Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques.

Szczegóły
Abstrakt

Tytuł:: Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques.
Autorzy:: Mavigner M; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Raper J; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Kovacs-Balint Z; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Gumber S; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
O'Neal JT; Emory Vaccine Center, Atlanta, GA 30329, USA.
Bhaumik SK; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Zhang X; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Habib J; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Mattingly C; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
McDonald CE; Emory Vaccine Center, Atlanta, GA 30329, USA.
Avanzato V; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Burke MW; Department of Physiology and Biophysics, Howard University, Washington, DC 20060, USA.
Magnani DM; Department of Pathology, University of Miami, Miami, FL 33146, USA.
Bailey VK; Department of Pathology, University of Miami, Miami, FL 33146, USA.
Watkins DI; Department of Pathology, University of Miami, Miami, FL 33146, USA.
Vanderford TH; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Fair D; Oregon Health and Science University, Portland, OR 97239, USA.
Earl E; Oregon Health and Science University, Portland, OR 97239, USA.
Feczko E; Oregon Health and Science University, Portland, OR 97239, USA.
Styner M; Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599, USA.
Jean SM; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Cohen JK; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Silvestri G; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Johnson RP; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
O'Connor DH; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA.
Wrammert J; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Suthar MS; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.; Emory Vaccine Center, Atlanta, GA 30329, USA.
Sanchez MM; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Alvarado MC; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Chahroudi A; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA. .; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.; Children's Healthcare of Atlanta, Atlanta, GA 30322, USA.
Źródło:: Science translational medicine [Sci Transl Med] 2018 Apr 04; Vol. 10 (435).
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Washington, DC : American Association for the Advancement of Science
MeSH Terms:: Brain/*pathology
Brain/*virology
Zika Virus Infection/*complications
Zika Virus Infection/*pathology
Animals ; Animals, Newborn ; Brain/diagnostic imaging ; Brain/physiopathology ; Female ; Macaca mulatta ; Magnetic Resonance Imaging ; Male ; Pregnancy ; RNA, Viral/genetics ; Zika Virus Infection/diagnostic imaging ; Zika Virus Infection/physiopathology
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Grant Information:: T32 GM008169 United States GM NIGMS NIH HHS; P51 OD011132 United States OD NIH HHS; P51 OD011107 United States OD NIH HHS; R01 DE022287 United States DE NIDCR NIH HHS; T15 LM007088 United States LM NLM NIH HHS; R01 DE019064 United States DE NIDCR NIH HHS
Substance Nomenclature:: 0 (RNA, Viral)
Entry Date(s):: Date Created: 20180406 Date Completed: 20190923 Latest Revision: 20190923
Update Code:: 20240104
PubMed Central ID:: PMC6186170
DOI:: 10.1126/scitranslmed.aao6975
PMID:: 29618564
: Czasopismo naukowe

The Zika virus (ZIKV) epidemic is associated with fetal brain lesions and other serious birth defects classified as congenital ZIKV syndrome. Postnatal ZIKV infection in infants and children has been reported; however, data on brain anatomy, function, and behavioral outcomes following infection are absent. We show that postnatal ZIKV infection of infant rhesus macaques (RMs) results in persistent structural and functional alterations of the central nervous system compared to age-matched controls. We demonstrate ZIKV lymphoid tropism and neurotropism in infant RMs and histopathologic abnormalities in the peripheral and central nervous systems including inflammatory infiltrates, astrogliosis, and Wallerian degeneration. Structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) show persistent enlargement of lateral ventricles, maturational changes in specific brain regions, and altered functional connectivity (FC) between brain areas involved in emotional behavior and arousal functions, including weakened amygdala-hippocampal connectivity in two of two ZIKV-infected infant RMs several months after clearance of ZIKV RNA from peripheral blood. ZIKV infection also results in distinct alterations in the species-typical emotional reactivity to acute stress, which were predicted by the weak amygdala-hippocampal FC. We demonstrate that postnatal ZIKV infection of infants in this model affects neurodevelopment, suggesting that long-term clinical monitoring of pediatric cases is warranted.
(Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

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