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

Resumo: Dengue 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.

Imprenta: Journal of Virology, v. 90, n. 1, p. 92-102, 2015

Identificador do objeto digital: 10.1128/JVI.01849-15

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya Virus - Virus ; Chikungunya virus - Dengue

Data de publicação: 2015