{"id":51682,"date":"2025-12-24T07:29:01","date_gmt":"2025-12-24T06:29:01","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2025\/12\/24\/mda5-mavs-and-interferon-lambda-signaling-in-the-intestinal-epithelium-limit-murine-astrovirus-infection-heyde-makimaa\/"},"modified":"2025-12-24T07:29:01","modified_gmt":"2025-12-24T06:29:01","slug":"mda5-mavs-and-interferon-lambda-signaling-in-the-intestinal-epithelium-limit-murine-astrovirus-infection-heyde-makimaa","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2025\/12\/24\/mda5-mavs-and-interferon-lambda-signaling-in-the-intestinal-epithelium-limit-murine-astrovirus-infection-heyde-makimaa\/","title":{"rendered":"MDA5-MAVS and interferon-lambda signaling in the intestinal epithelium limit murine astrovirus infection. Heyde Makimaa"},"content":{"rendered":"<div>\n<p><b>Mucosal Immunol<\/b>. 2025 Dec 21:S1933-0219(25)00138-2. doi: 10.1016\/j.mucimm.2025.12.002. Online ahead of print.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Human astroviruses (HAstVs) are a global cause of pediatric gastroenteritis and can cause disseminated infection in immunocompromised hosts. Murine astrovirus (muAstV) causes acute asymptomatic infections in immunocompetent mice and chronic infection in immunodeficient models and has provided important insights into AstV pathogenesis in vivo. MuAstV can protect immunodeficient mice from other enteric viruses via robust induction of antiviral cytokine interferon-lambda (IFN-\u03bb), with recent findings implicating goblet cells and enterocytes as both cell types infected by muAstV as well as potential sources of IFN-\u03bb in vivo. However, the viral sensing pathways that regulate induction of IFN-\u03bb, as well as the specific activity of IFN-\u03bb in viral control and regulation of cellular tropism, remain to be defined for muAstV. Here, we leveraged single-cell RNA sequencing (scRNA-seq) to provide additional evidence of muAstV tropism for multiple intestinal epithelial cells (IECs) including goblet cells and diverse enterocyte types. Significantly, enterocytes appear to serve as the dominant source of IFN-\u03bb in response to muAstV infection. Moreover, we report that this induction of IFN-\u03bb in response to muAstV is regulated by the MDA5-MAVS pathway, with enhanced infection and expansion of infected cell numbers observed when either Mda5 or Mavs is disrupted. Leveraging mice conditionally deficient for Ifnlr1 or Mavs, we characterized the specific cellular requirements for IFN-\u03bb signaling and MAVS to control muAstV infection. While IFN-\u03bb signaling acts predominantly on secretory cells, including goblet cells, to limit muAstV infection, we found that IECs broadly require MAVS to control muAstV but with no specific IEC type implicated, suggesting a potential synergistic requirement across IECs. Our study highlights the MDA5-MAVS-IFN-\u03bb signaling axis as critical for regulation of muAstV infection, providing further insights into the innate immune regulation of this enteric pathogen.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41435889\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=101299742&amp;ff=20251224012900&amp;v=2.18.0.post22+67771e2\">41435889<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1016\/j.mucimm.2025.12.002\">10.1016\/j.mucimm.2025.12.002<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>Mucosal Immunol. 2025 Dec 21:S1933-0219(25)00138-2. doi: 10.1016\/j.mucimm.2025.12.002. Online ahead of print. ABSTRACT Human astroviruses (HAstVs) are a global cause of pediatric gastroenteritis and can cause disseminated infection in immunocompromised hosts. Murine astrovirus (muAstV) causes acute asymptomatic infections in immunocompetent mice and chronic infection in immunodeficient models and has provided important insights into AstV pathogenesis in &#8230; <a title=\"MDA5-MAVS and interferon-lambda signaling in the intestinal epithelium limit murine astrovirus infection. Heyde Makimaa\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2025\/12\/24\/mda5-mavs-and-interferon-lambda-signaling-in-the-intestinal-epithelium-limit-murine-astrovirus-infection-heyde-makimaa\/\" aria-label=\"Read more about MDA5-MAVS and interferon-lambda signaling in the intestinal epithelium limit murine astrovirus infection. Heyde Makimaa\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[57,42],"tags":[],"class_list":["post-51682","post","type-post","status-publish","format-standard","hentry","category-mucosal-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/51682","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=51682"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/51682\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=51682"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=51682"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=51682"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}