To add value to this area of research, Zhiqiang Zhang, PhD, Associate Professor of Transplant Immunology in Surgery, generated intestinal epithelial cell specific DHX15 knockout mice to investigate DHX15 function in vivo. Using short hairpin RNA knockdown in human cells, Zhang demonstrated that DHX15 is required for intestinal inflammation induced by enteric viruses in vitro. Moreover, Zhang specifically examined the in vivo functional role of DHX15 in intestinal antiviral response and concluded that DHX15 is required for controlling RNA-virus induced intestinal inflammation in vivo. Several intestinal diseases, including intestinal bowel disease, entail intestinal inflammation, which is affected by diet, genetics, immunity as well as microbial factors. The role of enteric viruses in intestinal inflammation and intestinal bowel disease is not fully understood and needs to be further investigated. The human intestine is estimated to contain at least 108-1010 virus-like particles per gram; with different enteric viruses likely having varying affinities towards the gut. Research results by Zhang on DHX15, published in Cell Reports in 2021, sheds some light on how enteric viruses influence health and disease. It is likely that efforts will be made soon to develop potential therapeutics targeting DHX15 to alleviate intestinal inflammation. Interestingly, the causative virus for the COVID-19 pandemic SARS-CoV-2 — is an RNA virus that possibly induces intestinal inflammation since the SARS-CoV-2 receptor (angiotensin-converting enzyme 2) is widely expressed in the human intestine. Furthermore, studies have demonstrated fecal samples of COVID-19 patients to be SARS-CoV-2 positive. It is quite likely that SARS-CoV-2 infects the human body via the intestinal tract like enteric viruses in addition to the respiratory route. “Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is an RNA virus that causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA are frequently observed in COVID-19 patients, and SARS-CoV-2 could efficiently infect human intestinal epithelial cells. Thus, our findings on DHX15 in controlling enteric RNA virus-induced intestinal inflammation may provide potential therapeutic applications involving targeting RNA helicase DHX15 to control SARS-CoV-2 and the intestinal inflammation induced by SARS-CoV-2,” said Zhang. The current understanding in the literature of the enteric gut virome is rudimentary. How enteric viruses affect intestinal homeostasis and their effects on inflammation and intestinal diseases needs to be systematically investigated. Future studies on other RNA helicases, including DEAH-box helicases, may shed more light on these important signaling cascades and lead to potentially useful therapeutics.