title: Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection.
abstract: Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus-Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE.
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.
authors.forename: Nunya
authors.initials: N
authors.lastname: Chotiwan
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA.
authors.forename: John T
authors.initials: JT
authors.lastname: Roehrig
authors.affiliation: Department of Medicine, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Schlesinger
authors.affiliation: Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Carol D
authors.initials: CD
authors.lastname: Blair
authors.affiliation: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA. Electronic address: yxh0@cdc.gov.
authors.forename: Claire Y-H
authors.initials: CY
authors.lastname: Huang
mesh_terms: D019067:Antibody-Dependent Enhancement; D002460:Cell Line; D003716:Dengue Virus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D017452:Receptors, IgG / Q000378:metabolism*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D014759:Viral Envelope Proteins
keywords: Antibody-dependent enhancement; Dengue virus; Envelope protein; FcγRIIA; Virus entry