title: Enhancement of Zika virus pathogenesis by preexisting antiflavivirus immunity.
abstract: Zika virus (ZIKV) is spreading rapidly into regions around the world where other flaviviruses, such as dengue virus (DENV) and West Nile virus (WNV), are endemic. Antibody-dependent enhancement has been implicated in more severe forms of flavivirus disease, but whether this also applies to ZIKV infection is unclear. Using convalescent plasma from DENV- and WNV-infected individuals, we found substantial enhancement of ZIKV infection in vitro that was mediated through immunoglobulin G engagement of Fcγ receptors. Administration of DENV- or WNV-convalescent plasma into ZIKV-susceptible mice resulted in increased morbidity-including fever, viremia, and viral loads in spinal cord and testes-and increased mortality. Antibody-dependent enhancement may explain the severe disease manifestations associated with recent ZIKV outbreaks and highlights the need to exert great caution when designing flavivirus vaccines.
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Susana V
authors.identifier: 0000-0002-6776-2697
authors.initials: SV
authors.lastname: Bardina
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Paul
authors.identifier: 0000-0001-8408-4640
authors.initials: P
authors.lastname: Bunduc
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Shashank
authors.identifier: 0000-0002-1254-9979
authors.initials: S
authors.lastname: Tripathi
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: James
authors.identifier: 0000-0003-2077-6685
authors.initials: J
authors.lastname: Duehr
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Justin J
authors.identifier: 0000-0002-7514-8873
authors.initials: JJ
authors.lastname: Frere
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Brown
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Raffael
authors.identifier: 0000-0001-5568-5420
authors.initials: R
authors.lastname: Nachbagauer
authors.affiliation: American Red Cross, Gaithersburg, MD 20877, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Foster
authors.affiliation: American Red Cross, Gaithersburg, MD 20877, USA.
authors.forename: David
authors.identifier: 0000-0003-4926-4675
authors.initials: D
authors.lastname: Krysztof
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Domenico
authors.identifier: 0000-0003-0961-3535
authors.initials: D
authors.lastname: Tortorella
authors.affiliation: American Red Cross, Gaithersburg, MD 20877, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Stramer
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. adolfo.garcia-sastre@mssm.edu florian.krammer@mssm.edu jean.lim@mssm.edu.|Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.|Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Adolfo
authors.identifier: 0000-0002-6551-1827
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. adolfo.garcia-sastre@mssm.edu florian.krammer@mssm.edu jean.lim@mssm.edu.
authors.forename: Florian
authors.identifier: 0000-0003-4121-776X
authors.initials: F
authors.lastname: Krammer
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. adolfo.garcia-sastre@mssm.edu florian.krammer@mssm.edu jean.lim@mssm.edu.
authors.forename: Jean K
authors.identifier: 0000-0002-4572-6417
authors.initials: JK
authors.lastname: Lim
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D019067:Antibody-Dependent Enhancement / Q000276:immunology*; D003289:Convalescence; D003715:Dengue / Q000097:blood / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D010949:Plasma / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D050795:STAT2 Transcription Factor / Q000235:genetics; D019562:Viral Load; D014901:West Nile Fever / Q000097:blood / Q000276:immunology*; D014902:West Nile virus / Q000276:immunology; D000071244:Zika Virus / Q000276:immunology*; D000071243:Zika Virus Infection / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D011961:Receptors, Fc; D050795:STAT2 Transcription Factor; C494085:Stat2 protein, mouse