Human norovirus exhibits strain-specific sensitivity to host interferon pathways in human intestinal enteroids

• DOI: 10.1073/pnas.2010834117
• Publication Date: 2020-09-09T23:55:33Z
• Authors: Shih-Ching Lin; Lin Qu; Khalil Ettayebi; Sue E. Crawford; Sarah E. Blutt; Matthew J. Robertson; Xi-Lei Zeng; Victoria R. Tenge; B. Vijayalakshmi ...; Umesh C. Karandikar; Xiaomin Yu; Cristian Coarfa; Robert L. Atmar; Sasirekha Ramani; Mary K. Estes
• Keywords: Strain (injury)

Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis worldwide; yet currently, no vaccines or FDA-approved antiviral drugs available to counter these pathogens. To understand HuNoV biology and epithelial response infection, we performed transcriptomic analyses, RT-qPCR, CRISPR-Cas9 modification human intestinal enteroid (HIE) cultures, functional studies with two virus strains (a pandemic GII.4 a bile acid-dependent GII.3 strain). We identified predominant type III interferon (IFN)-mediated innate infection. Replication both is sensitive exogenous addition IFNs, suggesting potential IFNs as therapeutics. obtain insight into IFN pathway genes that play role in HuNoVs, developed knockout (KO) HIE lines for alpha lambda receptors signaling molecules, MAVS, STAT1, STAT2 An unexpected differential enhanced replication spread was observed GII.3, but not globally dominant STAT1-knockout HIEs compared parental HIEs. These results indicate cellular responses restrict replication. The strain-specific sensitivities against provide one explanation why infections more widespread highlight strain specificity an important factor biology. Genetically modified immune useful tools studying microbial