Infection Dynamics of Dengue Virus in Caco-2 Cells Depending on Its Differentiation Status

Dengue virus (DENV), from the Flaviviridae family, is the causative agent of dengue fever and poses a significant global health challenge. The virus primarily affects the vascular system and liver; however, a growing body of evidence suggests its involvement in the gastrointestinal (GI) tract, contributing to clinical symptoms such as abdominal pain, vomiting, and diarrhea. However, the mechanisms underlying DENV infection in the digestive system remain largely unexplored. Prior research has detected viral RNA in the GI tissue of infected animals; however, whether the dengue virus can directly infect human enterocytes remains unclear. In this study, we examine the infectivity of human intestinal cell lines to the dengue virus and their subsequent response. We report that the Caco-2 cell line, a model of human enterocytes, is susceptible to infection and capable of producing viruses. Notably, differentiated Caco-2 cells exhibited a lower infection rate yet a higher level of virus production than their undifferentiated counterparts. These findings suggest that human intestinal cells are a viable target for the dengue virus, potentially elucidating the GI symptoms observed in dengue fever and offering a new perspective on the pathogenetic mechanisms of the virus.