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- Title
Zika virus diversity in mice is maintained during early vertical transmission from placenta to fetus, but reduced in fetal bodies and brains at late stages of infection.
- Authors
Evans, Alyssa B.; Winkler, Clayton W.; Anzick, Sarah L.; Ricklefs, Stacy M.; Sturdevant, Dan E.; Peterson, Karin E.
- Abstract
Since emerging in French Polynesia and Brazil in the 2010s, Zika virus (ZIKV) has been associated with fetal congenital disease. Previous studies have compared ancestral and epidemic ZIKV strains to identify strain differences that may contribute to vertical transmission and fetal disease. However, within-host diversity in ZIKV populations during vertical transmission has not been well studied. Here, we used the established anti-interferon treated Rag1-/- mouse model of ZIKV vertical transmission to compare genomic variation within ZIKV populations in matched placentas, fetal bodies, and fetal brains via RNASeq. At early stages of vertical transmission, the ZIKV populations in the matched placentas and fetal bodies were similar. Most ZIKV single nucleotide variants were present in both tissues, indicating little to no restriction in transmission of ZIKV variants from placenta to fetus. In contrast, at later stages of fetal infection there was a sharp reduction in ZIKV diversity in fetal bodies and fetal brains. All fetal brain ZIKV populations were comprised of one of two haplotypes, containing either a single variant or three variants together, as largely homogenous populations. In most cases, the dominant haplotype present in the fetal brain was also the dominant haplotype present in the matched fetal body. However, in two of ten fetal brains the dominant ZIKV haplotype was undetectable or present at low frequencies in the matched placenta and fetal body ZIKV populations, suggesting evidence of a strict selective bottleneck and possible selection for certain variants during neuroinvasion of ZIKV into fetal brains. Author summary: Zika virus (ZIKV) is known to cause congenital disease in humans through vertical transmission of the virus from mothers to fetuses during pregnancy. How the virus populations change during this process is currently not well understood. To evaluate differences in ZIKV populations during vertical transmission, we infected pregnant mice with ZIKV and sequenced the viral populations from matched placentas and fetal bodies at early stages of vertical transmission, and matched placentas, fetal bodies, and fetal brains at late stages of vertical transmission when the virus enters the fetal brain. We determined that there is little restriction of ZIKV diversity during transmission from the placenta to the fetus at early stages. However, there was a sharp decrease in ZIKV diversity in both fetal bodies and fetal brains at late stages. Two predominant viral variants were found across all fetal brains and most fetal bodies at late stages, suggesting there may be possible selection for certain variants during neuroinvasion of ZIKV into fetal brains.
- Subjects
FRENCH Polynesia; BRAZIL; FETAL brain; VIRUS diversity; ZIKA virus; SINGLE nucleotide polymorphisms; PLACENTA praevia; FETUS
- Publication
PLoS Neglected Tropical Diseases, 2023, Vol 17, Issue 10, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0011657