PMID- 37873381
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240210
DP  - 2023 Oct 14
TI  - Disruption of myelin structure and oligodendrocyte maturation in a pigtail 
      macaque model of congenital Zika infection.
LID - 2023.10.11.561759 [pii]
LID - 10.1101/2023.10.11.561759 [doi]
AB  - Zika virus (ZikV) infection during pregnancy can cause congenital Zika syndrome 
      (CZS) and neurodevelopmental delay in non-microcephalic infants, of which the 
      pathogenesis remains poorly understood. We utilized an established pigtail 
      macaque maternal-to-fetal ZikV infection/exposure model to study fetal brain 
      pathophysiology of CZS manifesting from ZikV exposure in utero. We found prenatal 
      ZikV exposure led to profound disruption of fetal myelin, with extensive 
      downregulation in gene expression for key components of oligodendrocyte 
      maturation and myelin production. Immunohistochemical analyses revealed marked 
      decreases in myelin basic protein intensity and myelinated fiber density in 
      ZikV-exposed animals. At the ultrastructural level, the myelin sheath in 
      ZikV-exposed animals showed multi-focal decompaction consistent with perturbation 
      or remodeling of previously formed myelin, occurring concomitant with 
      dysregulation of oligodendrocyte gene expression and maturation. These findings 
      define fetal neuropathological profiles of ZikV-linked brain injury underlying 
      CZS resulting from ZikV exposure in utero. Because myelin is critical for 
      cortical development, ZikV-related perturbations in oligodendrocyte function may 
      have long-term consequences on childhood neurodevelopment, even in the absence of 
      overt microcephaly.
FAU - Tisoncik-Go, Jennifer
AU  - Tisoncik-Go J
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Stokes, Caleb
AU  - Stokes C
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
AD  - Department of Pediatrics, University of Washington, Seattle, Washington, USA.
FAU - Whitmore, Leanne S
AU  - Whitmore LS
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Newhouse, Daniel J
AU  - Newhouse DJ
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Voss, Kathleen
AU  - Voss K
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Gustin, Andrew
AU  - Gustin A
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Sung, Cheng-Jung
AU  - Sung CJ
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Smith, Elise
AU  - Smith E
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Stencel-Baerenwald, Jennifer
AU  - Stencel-Baerenwald J
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
FAU - Parker, Edward
AU  - Parker E
AD  - Department of Ophthalmology, NEI Core for Vision Research, University of 
      Washington, Seattle, Washington, USA.
FAU - Snyder, Jessica M
AU  - Snyder JM
AD  - Department of Comparative Medicine, University of Washington, Seattle, 
      Washington, USA.
FAU - Shaw, Dennis W
AU  - Shaw DW
AD  - Department of Radiology, University of Washington, Seattle Washington, USA.
FAU - Rajagopal, Lakshmi
AU  - Rajagopal L
AD  - Department of Pediatrics, University of Washington, Seattle, Washington, USA.
AD  - Center for Global Infectious Disease Research, Seattle Children's Research 
      Institute, Seattle, Washington, USA.
AD  - Department of Global Health, University of Washington, Seattle, Washington, USA.
FAU - Kapur, Raj P
AU  - Kapur RP
AD  - Department of Pathology, University of Washington, Seattle, Washington, USA.
AD  - Department of Pathology, Seattle Children's Hospital, Seattle, Washington, USA.
FAU - Waldorf, Kristina Adams
AU  - Waldorf KA
AD  - Department of Global Health, University of Washington, Seattle, Washington, USA.
AD  - Department of Obstetrics & Gynecology, University of Washington, Seattle, 
      Washington, USA.
AD  - Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
FAU - Gale, Michael Jr
AU  - Gale M Jr
AD  - Center for Innate Immunity and Immune Disease, Department of Immunology, 
      University of Washington, Seattle, Washington, USA.
AD  - Department of Global Health, University of Washington, Seattle, Washington, USA.
AD  - Department of Obstetrics & Gynecology, University of Washington, Seattle, 
      Washington, USA.
LA  - eng
GR  - HHSN272201800008I/AI/NIAID NIH HHS/United States
GR  - P51 OD010425/OD/NIH HHS/United States
GR  - P30 EY001730/EY/NEI NIH HHS/United States
GR  - K08 AI150996/AI/NIAID NIH HHS/United States
GR  - HHSN272201800008C/AI/NIAID NIH HHS/United States
GR  - R01 AI145296/AI/NIAID NIH HHS/United States
GR  - R01 AI143265/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20231014
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
PMC - PMC10592731
EDAT- 2023/10/24 06:41
MHDA- 2023/10/24 06:42
PMCR- 2023/10/23
CRDT- 2023/10/24 03:56
PHST- 2023/10/24 06:41 [pubmed]
PHST- 2023/10/24 06:42 [medline]
PHST- 2023/10/24 03:56 [entrez]
PHST- 2023/10/23 00:00 [pmc-release]
AID - 2023.10.11.561759 [pii]
AID - 10.1101/2023.10.11.561759 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Oct 14:2023.10.11.561759. doi: 
      10.1101/2023.10.11.561759.