Differences in the susceptibility of herpes simplex virus types 1 and 2 to modified heparin compounds suggest serotype differences in viral entry

Betsy Herold, Susan I. Gerber, Brian J. Belval, Alicia M. Siston, Nancy Shulman

Research output: Contribution to journalArticle

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Abstract

Although heparan sulfate (HS) serves as an initial receptor for the binding of both herpes simplex virus type 1 (HSV-1) and HSV-2 to cell surfaces, the two serotypes differ in epidemiology, cell tropism, and ability to compete for viral receptors in vitro. These observations are not necessarily contradictory and can be explained if the two serotypes recognize different structural features of HS. To compare the specific features of NS important for the binding and infection of HSV-1 and HSV-2, we took advantage of structural similarities between heparin and cell surface HS and compared the abilities of chemically modified heparin compounds to inhibit plaque formation. We found that the antiviral activity of heparin for both serotypes was independent of anticoagulant activity. Moreover, specific negatively charged regions of the polysaccharide, including N sulfations and the carboxyl groups, are key structural features for interactions of both HSV-1 and HSV-2 with cell surfaces since N desulfation or carboxyl reduction abolished heparin's antiviral activity. In contrast, 6-O sulfations and 2- ,3-O sulfations are important determinants primarily for HSV-1 infection. The O-desulfated heparins had little or no inhibitory effect on HSV-1 infection but inhibited HSV-2 infection. Using a series of intertypic recombinant mutant viruses, we found that susceptibility to O-desulfated heparins can be transferred to HSV-1 by the gene for glycoprotein C of HSV-2 (gC-2). This supports the notion that the envelope glycoproteins of HSV-1 and HSV-2 interact with different affinities for different structural features of heparin. To determine if the modified heparin compounds inhibited plaque formation by competing with cell surface HS for viral attachment, binding studies were also performed. As anticipated, most compounds inhibited binding and plaque formation in parallel. However, several compounds inhibited the binding of HSV-1 to cells during the initial attachment period at 4°C; this inhibitory effect was reversed when the cells and inoculum were shifted to 37°C. This temperature-dependent differential response to modified heparin compounds was evident primarily when glycoprotein C of HSV-1 (gC-1) was present in the virion envelope. Minimal temperature-dependent differences were seen for HSV-1 with gC-1 deleted and for HSV-2. These results suggest differences in the interactions of HSV-1 and HSV-2 with cell surface HS that may influence cell tropism.

Original languageEnglish (US)
Pages (from-to)3461-3469
Number of pages9
JournalJournal of Virology
Volume70
Issue number6
StatePublished - 1996
Externally publishedYes

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Human herpesvirus 2
Human herpesvirus 1
Human Herpesvirus 2
Human Herpesvirus 1
heparin
Heparin
serotypes
Heparitin Sulfate
cells
glycoproteins
tropisms
Tropism
Virus Diseases
infection
Antiviral Agents
Serogroup
anticoagulant activity
receptors
Temperature
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Differences in the susceptibility of herpes simplex virus types 1 and 2 to modified heparin compounds suggest serotype differences in viral entry. / Herold, Betsy; Gerber, Susan I.; Belval, Brian J.; Siston, Alicia M.; Shulman, Nancy.

In: Journal of Virology, Vol. 70, No. 6, 1996, p. 3461-3469.

Research output: Contribution to journalArticle

Herold, Betsy ; Gerber, Susan I. ; Belval, Brian J. ; Siston, Alicia M. ; Shulman, Nancy. / Differences in the susceptibility of herpes simplex virus types 1 and 2 to modified heparin compounds suggest serotype differences in viral entry. In: Journal of Virology. 1996 ; Vol. 70, No. 6. pp. 3461-3469.
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AU - Gerber, Susan I.

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AU - Shulman, Nancy

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