: the machinery of pathogenesis

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.

Relevant Publications

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 (20C) : 76-81
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
RNA helicases and remodeling proteins
Anna Marie Pyle
Curr Opin Chem Biol. 2011 (15) : 636-642
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
The acidic domain of hepatitis C virus NS4A contributes to RNA replication and virus particle assembly
T. Phan, Andrew Kohlway, Peniel Dimberu, Anna Marie Pyle and Brett D. Lindenbach
J. Virol. 2011 (85) : 1193-1204
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