Autor(es)Carnec Xavier, Meertens Laurent, Dejarnac Ophélie, Perera-Lecoin Manuel, Hafirassou Mohamed Lamine, Kitaura Jiro, Ramdasi Rasika, Schwartz Olivier, Amara Ali

ResumoDengue virus (DENV) is the etiological agent of the major human arboviral disease. We previously demonstrated that the TIM - TAM families of phosphatidylserine (PtdSer) receptors involved in the phagocytosis of apoptotic cells mediate DENV entry into target cells. We show here that human CD300a, a recently identified phospholipid receptor, also binds directly DENV particles - enhances viral entry. CD300a facilitates infection of the four DENV serotypes, as well as of other mosquito-borne viruses such as West Nile virus - Chikungunya virus. CD300a acts as an attachment factor that enhances DENV internalization through clathrin-mediated endocytosis. CD300a recognizes predominantly phosphatidylethanolamine (PtdEth) - to a lesser extent PtdSer associated with viral particles. Mutation of residues in the IgV domain critical for phospholipid binding abrogate CD300a-mediated enhancement of DENV infection. Finally, we show that CD300a is expressed at the surface of primary macrophages - anti-CD300a polyclonal antibodies partially inhibited DENV infection of these cells. Overall, these data indicate that CD300a is a novel DENV binding receptor that recognizes PtdEth - PtdSer present on virions - enhance infection. Dengue disease, caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease of humans - is a major global health concern. The molecular bases of DENV-host cell interactions during virus entry are poorly understood, hampering the discovery of new targets for antiviral intervention. We recently discovered that the TIM - TAM proteins, two receptor families involved in the phosphatidylserine (PtdSer)-dependent phagocytic removal of apoptotic cells, interact with DENV particles-associated PtdSer through a mechanism that mimics the recognition of apoptotic cells - mediate DENV infection. In this study, we show that CD300a, a novel identified phospholipid receptor, mediates DENV infection. CD300a-dependent DENV infection relies on the direct recognition of phosphatidylethanolamine - to a lesser extent PtdSer associated with viral particles. This study provides novel insights into the mechanisms that mediate DENV entry - reinforce the concept that DENV uses an apoptotic mimicry strategy for viral entry.

ImprentaJournal of Virology, v. 90, n. 1, p. 92-102, 2015

DescritoresChikungunya virus - Cell ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya Virus - Virus ; Chikungunya virus - Dengue

Data de Publicação:2015