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Journal of Virology, April 2007, p. 3731-3739, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02250-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sialic Acid on Herpes Simplex Virus Type 1 Envelope Glycoproteins Is Required for Efficient Infection of Cells{triangledown}

Jeremy R. Teuton1 and Curtis R. Brandt1,2,3*

Program in Cell and Molecular Biology,1 Department of Medical Microbiology and Immunology,2 Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin 537063

Received 13 October 2006/ Accepted 8 January 2007

Herpes simplex virus type 1 (HSV-1) envelope proteins are posttranslationally modified by the addition of sialic acids to the termini of the glycan side chains. Although gC, gD, and gH are sialylated, it is not known whether sialic acids on these envelope proteins are functionally important. Digestion of sucrose gradient purified virions for 4 h with neuraminidases that remove both {alpha}2,3 and {alpha}2,6 linked sialic acids reduced titers by 1,000-fold. Digestion with a {alpha}2,3-specific neuraminidase had no effect, suggesting that {alpha}2,6-linked sialic acids are required for infection. Lectins specific for either {alpha}2,3 or {alpha}2,6 linkages blocked attachment and infection to the same extent. In addition, the mobility of gH, gB, and gD in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels was altered by digestion with either {alpha}2,3 specific neuraminidase or nonspecific neuraminidases, indicating the presence of both linkages on these proteins. The infectivity of a gC-1-null virus, {Delta}gC2-3, was reduced to the same extent as wild-type virus after neuraminidase digestion, and attachment was not altered. Neuraminidase digestion of virions resulted in reduced VP16 translocation to the nucleus, suggesting that the block occurred between attachment and entry. These results show for the first time that sialic acids on HSV-1 virions play an important role in infection and suggest that targeting virion sialic acids may be a valid antiviral drug development strategy.


* Corresponding author. Mailing address: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, 6630 Medical Sciences Center, 1300 University Avenue, Madison, WI 53706. Phone: (608) 262-8054. Fax: (608) 262-0479. E-mail: crbrandt{at}wisc.edu

{triangledown} Published ahead of print on 17 January 2007.


Journal of Virology, April 2007, p. 3731-3739, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02250-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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