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Deepak Shukla, Ghadah Karasneh, Sarolta Bacsa, Tibor Valyi-Nagy; Up-regulation Of Syndecan Expression May Be A Viral-induced Mechanism For HSV-1 Shedding. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5866.
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To evaluate novel molecular mechanism(s) that may promote HSV-1 detachment and shedding from cells.
Wild-type HSV-1(KOS) was examined for ability to alter the expression of syndecan-1, a heparan sulfate (HS) proteoglycan to which the HSV-1 binds during attachment to cells. RNA interference was used for down-regulating syndecan-1 expression. Virus shedding was determined by plaque assays upon treatment with syndecan shedding agonist (phorbol ester PMA) or antagonist (tyrphostin A25). Protein expression in corneal epithelial and other cell-types was examined by flow cytometry and Western blot analysis. Antibody treatments were used for probing the activity of syndecan-1 in HSV-1 infection cycle. A time course assay was performed to determine syndecan-1 and heparan sulfate expression upon HSV-1 (KOS) infection.
HSV-1 infection is accompanied by a constant increase in syndecan-1 expression. However, the increase in syndecan expression, which is an attachment co-receptor for HSV-1, does not result in an increased ability of the virus to infect cells. In contrast, the infectivity of HSV-1 goes down with the passage of time. Our data suggests that ongoing HSV-1 infection results in an increase in syndecan-1 shedding rate, which is likely meant to facilitate virus detachment or shedding from cell surfaces. To support this result, a syndecan shedding agonist enhanced virus release (shedding) by more than 30%. Overall, the virus yield was significantly enhanced by the syndecan shedding agonist (PMA) treatment.
HSV-1 is able to enhance syndecan-1 expression upon infection. However, the enhanced syndecan-1 expression fails to correlate with enhanced infectivity. In contrast, it correlates well with enhanced syndecan-1 shedding and stronger HSV-1 release from the infected cells. We propose that the increase in syndecan-1 expression is a novel, previously unreported, molecular mechanism by which HSV-1 facilitates its detachment and hence, shedding from the cells of the cornea.
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