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J. Virol. doi:10.1128/JVI.02447-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

YELLOW FEVER VIRUS NS3 PLAYS AN ESSENTIAL ROLE IN VIRUS ASSEMBLY INDEPENDENT OF ITS KNOWN ENZYMATIC FUNCTIONS

Department of Biological Sciences, 915 W. State Street, Purdue University, West Lafayette, IN 47907-2054

^* To whom correspondence should be addressed. Email: kuhnr{at}purdue.edu.

	Abstract

In flaviviruses it has been proposed that there is a coupling between genome replication and virion assembly with the involvement of non-structural proteins in this process. It was previously reported that mutations in yellow fever virus (YFV) non-structural protein NS2A blocked production of infectious virus and this block could be released by a suppressor mutation in NS3. Here, based on studies using a YFV replicon-based trans-packaging system as well as full-length YFV cDNA, we report that mutation of a conserved tryptophan at position 349 in the helicase domain of NS3 blocks production of infectious virus particles, revealing an as yet unknown role for NS3 in virus assembly. Mutation of tryptophan 349 to alanine (W349A) had no effect on viral replication as demonstrated by wild type levels of viral RNA amplification and protein expression in W349A transfected cells. Although release of infectious virus was not detected, release of capsid-less subviral particles was not blocked. The assembly defect in W349A could be trans-complemented inefficiently using BHK-REP cells (a cell-line containing persistently replicating YFV replicon RNA). Trans-complementation was also demonstrated by supplying wild type NS2B-3 or NS3 protein alone as well as by supplying inactive NS2B-3 protein, indicating that this function of NS3 in virus assembly was independent of its known enzymatic functions.

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