Participation of 3‐O‐sulfated heparan sulfates in the protection of macrophages by herpes simplex virus‐1 glycoprotein D and cyclophilin B against apoptosis
نویسندگان
چکیده
Heparan sulfates (HS) are involved in numerous biological processes, which rely on their ability to interact with a large panel of proteins. Although the reaction of 3-O-sulfation can be catalysed by the largest family of HS sulfotransferases, very few mechanisms have been associated with this modification and to date, only glycoprotein D (gD) of herpes simplex virus-1 (HSV-1 gD) and cyclophilin B (CyPB) have been well-described as ligands for 3-O-sulfated HS. Here, we hypothesized that both ligands could induce the same responses via a mechanism dependent on 3-O-sulfated HS. First, we checked that HSV-1 gD was as efficient as CyPB to induce the activation of the same signalling events in primary macrophages. We then demonstrated that both ligands efficiently reduced staurosporin-induced apoptosis and modulated the expression of apoptotic genes. In addition to 3-O-sulfated HS, HSV-1 gD was reported to interact with other receptors, including herpes virus entry mediator (HVEM), nectin-1 and -2. Thus, we decided to identify the contribution of each binding site in the responses triggered by HSV-1 gD and CyPB. We found that knock-down of 3-O-sulfotransferase 2, which is the main 3-O-sulfated HS-generating enzyme in macrophages, strongly reduced the responses induced by both ligands. Moreover, silencing the expression of HVEM rendered macrophages unresponsive to either HSV-1 gD and CyPB, thus indicating that both proteins induced the same responses by interacting with a complex formed by 3-O-sulfated HS and HVEM. Collectively, our results suggest that HSV-1 might hijack the binding sites for CyPB in order to protect macrophages against apoptosis for efficient infection.
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عنوان ژورنال:
دوره 7 شماره
صفحات -
تاریخ انتشار 2017