ORCID
http://orcid.org/https://orcid.org/0000-0002-4301-1928
Date of Award
Spring 5-15-2023
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
Although they globally cause viral gastroenteritis in children, astroviruses are understudied due to the lack of well-defined animal models. While muAstVs chronically infect immunodeficient mice, a culture system and understanding of their pathogenesis is lacking. Here, we describe a platform to cultivate muAstV using air–liquid interface (ALI) cultures derived from mouse enteroids, which support apical infection and release. Chronic muAstV infection occurs in the small intestine and correlates with higher IFN-λ expression. MuAstV stimulates IFN-λ production in ALI, recapitulating our in vivo findings. We demonstrate that goblet cells and enterocytes are targets for chronic muAstV infection in vivo, and that infection is enhanced by parasite co-infection or type 2 cytokine signaling. Depletion of goblet cells from ALI limits muAstV infection in vitro. During chronic infection, muAstV stimulates IFN-λ production in infected cells and induces ISGs throughout the intestinal epithelium in an IFN-λ-receptor-dependent manner. Collectively, our study provides insights into the cellular tropism and innate immune responses to muAstV and establishes an enteroid-based culture system to propagate muAstV in vitro.
Language
English (en)
Chair and Committee
Megan T. Baldridge
Committee Members
Daniel E. Goldberg, Andrew L. Kau, Gabriel Mbalaviele, James B. Skeath,
Recommended Citation
Makimaa, Heyde, "The Role of MAVS and Interferon-Lambda in Regulating Astrovirus and Norovirus Infections" (2023). Arts & Sciences Electronic Theses and Dissertations. 2883.
https://openscholarship.wustl.edu/art_sci_etds/2883