Receptors and routes of dengue virus entry into the host cells.
Dengue 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.
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Christine
C
Cruz-Oliveira
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal.
João Miguel
JM
Freire
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Thaís M
TM
Conceição
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
Luiza M
LM
Higa
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal.
Miguel A R B
MA
Castanho
Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil dapoian@bioqmed.ufrj.br.
Andrea T
AT
Da Poian
D000818:Animals; D003715:Dengue / Q000473:pathology; D003716:Dengue Virus / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D053586:Virus Internalization
D011991:Receptors, Virus
flavivirus; genome translocation; internalization routes; membrane fusion; viral structural proteins; virus recognition