title: Antiviral effect of vitamin A on norovirus infection via modulation of the gut microbiome.
abstract: The effect and underlying mechanism of vitamin A on norovirus infection are largely unknown. This study aimed to investigate how vitamin A administration affects the gut microbiome after norovirus infection. Here, we demonstrate that treatment with either retinol or retinoic acid (RA) inhibits murine norovirus (MNV) replication using both in vitro and in vivo models. Compositional changes in the gut microbiome associated with RA administration and/or norovirus infection were also investigated. Oral administration of RA and/or MNV significantly altered intestinal microbiome profiles. Particularly, bacterial species belonging to the Lactobacillaceae families were remarkably increased by MNV inoculation and RA administration, suggesting that the antiviral effects of RA occur via the modulation of specific microbiota. The antiviral causal effect of Lactobacillus was identified and demonstrated using in vitro models in RAW264.7 cells. The antiviral immune response to MNV was mediated by IFN-β upregulation. This study represents the first comprehensive profiling of gut microbiota in response to RA treatment against norovirus infection. Moreover, we conclude that the abundance of Lactobacillus through gut microbiota modulation by RA is at least partially responsible for norovirus inhibition.
authors.affiliation: Center for Human and Environmental Microbiome, Institute of Health and Environment, School of Public Health, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
authors.forename: Heetae
authors.initials: H
authors.lastname: Lee
authors.affiliation: Center for Human and Environmental Microbiome, Institute of Health and Environment, School of Public Health, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.|N-BIO, Seoul National University, Gwanak-ro, Gwanak-gu, Seoul 151-742, Korea.
authors.forename: GwangPyo
authors.initials: G
authors.lastname: Ko
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D044822:Biodiversity; D017250:Caliciviridae Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000821:virology; D002432:Cecum / Q000382:microbiology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D000071457:DEAD Box Protein 58 / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D007778:Lactobacillus / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D029322:Norovirus / Q000187:drug effects / Q000502:physiology*; D000067996:RAW 264.7 Cells; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects; D014801:Vitamin A / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D012336:RNA, Ribosomal, 16S; D014801:Vitamin A; D014212:Tretinoin; D016899:Interferon-beta; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58