Induction of dormant HIV-1 by sodium butyrate

Golub, Efim I.; Li, Gongrong; Volsky, David J.

doi:10.1097/00002030-199106000-00004

Cited by 46 publications

(4 citation statements)

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“…It is also possible that some intrinsic proviral genes are upregulated by butyrate, which may be additive or synergistic with the diminished ISG response to provide a net result of increased virus replication in the presence of butyrate. Additionally, butyrate may in some instances directly affect virus replication independent of, or in addition to, its effect on the type I IFN response, as is reported for HIV-1 (76)(77)(78). Further study exploring the multifaceted regulation of the type I IFN response by butyrate and its differential effects on virus infections is warranted.…”

Section: Discussionmentioning

confidence: 91%

Butyrate Reprograms Expression of Specific Interferon-Stimulated Genes

Chemudupati

Kenney

Smith

et al. 2020

J Virol

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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 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 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 pro-viral 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.

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Section: Discussionmentioning

confidence: 91%

Butyrate Reprograms Expression of Specific Interferon-Stimulated Genes

Chemudupati

Kenney

Smith

et al. 2020

J Virol

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“…It is able to activate integrated viral DNA, and the treatment of cells latently infected with Epstein-Barr virus or HIV virus stimulates the synthesis and the expression of viral DNA (18,19). In HeLa cells, butyrate activates "dormant" HIV by acting on the long terminal repeat-regulating element in a dose-dependent manner (20) and in chronically infected lymphoid and monocyte cells by acting on the TATA box (21).…”

mentioning

confidence: 99%

The Effects of Sodium Butyrate on Transcription Are Mediated through Activation of a Protein Phosphatase

Cuisset¹,

Tichonicky²,

Jaffray³

et al. 1997

Journal of Biological Chemistry

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In this study we have investigated the molecular mechanism by which sodium butyrate modulates gene expression when added to cultured cells. As a model system we used hepatoma tissue culture cells in which sodium butyrate treatment increases histone H1°mRNA level and decreases c-myc mRNA level. Because we observed that stimulation of histone H1°gene expression could take place in the absence of protein neosynthesis, we hypothesized that sodium butyrate induced a posttranslational modification of a factor involved in the transcription process. Using different types of well known kinase and phosphatase inhibitors, we studied the implication of kinase or phosphatase activity in this pathway. Interestingly, cell treatment with potent serine-threonine-phosphatase inhibitors, calyculin A or okadaic acid, prevented the regulation of both histone H1°and c-myc gene expressions by sodium butyrate. On the other hand, the tyrosine phosphatase inhibitor, vanadate, or the protein kinase C inhibitor, staurosporine, did not significantly modify sodium butyrate effects. Using protein phosphatase 1 and 2A for in vitro assays, we found a 45% increase of phosphatase activity after cell treatment by sodium butyrate, possibly due to a protein phosphatase 1-type protein phosphatase. These data strongly suggest that signaling pathway(s) triggered by sodium butyrate to modulate gene expression involve(s) a serine-threonine-phosphatase activity.

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“…There is no reason to suppose that experiments with immunodeficiency viruses are any more susceptible to contamination than experiments with other viruses in culture. Nonetheless, literature on the matter has already developed (53)(54)(55)(56)(57)(58)(59)(60)(61). From this point on, the term HIV-1 Bru will indicate the prototype HIV-1 isolated from patient BRU.…”

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confidence: 99%

LAV Revisited: Origins of the Early HIV-1 Isolates from Institut Pasteur

Wain‐Hobson

Vartanian

Mathieu

et al. 1991

Science

200

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Two of the first human immunodeficiency virus type-1 (HIV-1) strains isolated were authenticated by reanalyzing original cultured samples stored at the Collection Nationale de Culture des Microorganismes as well as uncultured primary material. Cloned polymerase chain reaction products were used to analyze coding sequences of the V3 loop in the gp120 glycoprotein. The original isolate HIV-1 Bru, formerly called LAV, was derived from patient BRU. HIV-1 Lai was derived from patient LAI and contaminated a HIV-1 Bru culture between 20 July and 3 August 1983. The culture became, in effect, HIV-1 Lai, identifiable by a unique motif in the V3 loop. Because of this contamination two, rather than one, HIV-1 isolates were sent to the Laboratory of Tumor Cell Biology at the National Cancer Institute on 23 September 1983. Original HIV-1 Bru was indeed present in the sample marked JBB/LAV. However the M2T-/B sample harbored HIV-1 Lai, a strain capable of growing on established cell lines. The striking similarity between HIV-1 Lai (formerly LAV-Bru) and HTLV-3B sequences remains.

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Induction of dormant HIV-1 by sodium butyrate

Cited by 46 publications

References 0 publications

Butyrate Reprograms Expression of Specific Interferon-Stimulated Genes

Butyrate Reprograms Expression of Specific Interferon-Stimulated Genes

The Effects of Sodium Butyrate on Transcription Are Mediated through Activation of a Protein Phosphatase

LAV Revisited: Origins of the Early HIV-1 Isolates from Institut Pasteur

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