The University of Southampton
University of Southampton Institutional Repository

A conserved proline between domains II and III of hepatitis C virus NS5A influences both RNA replication and virus assembly

Hughes, Mair, Gretton, Sarah, Shelton, Holly, Brown, David D., McCormick, Christopher J., Angus, Allan G., Patel, Arvind H., Griffin, Stephen and Harris, Mark (2009) A conserved proline between domains II and III of hepatitis C virus NS5A influences both RNA replication and virus assembly Journal of Virology, 83, (20), pp. 10788-10796. (doi:10.1128/JVI.02406-08).

Record type: Article


We previously demonstrated that two closely spaced polyproline motifs, with the consensus sequence Pro-X-X-Pro-X-Lys/Arg, located between residues 343 to 356 of NS5A, mediated interactions with cellular SH3 domains. The N-terminal motif (termed PP2.1) is only conserved in genotype 1 isolates, whereas the C-terminal motif (PP2.2) is conserved throughout all hepatitis C virus (HCV) isolates, although this motif was shown to be dispensable for replication of the genotype 1b subgenomic replicon. In order to investigate the potential role of these motifs in the viral life cycle, we have undertaken a detailed mutagenic analysis of these proline residues in the context of both genotype 1b (FK5.1) or 2a subgenomic replicons and the genotype 2a infectious clone, JFH-1. We show that the PP2.2 motif is dispensable for RNA replication of all subgenomic replicons and, furthermore, is not required for virus production in JFH-1. In contrast, the PP2.1 motif is only required for genotype 1b RNA replication. Mutation of proline 346 within PP2.1 to alanine dramatically attenuated genotype 1b replicon replication in three distinct genetic backgrounds, but the corresponding proline 342 was not required for replication of the JFH-1 subgenomic replicon. However, the P342A mutation resulted in both a delay to virus release and a modest (up to 10-fold) reduction in virus production. These data point to critical roles for these proline residues at multiple stages in the HCV life cycle; however, they also caution against extrapolation of data from culture-adapted replicons to infectious virus

Full text not available from this repository.

More information

Published date: October 2009
Organisations: Infection Inflammation & Immunity


Local EPrints ID: 72618
ISSN: 0022-538X
PURE UUID: 89d37fb9-b91d-4ff7-8dd2-c902e44bb94a

Catalogue record

Date deposited: 18 Feb 2010
Last modified: 18 Jul 2017 23:53

Export record



Author: Mair Hughes
Author: Sarah Gretton
Author: Holly Shelton
Author: David D. Brown
Author: Allan G. Angus
Author: Arvind H. Patel
Author: Stephen Griffin
Author: Mark Harris

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.