Mutational analysis of Rift Valley fever phlebovirus nucleocapsid protein indicates novel conserved, functional amino acids

Mottram, T. J., Li, P. , Dietrich, I., Shi, X. , Brennan, B. , Varjak, M. and Kohl, A. (2017) Mutational analysis of Rift Valley fever phlebovirus nucleocapsid protein indicates novel conserved, functional amino acids. PLoS Neglected Tropical Diseases, 11(12), e0006155. (doi:10.1371/journal.pntd.0006155) (PMID:29267287) (PMCID:PMC5764413)

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Abstract

Rift Valley fever phlebovirus (RVFV; Phenuiviridae, Phlebovirus) is an important mosquito-borne pathogen of both humans and ruminants. The RVFV genome is composed of tripartite, single stranded, negative or ambisense RNAs. The small (S) segment encodes both the nucleocapsid protein (N) and the non-structural protein (NSs). The N protein is responsible for the formation of the viral ribonucleoprotein (RNP) complexes, which are essential in the virus life cycle and for the transcription and replication of the viral genome. There is currently limited knowledge surrounding the roles of the RVFV nucleocapsid protein in viral infection other than its key functions: N protein multimerisation, encapsidation of the RNA genome and interactions with the RNA-dependent RNA polymerase, L. By bioinformatic comparison of the N sequences of fourteen phleboviruses, mutational analysis, minigenome assays and packaging assays, we have further characterised the RVFV N protein. Amino acids P11 and F149 in RVFV N play an essential role in the function of RNPs and are neither associated with N protein multimerisation nor known nucleocapsid protein functions and may have additional roles in the virus life cycle. Amino acid Y30 exhibited increased minigenome activity despite reduced RNA binding capacity. Additionally, we have determined that the N-terminal arm of N protein is not involved in N-L interactions. Elucidating the fundamental processes that involve the nucleocapsid protein will add to our understanding of this important viral protein and may influence future studies in the development of novel antiviral strategies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mottram, Mr Timothy and Dietrich, Dr Isabelle and Li, Dr Ping and Varjak, Dr Margus and Brennan, Dr Benjamin and Shi, Dr Xiaohong and Kohl, Professor Alain
Authors: Mottram, T. J., Li, P., Dietrich, I., Shi, X., Brennan, B., Varjak, M., and Kohl, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Published Online:21 December 2017
Copyright Holders:Copyright © 2017 Mottram et al.
First Published:First published in PLoS Neglected Tropical Diseases 11(12):e0006155
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn McLauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH
5887510BBSRC Doctoral Training Partnership 2012George BaillieBiotechnology and Biological Sciences Research Council (BBSRC)BB/J013854/1MVLS COLLEGE SENIOR MANAGEMENT