PMID- 35926066
OWN - NLM
STAT- MEDLINE
DCOM- 20220818
LR  - 20230217
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 16
IP  - 8
DP  - 2022 Aug
TI  - Fetal loss in pregnant rhesus macaques infected with high-dose African-lineage 
      Zika virus.
PG  - e0010623
LID - 10.1371/journal.pntd.0010623 [doi]
LID - e0010623
AB  - Countermeasures against Zika virus (ZIKV), including vaccines, are frequently 
      tested in nonhuman primates (NHP). Macaque models are important for understanding 
      how ZIKV infections impact human pregnancy due to similarities in placental 
      development. The lack of consistent adverse pregnancy outcomes in ZIKV-affected 
      pregnancies poses a challenge in macaque studies where group sizes are often 
      small (4-8 animals). Studies in small animal models suggest that African-lineage 
      Zika viruses can cause more frequent and severe fetal outcomes. No adverse 
      outcomes were observed in macaques exposed to 1x104 PFU (low dose) of 
      African-lineage ZIKV at gestational day (GD) 45. Here, we exposed eight pregnant 
      rhesus macaques to 1x108 PFU (high dose) of African-lineage ZIKV at GD 45 to test 
      the hypothesis that adverse pregnancy outcomes are dose-dependent. Three of eight 
      pregnancies ended prematurely with fetal death. ZIKV was detected in both fetal 
      and placental tissues from all cases of early fetal loss. Further refinements of 
      this exposure system (e.g., varying the dose and timing of infection) could lead 
      to an even more consistent, unambiguous fetal loss phenotype for assessing ZIKV 
      countermeasures in pregnancy. These data demonstrate that high-dose exposure to 
      African-lineage ZIKV causes pregnancy loss in macaques and also suggest that 
      ZIKV-induced first trimester pregnancy loss could be strain-specific.
FAU - Raasch, Lauren E
AU  - Raasch LE
AUID- ORCID: 0000-0003-0280-3678
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Yamamoto, Keisuke
AU  - Yamamoto K
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Newman, Christina M
AU  - Newman CM
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Rosinski, Jenna R
AU  - Rosinski JR
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Shepherd, Phoenix M
AU  - Shepherd PM
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Razo, Elaina
AU  - Razo E
AD  - Department of Pediatrics, UW Madison, Madison, Wisconsin, United States of 
      America.
FAU - Crooks, Chelsea M
AU  - Crooks CM
AD  - Department of Pathobiological Sciences, UW Madison, Madison, Wisconsin, United 
      States of America.
FAU - Bliss, Mason I
AU  - Bliss MI
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Breitbach, Meghan E
AU  - Breitbach ME
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Sneed, Emily L
AU  - Sneed EL
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Weiler, Andrea M
AU  - Weiler AM
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Zeng, Xiankun
AU  - Zeng X
AD  - United States Army Medical Research Institute of Infectious Diseases, Fort 
      Detrick, Maryland, United States of America.
FAU - Noguchi, Kevin K
AU  - Noguchi KK
AD  - Department of Psychiatry, Washington University School of Medicine, Saint Louis, 
      Missouri, United States of America.
FAU - Morgan, Terry K
AU  - Morgan TK
AD  - Department of Pathology, Oregon Health and Science University, Portland, Oregon, 
      United States of America.
AD  - Department of Obstetrics and Gynecology, Oregon Health and Science University, 
      Portland, Oregon, United States of America.
FAU - Fuhler, Nicole A
AU  - Fuhler NA
AD  - Department of Psychiatry, Washington University School of Medicine, Saint Louis, 
      Missouri, United States of America.
FAU - Bohm, Ellie K
AU  - Bohm EK
AD  - Department of Veterinary and Biomedical Sciences, University of Minnesota, 
      Minneapolis, Minnesota, United States of America.
