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Domain III of NS5A contributes to both RNA replication and assembly of hepatitis C virus particles

University of Leeds

¹ E-mail: m.harris{at}leeds.ac.uk

The hepatitis C virus (HCV) NS5A protein plays a critical role in viral RNA replication, and has recently been shown to play a role in particle production in the infectious genotype 2a HCV clone (JFH-1). Here we show that alanine substitution of serines 2428/2430 within the C-terminal domain III of NS5A do not affect subgenomic replicon RNA replication but reduce particle production. In contrast substitution of serines 2390/2391 had no effect on either RNA replication or particle production. Relative to genotype 1, all genotype 2 HCV isolates contain a 19 residue insertion near the C-terminus of domain III which, when deleted (2408-2426), resulted in a delay to both RNA replication and particle production. None of these mutations affected the ratio of basal to hyperphosphorylated NS5A, suggesting that serines between residues 2390-2430 are not phosphorylated. We propose that although domain III is dispensable for RNA replication, it nevertheless influences this process.

Received 2 December 2008; accepted 24 February 2009.

This article has been cited by other articles:

				M. Hughes, S. Gretton, H. Shelton, D. D. Brown, C. J. McCormick, A. G. N. Angus, A. H. Patel, S. Griffin, and M. Harris A Conserved Proline between Domains II and III of Hepatitis C Virus NS5A Influences both RNA Replication and Virus Assembly J. Virol., October 15, 2009; 83(20): 10788 - 10796. [Abstract] [Full Text] [PDF]