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Document Type:Latin Dissertation
Language of Document:English
Record Number:54006
Doc. No:TL23960
Call number:‭NR41279‬
Main Entry:Charlene Ranadheera
Title & Author:Functional characterization of the Nipah virus nucleocapsid protein and its implications on Nipah virus replicationCharlene Ranadheera
College:University of Manitoba (Canada)
Date:2008
Degree:Ph.D.
student score:2008
Page No:246
Abstract:Nipah virus (NiV) was identified as the causative agent for outbreaks of meningitis, encephalitis, and respiratory disease in Malaysia, Singapore, Bangladesh, and India. Due to the ease in transmission, high fatality rates and lack of preventative or therapeutic treatments NiV has been classified as a biosafety level 4 agent. This emphasizes the need for research focusing on the development of effective vaccines and/or antiviral therapies against NiV infections. The objective of this study was to determine whether interfering with normal interactions between the NiV nucleocapsid protein (N) and the NiV phosphoprotein (P) would result in the disruption of viral replication. Together with NiV P and the NiV polymerase protein (L), NiV N forms a replicase that generates full-length anti-genomic and genomic RNA. The newly synthesized full-length genomic viral RNA is encapsidated by NiV N as a fundamental step in virus particle formation. For both of these processes to occur, it is essential that NiV N interacts with NiV P. In the absence of NiV N, NiV P along with NiV L forms a transcriptase, which is responsible for the synthesis of viral mRNA. I hypothesized that transient recombinant expression of NiV N would interact with virally-expressed NiV P, causing a functional transformation of the transcriptase into a replicase. This hypothetical change in function, the transcriptase to a replicase, would lead to the impairment of viral transcription and translation, thereby causing an overall disruption to viral replication. The work presented here demonstrates that increased expression of recombinant NiV N correlated with a 74% and 98% decrease in viral transcription and translation, respectively, and a 94% decrease in the production of full-length genomic RNA. As a result, infectivity levels decreased by 4 orders of magnitude in cells expressing recombinant NiV N when compared to those of control cells. Similar results were obtained when using truncated NiV N peptides containing the binding domains for NiV P. These findings provide a novel target for the development of antivirals aimed at disrupting the viral polymerase complex of negative-stranded viruses.
Subject:Biological sciences; Nipah virus; Nucleocapsid protein; Viral replication; Virology; 0720:Virology
Added Entry:University of Manitoba (Canada)