The role of chikungunya virus nsP1 protein in virus replication.

Lead Research Organisation: University of Leeds
Department Name: Sch of Molecular & Cellular Biology

Abstract

BACKGROUND:
Chikungunya virus (CHIKV) is a positive single-stranded RNA virus transmitted between mosquitos to humans. It re-emerged as an epidemic in 2005 around the Indian Ocean, before spreading across Asia, Africa, Europe and North/South America. CHIKV establishes persistent infection with chronic, debilitating musculoskeletal pain and neurological complications. There is no vaccine or antiviral therapy, with development hampered by lack of insight into its biology.
OBJECTIVES AND EXPERIMENTAL APPROACH:
Using cutting-edge molecular virology, biochemical and structural techniques, this project will investigate the function and molecular structure of CHIKV non-structural protein-1 (nsP1). NsP1 is responsible for non-conventional cytoplasmic capping of CHIKV genomes, via a novel multi-step methyltransferase/guanyltransferase process.

NOVELTY:
CHIKV replication and in particular the function and molecular structure of nsP1 is poorly understood. The preliminary results discussed above are novel and unpublished.
TIMELINES:
With no vaccine or antiviral therapy, CHIKV is major public health issue and economic burden. It has reached epidemic levels in various areas and continues to spread across the USA and Europe. Consequently, there is pressing need to understand how the virus controls replication and identify antiviral targets.
The proposed project fits clearly within the BBSRC theme of mechanistic biology and world-class fundamental bioscience. We will investigate mechanisms by which CHIKV interacts with fundamental process of host cell capping, investigating differences between human and mosquito cell environments and co-factors. We anticipate that results will provide a greater understanding of how such mechanisms are organized, function and interact across a range of related viruses. Importantly, we expected
that analysis of such mechanisms using a virus model will inform our understanding of non-canonical capping mechanisms within less tractable mammalian and mosquito eukaryotic cell systems.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011151/1 30/09/2015 29/09/2023
2110916 Studentship BB/M011151/1 30/09/2018 31/12/2022 Kate Loveday