Abstract:
:Butyrate is an abundant metabolite produced by gut microbiota. While butyrate is a known histone deacetylase inhibitor that activates expression of many genes involved in immune system pathways, its effects on virus infections and on the antiviral type I interferon (IFN) response have not been adequately investigated. We found that butyrate increases cellular infection with viruses relevant to human and animal health, including influenza virus, reovirus, HIV-1, human metapneumovirus, and vesicular stomatitis virus. Mechanistically, butyrate suppresses levels of specific antiviral IFN-stimulated gene (ISG) products, such as RIG-I and IFITM3, in human and mouse cells without inhibiting IFN-induced phosphorylation or nuclear translocation of the STAT1 and STAT2 transcription factors. Accordingly, we discovered that although butyrate globally increases baseline expression of more than 800 cellular genes, it strongly represses IFN-induced expression of 60% of ISGs and upregulates 3% of ISGs. Our findings reveal that there are differences in the IFN responsiveness of major subsets of ISGs depending on the presence of butyrate in the cell environment, and overall, they identify a new mechanism by which butyrate influences virus infection of cells.IMPORTANCE Butyrate is a lipid produced by intestinal bacteria. Here, we newly show that butyrate reprograms the innate antiviral immune response mediated by type I interferons (IFNs). Many of the antiviral genes induced by type I IFNs are repressed in the presence of butyrate, resulting in increased virus infection and replication. Our research demonstrates that metabolites produced by the gut microbiome, such as butyrate, can have complex effects on cellular physiology, including dampening of an inflammatory innate immune pathway resulting in a proviral cellular environment. Our work further suggests that butyrate could be broadly used as a tool to increase growth of virus stocks for research and for the generation of vaccines.
journal_name
J Viroljournal_title
Journal of virologyauthors
Chemudupati M,Kenney AD,Smith AC,Fillinger RJ,Zhang L,Zani A,Liu SL,Anderson MZ,Sharma A,Yount JSdoi
10.1128/JVI.00326-20subject
Has Abstractpub_date
2020-07-30 00:00:00issue
16eissn
0022-538Xissn
1098-5514pii
JVI.00326-20journal_volume
94pub_type
杂志文章abstract:UNLABELLED:The role of NF-κB in influenza A virus (IAV) infection does not reveal a coherent picture, as pro- and also antiviral functions of this transcription factor have been described. To address this issue, we used clustered regularly interspaced short palindromic repeat with Cas9 (CRISPR-Cas9)-mediated genome eng...
journal_title:Journal of virology
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abstract::A host-mediated RNA-editing event allows hepatitis delta virus (HDV) to express two essential proteins, the small delta antigen (HDAg-S) and the large delta antigen (HDAg-L), from a single open reading frame. One or several members of the ADAR (adenosine deaminases that act on RNA) family are thought to convert the ad...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.75.18.8547-8555.2001
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abstract::We previously reported that the cellular transcription factor hypoxia-inducible factor 1α (HIF-1α) binds a hypoxia response element (HRE) located within the promoter of Epstein-Barr virus's (EBV's) latent-lytic switch BZLF1 gene, Zp, inducing viral reactivation. In this study, EBV-infected cell lines derived from gast...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00722-20
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.02356-09
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pub_type: 杂志文章
doi:10.1128/JVI.58.2.592-599.1986
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doi:10.1128/JVI.00704-09
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.00601-08
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abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus 8) is consistently found in Kaposi's sarcoma lesions and in body-cavity-based lymphomas. A 17-kb KSHV lambda clone was obtained directly from a Kaposi's sarcoma lesion. DNA sequence analysis of this clone identified an open reading frame whi...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.3.1984-1991.1997
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.5.4104-4115.1998
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.9.6502-6507.1996
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pub_type: 杂志文章
doi:10.1128/JVI.01866-18
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.01231-12
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.6.3620-3630.1994
更新日期:1994-06-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1128/JVI.01427-07
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journal_title:Journal of virology
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1982-08-01 00:00:00
abstract::The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into fou...
journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.8.3706-3718.2001
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abstract::The herpes simplex virus type 1 (HSV-1) ICP34.5 gene is a neurovirulence gene in mice. In addition, some ICP34.5 mutants have been reported to have a reduced efficiency of induced reactivation as measured by in vitro explantation of latently infected mouse ganglia. However, since spontaneous reactivation is almost non...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.69.5.3033-3041.1995
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.71.9.6928-6934.1997
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.4.1816-1823.2001
更新日期:2001-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:2015-02-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.70.11.8055-8063.1996
更新日期:1996-11-01 00:00:00
abstract::A gene encoding a polypeptide with homology to mammalian vascular endothelial growth factors (VEGFs) has been discovered in the genome of orf virus (OV), a parapoxvirus that affects sheep and goats and, occasionally, humans. The gene is transcribed abundantly early in infection and is found immediately outside the inv...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.1.84-92.1994
更新日期:1994-01-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) uses a variety of chemokine receptors as coreceptors for virus entry, and the ability of the virus to be neutralized by antibody may depend on which coreceptors are used. In particular, laboratory-adapted variants of the virus that use CXCR4 as a coreceptor are highly sensit...
journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.72.3.1886-1893.1998
更新日期:1998-03-01 00:00:00