J Gen Virol Faster Access
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Published online ahead of print on 29 April 2009 as doi:10.1099/vir.0.011221-0
Journal of General Virology 2009;90:1937.

A more recent version of this article appeared on August 1, 2009 J Gen Virol (2009), DOI 10.1099/vir.0.011221-0
© 2009 Society for General Microbiology
This Article
Right arrow Full Text (Papers in Press[PDF])
Right arrow All Versions of this Article:
vir.0.011221-0v1
90/8/1937    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Biswas, S.
Right arrow Articles by Field, H. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Biswas, S.
Right arrow Articles by Field, H. J.
Agricola
Right arrow Articles by Biswas, S.
Right arrow Articles by Field, H. J.

A mutation in helicase motif IV of HSV-1 UL5 that results in reduced growth in vitro and lower virulence in a murine infection model is related to predicted helicase structure

Subhajit Biswas1,3, Ricardo Núñez Miguel1, Soumi Sukla1 and Hugh J. Field2

1 University of Cambridge;
2 Cambridge University

3 E-mail: sb507{at}cam.ac.uk

A variant was selected from a clinical isolate of HSV-1 during a single passage in the presence of a helicase-primase inhibitor (HPI) at 8 times the IC50 concentration. The variant was approx. 40-fold resistant and showed significantly reduced growth in tissue culture with a concomitant reduction in virulence in a murine infection model. The variant contained a single mutation (Asn342Lys) in the UL5 predicted functional helicase motif IV. The Asn342Lys mutation was transferred to a laboratory strain, PDK cl-1 and the recombinant acquired the expected resistance and reduced growth characteristics. Comparative modelling and docking studies predicted the Asn342 position to be physically distant from the HPI-interaction pocket formed by UL5 and UL52 (primase). We suggest this mutation results in steric/allosteric modification of the HPI-binding pocket, conferring an indirect resistance to the HPI. Slower growth and moderately reduced virulence suggest that this mutation might also interfere with the helicase-primase activity.

Received 20 February 2009; accepted 24 April 2009.




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
INT J SYST EVOL MICROBIOL MICROBIOLOGY J GEN VIROL
J MED MICROBIOL ALL SGM JOURNALS
Copyright © 2009 by the Society for General Microbiology.