Abstract
The SARS-CoV-2 is the causative agent of the COVID-19 pandemic. The data available about COVID-19 during pregnancy have demonstrated placental infection; however, the mechanisms associated with intrauterine transmission of SARS-CoV-2 is still debated. Intriguingly, while canonical SARS-CoV-2 cell entry mediators are expressed at low levels in placental cells, the receptors for viruses that cause congenital infections such as the cytomegalovirus and Zika virus are highly expressed in these cells. Here we analyzed the transcriptional profile (microarray and single-cell RNA-Seq) of proteins potentially interacting with coronaviruses to identify non- canonical mediators of SARS-CoV-2 infection and replication in the placenta. Despite low levels of the canonical cell entry mediators ACE2 and TMPRSS2, we show that cells of the syncytiotrophoblast, villous cytotrophoblast, and extravillous trophoblast co-express high levels of the potential non-canonical cell-entry mediators DPP4 and CTSL. We also found changes in the expression of DAAM1 and PAICS genes during pregnancy, which are translated into proteins also predicted to interact with coronaviruses proteins. These results provide new insight into the interaction between SARS-CoV-2 and host proteins that may act as non-canonical routes for SARS-CoV-2 infection and replication in the placenta cells.
Highlights
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) (Wu et al, 2020)
Recent literature has shown placenta cells infected with SARSCoV-2 in pregnant women diagnosed with moderate to severe COVID-19 (Patanè et al, 2020; Penfield et al, 2020), with findings supporting the vertical transmission of SARS-CoV-2 in early and late pregnancy (Hosier et al, 2020; Patanè et al, 2020; Schwartz and Morotti, 2020; Shende et al, 2021; ValdespinoVázquez et al, 2021)
We demonstrated by transcriptomic analyses and in silico predictions of virus-host protein-protein interactions that, despite low-levels of angiotensinconverting enzyme 2 (ACE2) and TMPRSS2, villous trophoblast cells express high levels of the potential non-canonical cell-entry mediators dipeptidyl peptidase 4 (DPP4) and cathepsin L (CTSL)
Summary
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) (Wu et al, 2020). It was first notified at the end of 2019, in Wuhan, China, and became a worldwide pandemic (Dong E. et al, 2020). For specific groups of COVID-19 patients, for example, pregnant women, the potential impacts of SARS-CoV-2 infection remain mostly unknown, and data are limited. Considering previous works reporting coronaviruses infections (Schwartz and Graham, 2020), pregnant women are at higher risk of SARS-CoV-2 infection due to physiological changes in the immune, cardiorespiratory, and metabolic systems (Qadri and Mariona, 2020)
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