Expression of SARS-CoV-2 entry factors, electrolyte and mineral transporters in different mouse intestinal epithelial cell types

Authors: Pearce, Sarah; SUNTORNSARATOON, PANAN - Rutgers University; KISHIDA, KUNIHIRO - Rutgers University; AL-JAWADI, ARWA - Rutgers University; GUADRIA, JOSHUA - Rutgers University; NADLER, IONA - Rutgers University; FLORES, JUAN - Rutgers University; SHIARELLA, RILEY - Rutgers University; AUVINEN, MADELYN - Rutgers University; YU, SHIYAN - Rutgers University; GAO, NAN - Rutgers University; FERRARIS, RONALD - Rutgers University

Submitted to: Physiological Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/13/2021
Publication Date: 11/9/2021
Citation: Pearce, S.C., Suntornsaratoon, P., Kishida, K., Al-Jawadi, A., Guadria, J., Nadler, I., Flores, J., Shiarella, R., Auvinen, M., Gao, N., Ferraris, R.P. 2021. Expression of SARS-CoV-2 entry factors, electrolyte and mineral transporters in different mouse intestinal epithelial cell types. Physiological Reports. 9(21). Article e15061. https://doi.org/10.14814/phy2.15061.
DOI: https://doi.org/10.14814/phy2.15061

Interpretive Summary: SARS-CoV-2 is the virus responsible for the current COVID-19 pandemic. Data shows that it can affect the gastrointestinal tract, including causing diarrhea. Some of the genes coding for virus binding proteins and many ion and mineral transporters are found in the gastrointestinal tract. The virus-related genes may increase infection of specific types of cells within the intestine. The same cells which may express viral-coding genes are also involved in helping to absorb and transport minerals such as iron, and ions such as sodium (salt) to other areas of the body. This paper shows these various SARS-CoV-2 factors and other transporters are differentially expressed in the different intestine cell types. Similarities in expression of its entry factors suggest that SARS-CoV-2 can potentially bind to and influence function in all intestinal cell types. This research is of primary interest to research scientists and medical professionals.

Technical Abstract: Gastrointestinal symptoms including secretory diarrhea are observed in >60 % of COVID-19 patients as SARS-CoV-2 has evolved clever adaptations to breach the small intestinal barrier then interact with transporters. Host angiotensin converting enzyme 2 (ACE2) and proteases facilitating viral entry are highly expressed in the intestine, but there is little information regarding their expression in different small intestinal cell types. Here we compared expression of SARS-CoV-2 entry factors to that of representative mineral and electrolyte transporters known to mediate disruptions in intestinal fluid transport. We tested the hypothesis that SARS-CoV-2 entry factors, electrolyte and mineral transporters are expressed significantly in non-enterocyte cell types by making intestinal organoids enriched in enterocytes (ENT), goblet (GOB), Paneth (PAN) or stem (ISC) cells. mRNA levels of electrolyte transporters DRA, NBCe1 and NHE3 were greatest in ENT, while CFTR and NKCC1 were mainly expressed in ISC and PAN that also displayed immunohistochemically abundant basolateral NKCC1. In contrast, expression of ACE2 and mediators of SARS-CoV-2 entry were homogeneously expressed among cells types. Members of the intestinal transport system for iron were also generally expressed homogeneously among different cell types while those for calcium were highly expressed in PAN. Similarities in expression of its entry factors suggest that SARS-CoV-2 can potentially bind to and influence function in all intestinal cell types. The expression pattern of their transporters indicates that nonenterocytes likely contribute significantly to electrolyte and mineral homeostasis.