Genistein, a protein tyrosine kinase inhibitor, suppresses the fusogenicity of Moloney murine leukemia virus envelope protein in XC cells

Kubo, Yasuo; Ishimoto, Akinori; Arima, Hiroshi

doi:10.1007/s00705-003-0164-z

Cited by 14 publications

(17 citation statements)

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“…A review of the current literature has indicated that flavonoids affect virus binding to cell membranes, entry into the cell, replication, viral protein translation within the host cell, and formation of certain glycoprotein complexes of the virus envelope [8]. At the host cell level, isoflavones, mainly genistein but not daidzein, can affect the induction of certain transcription factors and secretion of cytokines; most of these effects have been attributed to a reduction in protein tyrosine kinase activity [18]. Kae and its derivatives have been tested for their potential antiviral properties including reducing herpes simplex virus-1 and poliovirus infection at 0.4 mM and <10 µM, respectively [19], [20].…”

Section: Discussionmentioning

confidence: 99%

Anti- Japanese-Encephalitis-Viral Effects of Kaempferol and Daidzin and Their RNA-Binding Characteristics

Zhang

Wú

et al. 2012

PLoS ONE

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BackgroundNew therapeutic tools and molecular targets are needed for treatment of Japanese encephalitis virus (JEV) infections. JEV requires an α-1 translational frameshift to synthesize the NS1' protein required for viral neuroinvasiveness. Several flavonoids have been shown to possess antiviral activity in vitro against a wide spectrum of viruses. To date, the antiviral activities of flavonol kaempferol (Kae) and isoflavonoid daidzin (Dai) against JEV have not been described.Methodology/Principal FindingsThe 50% cytotoxic concentration (CC50) and 50% effective concentration (EC50) against JEV were investigated in BHK21 cells by MTS reduction. Activity against viral genomic RNA and proteins was measured by real-time RT-PCR and western blotting. The frameshift site RNA-binding characterization was also determined by electrospray ionization mass spectrometry, isothermal titration calorimetry and autodocking analysis. EC50 values of Kae and Dai were 12.6 and 25.9 µM against JEV in cells pretreated before infection, whereas in cells infected before treatment, EC50 was 21.5 and 40.4 µM, respectively. Kae exhibited more potent activity against JEV and RNA binding in cells following internalization through direct inhibition of viral replication and protein expression, indicating that its antiviral activity was principally due to direct virucidal effects. The JEV frameshift site RNA (fsRNA) was selected as a target for assaying Kae and Dai. ITC of fsRNA revealed an apparent Kb value for Kae that was nine fold stronger than that for Dai. This binding was confirmed and localized to the RNA using ESI-MS and autodock analysis. Kae could form non-covalent complexes with fsRNA more easily than Dai could.Conclusions/SignificanceKae demonstrates more potent antiviral activity against JEV than does Dai. The mode of action of Kae as an anti-JEV agent seems to be related to its ability to inactivate virus by binding with JEV fsRNA.

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Section: Discussionmentioning

confidence: 99%

Anti- Japanese-Encephalitis-Viral Effects of Kaempferol and Daidzin and Their RNA-Binding Characteristics

Zhang

Wú

et al. 2012

PLoS ONE

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“…This result allows us to make a functional differentiation between these two poxviruses at the level of entry into cancer cells. The role of isoflavones like genistein at inhibiting the replication of many distinct viruses has been well documented, ranging from virus binding, (Andres et al, 2007; Hayashi et al, 1997) and entry (Kubo et al, 2003; Li et al, 2000; Sharma-Walia et al, 2004) to virus replication (Evers et al, 2005; Kim et al, 2006; Robin et al, 2001; Yura et al, 1993), viral protein translation, as well as the formation of viral glycoproteins complexes (Andres et al, 2007). Here we show that the kinase targets for genistein are required at very different levels for VACV (i.e.…”

Section: Discussionmentioning

confidence: 99%

Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

et al. 2010

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Myxoma (MYXV) and vaccinia virus (VACV) have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1- Low pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2- The tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3- Knockdown of PAK1 revealed that it is required for a late stage downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.

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“…Flavonoids, including genistein, reduced the infectivity of nonenveloped viruses, including the following: single-stranded RNA poliovirus, coxsackie virus and echovirus from the Picornaviridae family [44,50,[55][56][57][58]; double-stranded RNA viruses such as rotavirus [59] and double-stranded DNA viruses including adenovirus [33,34]; and John Cunningham (JC) virus [48] and simian virus 40 (SV40) [54] from the Adenoviridae and Polyomaviridae (JC and SV40) families ( Table 1). Flavonoids also inhibited the infectivity of a variety of enveloped viruses such as single-stranded RNA viruses in the Reoviridae, Arenaviridae, Flaviviridae, Coronaviridae, Ret-roviridae [both human immunodeficiency virus (HIV) and Moloney murine leukemia virus (MoMLV)], Arteriviridae and Paramyxoviridae families, including arenavirus [35], bovine viral diarrhea virus [37], coronavirus [38], HIV [47], MoMLV [49], porcine reproductive and respiratory syndrome (PRRS) virus [51] and respiratory syncytial virus [52]; and double-stranded DNA viruses, including bovine herpes virus (BHV) [36], Epstein-Barr virus (EBV) [39], herpes simplex virus (HSV) 1 [34,40,41,44] and HSV-2 [41], herpes human virus (HHV) 8 [46] and human cytomegalovirus (CMV) [45,60] from the Herpesviridae family.…”

Section: Antiviral Activity Of Isoflavonesmentioning

confidence: 99%

Soy isoflavones and virus infections

Andres

Donovan

Kuhlenschmidt

2009

The Journal of Nutritional Biochemistry

111

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Isoflavones and their related flavonoid compounds exert antiviral properties in vitro and in vivo against a wide range of viruses. Genistein is, by far, the most studied soy isoflavone in this regard, and it has been shown to inhibit the infectivity of enveloped or nonenveloped viruses, as well as single-stranded or double-stranded RNA or DNA viruses. At concentrations ranging from physiological to supraphysiological (3.7-370 muM), flavonoids, including genistein, have been shown to reduce the infectivity of a variety of viruses affecting humans and animals, including adenovirus, herpes simplex virus, human immunodeficiency virus, porcine reproductive and respiratory syndrome virus, and rotavirus. Although the biological properties of the flavonoids are well studied, the mechanisms of action underlying their antiviral properties have not been fully elucidated. Current results suggest a combination of effects on both the virus and the host cell. Isoflavones have been reported to affect virus binding, entry, replication, viral protein translation and formation of certain virus envelope glycoprotein complexes. Isoflavones also affect a variety of host cell signaling processes, including induction of gene transcription factors and secretion of cytokines. The efficacy of isoflavones and related flavonoids in virus infectivity in in vitro bioassays is dependent on the dose, frequency of administration and combination of isoflavones used. Despite promising in vitro results, there is lack of data confirming the in vivo efficacy of soy isoflavones. Thus, investigations using appropriate in vivo virus infectivity models to examine pharmacological and especially physiological doses of flavonoids are warranted.

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Genistein, a protein tyrosine kinase inhibitor, suppresses the fusogenicity of Moloney murine leukemia virus envelope protein in XC cells

Cited by 14 publications

References 50 publications

Anti- Japanese-Encephalitis-Viral Effects of Kaempferol and Daidzin and Their RNA-Binding Characteristics

Anti- Japanese-Encephalitis-Viral Effects of Kaempferol and Daidzin and Their RNA-Binding Characteristics

Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

Soy isoflavones and virus infections

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