Herpes simplex virus (HSV) fusion with cells requires the gD, gB, and gH/gL glycoprotein quartet. gD serves as a receptor binding glycoprotein. gB and gH/gL execute fusion in an as-yet-unclear manner. To better understand the role of gH/gL in HSV entry, we produced a soluble version of gH/gL carrying a One-STrEP tag (gH(t.st)/gL). Previous findings implicated integrins as possible ligands to gH/gL (C. Parry et al., J. Gen. Virol. 86:7-10, 2005). We report that (i) gH(t.st)/gL bound a number of cells in a dose-dependent manner at concentrations similar to those required for the binding of soluble gB or gD. (ii) gH(t.st)/gL inhibited HSV entry at the same concentrations required for binding. It also inhibited cell-cell fusion in transfected cells. (iii) The absence of beta3 integrin did not prevent the binding of gH(t.st)/gL to CHO cells and infection inhibition. Conversely, integrin-negative K562 cells did not acquire the ability to bind gH(t.st)/gL when hyperexpressing alphaVbeta3 integrin. (iv) Constitutive expression of wild-type gH/gL (wt-gH/gL) restricted infection in all of the cell lines tested, a behavior typical of glycoproteins which bind cellular receptors. The extent of restriction broadly paralleled the efficiency of gH/gL transfection. RGD motif mutant gH/gL could not be differentiated from wt-gH with respect to restriction of infection. Cumulatively, the present results provide several lines of evidence that HSV gH/gL interacts with a cell surface cognate protein(s), that this protein is not necessarily an alphaVbeta3 integrin, and that this interaction is required for the process of virus entry/fusion.

Herpes simplex virus glycoproteins H/L bind to cells independently of alpha V- beta 3 integrin and inhibit virus entry, and their constitutive expression restricts infection / Gianni T.; Cerretani A.; Dubois R.; Salvioli S.; Blystone S.S.; Rey F.; Campadelli-Fiume G.. - In: JOURNAL OF VIROLOGY. - ISSN 0022-538X. - STAMPA. - 84:(2010), pp. 4013-4025. [10.1128/JVI.02502-09]

Herpes simplex virus glycoproteins H/L bind to cells independently of alpha V- beta 3 integrin and inhibit virus entry, and their constitutive expression restricts infection.

GIANNI, TATIANA;SALVIOLI, STEFANO;CAMPADELLI, MARIA GABRIELLA
2010

Abstract

Herpes simplex virus (HSV) fusion with cells requires the gD, gB, and gH/gL glycoprotein quartet. gD serves as a receptor binding glycoprotein. gB and gH/gL execute fusion in an as-yet-unclear manner. To better understand the role of gH/gL in HSV entry, we produced a soluble version of gH/gL carrying a One-STrEP tag (gH(t.st)/gL). Previous findings implicated integrins as possible ligands to gH/gL (C. Parry et al., J. Gen. Virol. 86:7-10, 2005). We report that (i) gH(t.st)/gL bound a number of cells in a dose-dependent manner at concentrations similar to those required for the binding of soluble gB or gD. (ii) gH(t.st)/gL inhibited HSV entry at the same concentrations required for binding. It also inhibited cell-cell fusion in transfected cells. (iii) The absence of beta3 integrin did not prevent the binding of gH(t.st)/gL to CHO cells and infection inhibition. Conversely, integrin-negative K562 cells did not acquire the ability to bind gH(t.st)/gL when hyperexpressing alphaVbeta3 integrin. (iv) Constitutive expression of wild-type gH/gL (wt-gH/gL) restricted infection in all of the cell lines tested, a behavior typical of glycoproteins which bind cellular receptors. The extent of restriction broadly paralleled the efficiency of gH/gL transfection. RGD motif mutant gH/gL could not be differentiated from wt-gH with respect to restriction of infection. Cumulatively, the present results provide several lines of evidence that HSV gH/gL interacts with a cell surface cognate protein(s), that this protein is not necessarily an alphaVbeta3 integrin, and that this interaction is required for the process of virus entry/fusion.
2010
Herpes simplex virus glycoproteins H/L bind to cells independently of alpha V- beta 3 integrin and inhibit virus entry, and their constitutive expression restricts infection / Gianni T.; Cerretani A.; Dubois R.; Salvioli S.; Blystone S.S.; Rey F.; Campadelli-Fiume G.. - In: JOURNAL OF VIROLOGY. - ISSN 0022-538X. - STAMPA. - 84:(2010), pp. 4013-4025. [10.1128/JVI.02502-09]
Gianni T.; Cerretani A.; Dubois R.; Salvioli S.; Blystone S.S.; Rey F.; Campadelli-Fiume G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/89704
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