Viruses 2018, 10(10), 522; https://doi.org/10.3390/v10100522
Non-Uniform and Non-Random Binding of Nucleoprotein to Influenza A and B Viral RNA
Valerie Le Sage 1, Adalena V. Nanni 1, Amar R. Bhagwat 1, Dan J. Snyder 1,2, Vaughn S. Cooper 1,2, Seema S. Lakdawala 1,*
and Nara Lee 1,*
and Nara Lee 1,*
1
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15217, USA
2
Center for Evolutionary Biology and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15217, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Luis Martinez-Sobrido
Received: 15 August 2018 / Revised: 17 September 2018 / Accepted: 22 September 2018 / Published: 25 September 2018
(This article belongs to the Special Issue What’s New with Flu?)
Abstract
The genomes of influenza A and B viruses have eight, single-stranded RNA segments that exist in the form of a viral ribonucleoprotein complex in association with nucleoprotein (NP) and an RNA-dependent RNA polymerase complex. We previously used high-throughput RNA sequencing coupled with crosslinking immunoprecipitation (HITS-CLIP) to examine where NP binds to the viral RNA (vRNA) and demonstrated for two H1N1 strains that NP binds vRNA in a non-uniform, non-random manner. In this study, we expand on those initial observations and describe the NP-vRNA binding profile for a seasonal H3N2 and influenza B virus. We show that, similar to H1N1 strains, NP binds vRNA in a non-uniform and non-random manner. Each viral gene segment has a unique NP binding profile with areas that are enriched for NP association as well as free of NP-binding. Interestingly, NP-vRNA binding profiles have some conservation between influenza A viruses, H1N1 and H3N2, but no correlation was observed between influenza A and B viruses. Our study demonstrates the conserved nature of non-uniform NP binding within influenza viruses. Mapping of the NP-bound vRNA segments provides information on the flexible NP regions that may be involved in facilitating assembly. View Full-TextKeywords:
influenza virus; nucleoprotein; viral RNA; HITS-CLIP; viral ribonucleoprotein
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Le Sage, V.; Nanni, A.V.; Bhagwat, A.R.; Snyder, D.J.; Cooper, V.S.; Lakdawala, S.S.; Lee, N. Non-Uniform and Non-Random Binding of Nucleoprotein to Influenza A and B Viral RNA. Viruses 2018, 10, 522.
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