Timing of gestational exposure to Zika virus is associated with postnatal growth restriction in a murine model

Abstract

These findings demonstrate that postnatal effects of infection occurring at single time points continue to be detrimental to offspring in the postnatal period in a subset of littermates and subject to a window of gestational susceptibility coinciding with placentation. This model recapitulates frequently encountered clinical scenarios in nonendemic regions, including the majority of the United States, where travel-related exposure occurs in short and well-defined windows of gestation. Our low rate of infection and relatively rare evidence of congenital Zika syndrome parallels human population-based data.

Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

“…Mean CRL did not differ significantly (Student’s t-test) between fetuses of ZIKV-PR-IC- or PBS-inoculated dams ( p -value = 0.22, t- value = 1.23, df = 54), whereas there was a statistically significant (Student’s t-test) reduction in mean CRL between fetuses whose dams were inoculated with ZIKV-PR-IC vs. ZIKV-PR-N139S ( p -value <0.0001, t -value = 5.42, df = 34; Fig 2b). This lack of evidence of severe IUGR for ZIKV-PR-IC is contrary to other studies in which fetuses developed severe IUGR 16,17,20 ; however, this may be due to differences in timing of challenge and necropsy 21 , virus strain, or a different standard for characterizing grossly normal fetuses compared to those in a stage of resorption at a later embryonic age.…”

Zika viruses of African and Asian lineages cause fetal harm in a mouse model of vertical transmission

“…This lack of apparent IUGR for ZIKV-PR-IC is contrary to other studies using Asian-lineage ZIKVs in which fetuses developed severe IUGR [22,28,30]. Again, this disparity may be the result of differences in timing of challenge and necropsy [31], subtle phenotypic differences in virus strain, dose and/or route of inoculation, or metrics for defining grossly normal fetuses compared to those undergoing resorption at a later embryonic age. Critically, the rates of resorption between ZIKV-PR-IC and ZIKV-PR-N139S were not significantly different and are consistent with the rates reported by Miner et al [28].…”

Does the human placenta express the canonical cell entry mediators for SARS-CoV-2?

“…Given that the main mediators for cell entry of SARS-CoV-2 were minimally expressed by the human placenta, we also investigated whether the receptors for congenital viruses such as CMV ( Stegmann and Carey, 2002 ; Arechavaleta-Velasco et al, 2002 ; Aronoff et al, 2017 ; Pereira et al, 2017 ; Al-Haddad et al, 2019 ; Faure Bardon et al, 2020 ) and ZIKV ( Coyne and Lazear, 2016 ; Adams Waldorf et al, 2016 ; Aldo et al, 2016 ; Cao et al, 2017 ; Aagaard et al, 2017 ; Mysorekar, 2017 ; Valentine et al, 2018 ; Adams Waldorf et al, 2018 ; Dudley et al, 2018 ; Walker et al, 2019 ; Nelson et al, 2020 ), which are known to infect and cross the placenta, were detectable using our pipeline. Known receptors for CMV include NRP2 ( Martinez-Martin et al, 2018 ), PDFGRA ( Martinez-Martin et al, 2018 ), and CD46 ( Stein et al, 2019 ).…”