Intestinal epithelia activate anti-viral signaling via intracellular sensing of rotavirus structural components.
Rotavirus (RV), a leading cause of severe diarrhea, primarily infects intestinal epithelial cells (IECs) causing self-limiting illness. To better understand innate immunity to RV, we sought to define the extent to which IEC activation of anti-viral responses required viral replication or could be recapitulated by inactivated RV or its components. Using model human intestinal epithelia, we observed that RV-induced activation of signaling events and gene expression typically associated with viral infection was largely mimicked by administration of ultraviolet (UV)-inactivated RV. Use of anti-interferon (IFN) neutralizing antibodies revealed that such replication-independent anti-viral gene expression required type I IFN signaling. In contrast, RV-induction of nuclear factor-κB-mediated interleukin-8 expression was dependent on viral replication. The anti-viral gene expression induced by UV-RV was not significantly recapitulated by RV RNA or RV virus-like particles although the latter could enter IEC. Together, these results suggest that RV proteins mediate viral entry into epithelial cells leading to intracellular detection of RV RNA that generates an anti-viral response.
Frias
A H
AH
Department of Pathology, Emory University, Atlanta, Georgia, USA.
Vijay-Kumar
M
M
Gentsch
J R
JR
Crawford
S E
SE
Carvalho
F A
FA
Estes
M K
MK
Gewirtz
A T
AT
D019138:Antibodies, Blocking / Q000494:pharmacology; D002460:Cell Line; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D012367:RNA, Viral / Q000276:immunology; D012401:Rotavirus / Q000472:pathogenicity / Q000502:physiology*; D012400:Rotavirus Infections / Q000276:immunology* / Q000821:virology; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D014466:Ultraviolet Rays; D014771:Virion / Q000276:immunology; D038301:Virus Inactivation; D014779:Virus Replication
D019138:Antibodies, Blocking; D007370:Interferon Type I; D016209:Interleukin-8; D016328:NF-kappa B; D012367:RNA, Viral