title: Antibody Responses to Zika Virus Infections in Environments of Flavivirus Endemicity.
abstract: Zika virus (ZIKV) infections occur in areas where dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and other viruses of the genusFlaviviruscocirculate. The envelope (E) proteins of these closely related flaviviruses induce specific long-term immunity, yet subsequent infections are associated with cross-reactive antibody responses that may enhance disease susceptibility and severity. To gain a better understanding of ZIKV infections against a background of similar viral diseases, we examined serological immune responses to ZIKV, WNV, DENV, and YFV infections of humans and nonhuman primates (NHPs). Using printed microarrays, we detected very specific antibody responses to primary infections with probes of recombinant E proteins from 15 species and lineages of flaviviruses pathogenic to humans, while high cross-reactivity between ZIKV and DENV was observed with 11 printed native viruses. Notably, antibodies from human primary ZIKV or secondary DENV infections that occurred in areas where flavivirus is endemic broadly recognized E proteins from many flaviviruses, especially DENV, indicating a strong influence of infection history on immune responses. A predictive algorithm was used to tentatively identify previous encounters with specific flaviviruses based on serum antibody interactions with the multispecies panel of E proteins. These results illustrate the potential impact of exposure to related viruses on the outcome of ZIKV infection and offer considerations for development of vaccines and diagnostics.
authors.affiliation: Department of Biology, University of Maryland-Baltimore County, Baltimore, Maryland, USA.|Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Keasey
authors.affiliation: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Pugh
authors.affiliation: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Stig M R
authors.initials: SMR
authors.lastname: Jensen
authors.affiliation: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Smith
authors.affiliation: Naval Medical Research Center, Silver Spring, Maryland, USA, and U.S. Naval Medical Research Unit No. 6 (NAMRU-6), Lima, Peru.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Hontz
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Dudley
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.affiliation: Molecular and Translational Sciences Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA robert.g.ulrich.civ@mail.mil.|Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D000917:Antibody Formation; D003429:Cross Reactions; D019353:Endemic Diseases; D018178:Flaviviridae Infections / Q000276:immunology* / Q000662:veterinary*; D006801:Humans; D008253:Macaca mulatta; D046228:Microarray Analysis; D018419:Primate Diseases / Q000276:immunology; D040081:Protein Array Analysis
chemical_list: D000914:Antibodies, Viral
keywords: Zika; cross-reactivity; flavivirus; humoral immunity; protein microarray