A neonatal nonhuman primate model of gestational Zika virus infection with evidence of microencephaly, seizures and cardiomyopathy

Autoři: Rosemary J. Steinbach aff001;  Nicole N. Haese aff002;  Jessica L. Smith aff002;  Lois M. A. Colgin aff004;  Rhonda P. MacAllister aff005;  Justin M. Greene aff002;  Christopher J. Parkins aff002;  J. Beth Kempton aff006;  Edward Porsov aff006;  Xiaojie Wang aff007;  Lauren M. Renner aff008;  Trevor J. McGill aff008;  Brandy L. Dozier aff005;  Craig N. Kreklywich aff002;  Takeshi F. Andoh aff002;  Marjorie R. Grafe aff010;  Heidi L. Pecoraro aff011;  Travis Hodge aff012;  Robert M. Friedman aff008;  Lisa A. Houser aff013;  Terry K. Morgan aff010;  Peter Stenzel aff010;  Jonathan R. Lindner aff015;  Robert L. Schelonka aff016;  Jonah B. Sacha aff002;  Victoria H. J. Roberts aff001;  Martha Neuringer aff008;  John V. Brigande aff006;  Christopher D. Kroenke aff007;  Antonio E. Frias aff001;  Anne D. Lewis aff004;  Meredith A. Kelleher aff001;  Alec J. Hirsch aff002;  Daniel Neal Streblow aff002
Působiště autorů: Division of Reproductive & Developmental Sciences, Oregon National Primate Research Center, Beaverton, Oregon, United States of America aff001;  Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, Oregon, United States of America aff002;  Division of Pathobiology & Immunology, Oregon National Primate Research Center, Beaverton, Oregon, United States of America aff003;  Division of Comparative Medicine, Pathology Services Unit, Oregon National Primate Research Center, Beaverton, Oregon, United States of America aff004;  Division of Comparative Medicine, Clinical Medicine Unit, Oregon National Primate Research Center, Beaverton, Oregon, United States of America aff005;  Department of Otolaryngology, Oregon Hearing Research Center, Oregon Health & Science University, Portland, Oregon, United States of America aff006;  Advanced Imaging Research Center, Oregon Health & Science University, Portland, Oregon, United States of America aff007;  Department of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon, United States of America aff008;  Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States of America aff009;  Department of Pathology, Oregon Health & Science University, Portland, Oregon, United States of America aff010;  Veterinary Diagnostic Services Department, North Dakota State University, Fargo, North Dakota, United States of America aff011;  Division of Comparative Medicine, Time Mated Breeding Services Unit, Oregon National Primate Research Center, Beaverton, Oregon, United States of America aff012;  Division of Comparative Medicine, Behavioral Services Unit, Oregon National Primate Research Center, Beaverton, Oregon, United States of America aff013;  Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, United States of America aff014;  Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, United States of America aff015;  Division of Neonatology, Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America aff016
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227676


Zika virus infection during pregnancy is associated with miscarriage and with a broad spectrum of fetal and neonatal developmental abnormalities collectively known as congenital Zika syndrome (CZS). Symptomology of CZS includes malformations of the brain and skull, neurodevelopmental delay, seizures, joint contractures, hearing loss and visual impairment. Previous studies of Zika virus in pregnant rhesus macaques (Macaca mulatta) have described injury to the developing fetus and pregnancy loss, but neonatal outcomes following fetal Zika virus exposure have yet to be characterized in nonhuman primates. Herein we describe the presentation of rhesus macaque neonates with a spectrum of clinical outcomes, including one infant with CZS-like symptoms including cardiomyopathy, motor delay and seizure activity following maternal infection with Zika virus during the first trimester of pregnancy. Further characterization of this neonatal nonhuman primate model of gestational Zika virus infection will provide opportunities to evaluate the efficacy of pre- and postnatal therapeutics for gestational Zika virus infection and CZS.

Klíčová slova:

Euthanasia – Macaque – Neonates – Placenta – Pregnancy – Rhesus monkeys – Zika virus – Purkinje cells


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