Inhibition of the Epstein–Barr virus lytic cycle by moronic acid

Chang, Fang Rong; Hsieh, Yi Chung; Chang, Yung Fu; Lee, Kuo Hsiung̀; Wu, Yang Chang; Chang, Li

doi:10.1016/j.antiviral.2009.12.002

Cited by 41 publications

(35 citation statements)

References 36 publications

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“…9). Our findings are consistent with studies showing that the EBV lytic cycle is inhibited by saturated and unsaturated long-chain fatty acids (66), as well as the lipophilic small molecules moronic acid and resveratrol (67,68). The blocking of EBV reactivation by lipophilic molecules may be mediated by a receptor that recognizes lipophilic molecules or by interactions between the fatty acids and lipids in the cell membrane generating a cellular response that prevents triggering of the EBV lytic cycle.…”

Section: Discussionsupporting

confidence: 80%

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

Gorres

Daigle

Mohanram

et al. 2014

J Virol

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The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short-and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. IMPORTANCELytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota. Small-molecule inducers of the lytic cycle are desired for oncolytic therapy. Inhibition of viral reactivation, alternatively, may prove useful in cancer treatment. Overall, our findings contribute to the understanding of pathways that control the latent-to-lytic switch and identify naturally occurring molecules that may regulate this process.

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Section: Discussionsupporting

confidence: 80%

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

Gorres

Daigle

Mohanram

et al. 2014

J Virol

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“…BP-AF-08 has also been shown to exhibit a variety of biological activities, including anti-HIV [10], antiinfluenza virus [19] and anti-herpes virus [20] actions. It has also been reported that moronic acid, an important component of this propolis, shows anti-viral [21][22][23][24][25] and cytotoxic [26] activities. Furthermore, we are going to isolate the active components from BP-AF-08.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Brazilian Propolis on Tumor Promotion in Two-Stage Mouse Skin Carcinogenesis

Yasukawa¹

2012

J. Pharm. Nutr. Sci.

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Propolis is produced by honeybees and has many biological properties, including immunomodulatory, antiinflammatory, anti-oxidant, anti-bacterial, anti-viral and anti-cancer actions. Five ethanol extracts of Brazilian propolis were tested for inhibition of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. The ethanol extract of Brazilian propolis AF-08 markedly inhibited TPA-induced inflammatory ear edema in mice. This extract suppressed tumor promotion by TPA following initiation with 7,12-dimethylbenz[a]anthracene (DMBA) in mouse skin. Moronic acid, a major component of Brazilian propolis AF-08, markedly inhibited two-stage carcinogenesis by DMBA plus TPA. These results suggest that Brazilian propolis AF-08 contributes to the prevention of cancer.

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“…Real-time quantitative PCR was performed according to the method as described (41). Primers used for amplification of BRLF1 and actin were described earlier (59).…”

Section: Methodsmentioning

confidence: 99%

Role of RNF4 in the Ubiquitination of Rta of Epstein-Barr Virus

Yang

Yoshikai

Hsu

et al. 2013

Journal of Biological Chemistry

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Background: Rta is a transcription factor encoded by Epstein-Barr virus (EBV) that activates the transcription of vial lytic genes and promotes lytic development. Results: RNF4 enhances the ubiquitination of Rta, thus decreasing lytic replication and virions production. Conclusion: RNF4 targets SUMO-2-conjugated Rta and promotes Rta ubiquitination. Significance: RNF4 is a SUMO-targeted ubiquitin ligase of Rta that modulates the amount of Rta during EBV lytic progression.

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Inhibition of the Epstein–Barr virus lytic cycle by moronic acid

Cited by 41 publications

References 36 publications

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

Inhibitory Effects of Brazilian Propolis on Tumor Promotion in Two-Stage Mouse Skin Carcinogenesis

Role of RNF4 in the Ubiquitination of Rta of Epstein-Barr Virus

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