FAU - Alberts, Alexandra J
AU  - Alberts AJ
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Havlicek, Samantha J
AU  - Havlicek SJ
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Kabakov, Sabrina
AU  - Kabakov S
AD  - Department of Kinesiology Occupational Therapy Program, University of Wisconsin 
      Madison, Madison, Wisconsin, United States of America.
FAU - Mitzey, Ann M
AU  - Mitzey AM
AD  - Department of Comparative Biosciences, UW Madison, Madison, Wisconsin, United 
      States of America.
FAU - Antony, Kathleen M
AU  - Antony KM
AD  - Department of Obstetrics and Gynecology, UW Madison, Madison, Wisconsin, United 
      States of America.
FAU - Ausderau, Karla K
AU  - Ausderau KK
AD  - Department of Kinesiology Occupational Therapy Program, University of Wisconsin 
      Madison, Madison, Wisconsin, United States of America.
AD  - Waisman Center, UW Madison, Madison, Wisconsin, United States of America.
FAU - Mejia, Andres
AU  - Mejia A
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Basu, Puja
AU  - Basu P
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Simmons, Heather A
AU  - Simmons HA
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Eickhoff, Jens C
AU  - Eickhoff JC
AD  - Department of Biostatistics and Medical Informatics, UW Madison, Madison, 
      Wisconsin, United States of America.
FAU - Aliota, Matthew T
AU  - Aliota MT
AD  - Department of Veterinary and Biomedical Sciences, University of Minnesota, 
      Minneapolis, Minnesota, United States of America.
FAU - Mohr, Emma L
AU  - Mohr EL
AD  - Department of Pediatrics, UW Madison, Madison, Wisconsin, United States of 
      America.
FAU - Friedrich, Thomas C
AU  - Friedrich TC
AD  - Department of Pathobiological Sciences, UW Madison, Madison, Wisconsin, United 
      States of America.
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Golos, Thaddeus G
AU  - Golos TG
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
AD  - Department of Veterinary and Biomedical Sciences, University of Minnesota, 
      Minneapolis, Minnesota, United States of America.
AD  - Department of Kinesiology Occupational Therapy Program, University of Wisconsin 
      Madison, Madison, Wisconsin, United States of America.
FAU - O'Connor, David H
AU  - O'Connor DH
AUID- ORCID: 0000-0003-2139-470X
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
AD  - Wisconsin National Primate Research Center, UW Madison, Madison, Wisconsin, 
      United States of America.
FAU - Dudley, Dawn M
AU  - Dudley DM
AD  - Department of Pathology and Laboratory Medicine, UW Madison, Madison, Wisconsin, 
      United States of America.
LA  - eng
GR  - R01 AI132563/AI/NIAID NIH HHS/United States
GR  - P01 AI132132/AI/NIAID NIH HHS/United States
GR  - P51 OD011106/OD/NIH HHS/United States
GR  - P50 HD103525/HD/NICHD NIH HHS/United States
GR  - K08 AI139341/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220804
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Female
MH  - Humans
MH  - Macaca mulatta
MH  - Placenta
MH  - Pregnancy
MH  - *Pregnancy Complications, Infectious
MH  - Pregnancy Outcome
MH  - *Zika Virus/genetics
MH  - *Zika Virus Infection
PMC - PMC9380952
COIS- The authors have declared that no competing interests exist.
EDAT- 2022/08/05 06:00
MHDA- 2022/08/19 06:00
PMCR- 2022/08/04
CRDT- 2022/08/04 14:04
PHST- 2022/04/13 00:00 [received]
PHST- 2022/06/29 00:00 [accepted]
PHST- 2022/08/16 00:00 [revised]
PHST- 2022/08/05 06:00 [pubmed]
PHST- 2022/08/19 06:00 [medline]
PHST- 2022/08/04 14:04 [entrez]
PHST- 2022/08/04 00:00 [pmc-release]
AID - PNTD-D-22-00439 [pii]
AID - 10.1371/journal.pntd.0010623 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2022 Aug 4;16(8):e0010623. doi: 10.1371/journal.pntd.0010623. 
      eCollection 2022 Aug.