title: Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues.
abstract: Zika virus (ZIKV), an emerging flavivirus, has recently spread explosively through the Western hemisphere. In addition to symptoms including fever, rash, arthralgia, and conjunctivitis, ZIKV infection of pregnant women can cause microcephaly and other developmental abnormalities in the fetus. We report herein the results of ZIKV infection of adult rhesus macaques. Following subcutaneous infection, animals developed transient plasma viremia and viruria from 1-7 days post infection (dpi) that was accompanied by the development of a rash, fever and conjunctivitis. Animals produced a robust adaptive immune response to ZIKV, although systemic cytokine response was minimal. At 7 dpi, virus was detected in peripheral nervous tissue, multiple lymphoid tissues, joints, and the uterus of the necropsied animals. Notably, viral RNA persisted in neuronal, lymphoid and joint/muscle tissues and the male and female reproductive tissues through 28 to 35 dpi. The tropism and persistence of ZIKV in the peripheral nerves and reproductive tract may provide a mechanism of subsequent neuropathogenesis and sexual transmission.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Alec J
authors.initials: AJ
authors.lastname: Hirsch
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Smith
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Nicole N
authors.identifier: 0000-0003-4871-2763
authors.initials: NN
authors.lastname: Haese
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Rebecca M
authors.identifier: 0000-0003-3740-5442
authors.initials: RM
authors.lastname: Broeckel
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Parkins
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Kreklywich
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Victor R
authors.initials: VR
authors.lastname: DeFilippis
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Denton
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Smith
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, United States of America.
authors.forename: William B
authors.initials: WB
authors.lastname: Messer
authors.affiliation: Pathology Services Unit, Division of Comparative Medicine, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Lois M A
authors.initials: LM
authors.lastname: Colgin
authors.affiliation: Pathology Services Unit, Division of Comparative Medicine, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Ducore
authors.affiliation: Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Peta L
authors.initials: PL
authors.lastname: Grigsby
authors.affiliation: Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.|Department of Obstetrics & Gynecology, Oregon Health and Science University, Portland, Oregon, United States of America.
authors.forename: Jon D
authors.initials: JD
authors.lastname: Hennebold
authors.affiliation: Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Tonya
authors.initials: T
authors.lastname: Swanson
authors.affiliation: Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Alfred W
authors.initials: AW
authors.lastname: Legasse
authors.affiliation: Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.affiliation: Clinical Medicine Unit, Division of Comparative Medicine, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Rhonda
authors.initials: R
authors.lastname: MacAllister
authors.affiliation: UPMC Presbyterian Hospital, Division of Neuropathology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Clayton A
authors.identifier: 0000-0002-2697-7691
authors.initials: CA
authors.lastname: Wiley
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.|Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.|Division of Pathobiology and Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Streblow
mesh_terms: D000818:Animals; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D017403:In Situ Hybridization; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D014766:Viremia / Q000821:virology; D000071244:Zika Virus; D000071243:Zika Virus Infection / Q000473:pathology* / Q000821:virology*