New Insights and Enhanced Human Norovirus Cultivation in Human Intestinal Enteroids
Khalil Ettayebi, Victoria R. Tenge, Nicolás Cortés-Penfield, Sue E. Crawford, Frederick H. Neill, Xi‐Lei Zeng, Xiaomin Yu, B. Vijayalakshmi Ayyar, Douglas G. Burrin, Sasirekha Ramani, Robert L. Atmar, Mary K. Estes
Abstract
Human noroviruses (HuNoVs) are highly contagious and cause acute and sporadic diarrheal illness in all age groups. In addition, chronic infections occur in immunocompromised cancer and transplant patients. These viruses are antigenically and genetically diverse, and there are strain-specific differences in binding to cellular attachment factors. In addition, new discoveries are being made on strain-specific differences in virus entry and replication and the epithelial cell response to infection in human intestinal enteroids. Human intestinal enteroids are a biologically relevant model to study HuNoVs; however, not all strains can be cultivated at this time. A complete understanding of HuNoV biology thus requires cultivation conditions that will allow the replication of multiple strains. We report optimization of HuNoV cultivation in human intestinal enteroid cultures to increase the numbers of cultivatable strains and the magnitude of replication, which is critical for testing antivirals, neutralizing antibodies, and methods of virus inactivation.