RT info:eu-repo/semantics/article
T1 The Tight Junction-Associated Protein Occludin Is Required for a Postbinding Step in Hepatitis C Virus Entry and Infection.
A1 Valenzuela Fernández, Agustín
A1 Benedicto, Ignacio
A1 Molina Jiménez, Francisca
A1 Bartosch, Birke
A1 Cosset, Franc¸ois-Loïc
A1 Lavillette, Dimitri
A1 Prieto, Jesús
A1 Moreno Otero, Ricardo
A1 Aldabe, Rafael
A1 López Cabrera, Manuel
A1 Majano, Pedro L.
A2 Medicina Física y Farmacología
A2 Grupo "Inmunología Celular y Viral".
AB The precise mechanisms regulating hepatitis C virus (HCV) entry into hepatic cells remain unknown.However, several cell surface proteins have been identified as entry factors for this virus. Of these molecules,claudin-1, a tight junction (TJ) component, is considered a coreceptor required for HCV entry. Recently, wehave demonstrated that HCV envelope glycoproteins (HCVgp) promote structural and functional TJ alterations. Additionally, we have shown that the intracellular interaction between viral E2 glycoprotein andoccludin, another TJ-associated protein, could be the cause of the mislocalization of TJ proteins. Herein wedemonstrated, by using cell culture-derived HCV particles (HCVcc), that interference of occludin expressionmarkedly reduced HCV infection. Furthermore, our results with HCV pseudotyped particles indicated thatoccludin, but not other TJ-associated proteins, such as junctional adhesion molecule A or zonula occludensprotein 1, was required for HCV entry. Using HCVcc, we demonstrated that occludin did not play an essentialrole in the initial attachment of HCV to target cells. Surface protein labeling experiments showed that bothexpression levels and cell surface localization of HCV (co)receptors CD81, scavenger receptor class B type I,and claudin-1 were not affected upon occludin knockdown. In addition, immunofluorescence confocal analysisshowed that occludin interference did not affect subcellular distribution of the HCV (co)receptors analyzed.However, HCVgp fusion-associated events were altered after occludin silencing. In summary, we propose thatoccludin plays an essential role in HCV infection and probably affects late entry events. This observation mayprovide new insights into HCV infection and related pathogenesis.
YR 2009
FD 2009
LK http://riull.ull.es/xmlui/handle/915/35316
UL http://riull.ull.es/xmlui/handle/915/35316
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DS Repositorio institucional de la Universidad de La Laguna
RD 14-oct-2024