Receptors and routes of dengue virus entry into the host cells

© FEMS 2014. All rights reservedDengue is the most prevalent arthropod-borne viral disease, caused by dengue virus, a member of the Flaviviridae family. Its worldwide incidence is now a major health problem, with 2.5 billion people living in risk areas. In this review, we integrate the structural rearrangements of each viral protein and their functions in all the steps of virus entry into the host cells. We describe in detail the putative receptors and attachment factors in mammalian and mosquito cells, and the recognition of viral immunocomplexes via Fcγ receptor in immune cells. We also discuss that virus internalization might occur through distinct entry pathways, including clathrin-mediated or non-classical clathrin-independent endocytosis, depending on the host cell and virus serotype or strain. The implications of viral maturation in virus entry are also explored. Finally, we discuss the mechanisms of viral genome access to the cytoplasm. This includes the role of low pH-induced conformational changes in the envelope protein that mediate membrane fusion, and original insights raised by our recent work that supports the hypothesis that capsid protein would also be an active player in this process, acting on viral genome translocation into the cytoplasm.This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil, Projects 471239/2012-7 and 306669/2013-7), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, Brazil, Projects E-26/102.919/2011 and E-26/111.668/2013), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil, Project 171/2012), Fundação para a Ciência e Tecnologia – Ministério da Educação e Ciência (FCT-MEC, Portugal, Project PTDC/QUI-BIQ/112929/2009)