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Apigenin inhibits African swine fever virus infection in vitro

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Abstract

African swine fever virus (ASFV) is one of the most devastating diseases of domestic pigs for which no effective vaccines are available. Flavonoids, natural products isolated from plants, have been reported to have significant in vitro and in vivo antiviral activity against different viruses. Here, we tested the antiviral effect of five flavonoids on the replication of ASFV in Vero cells. Our results showed a potent, dose-dependent anti-ASFV effect of apigenin in vitro. Time-of-addition experiments revealed that apigenin was highly effective at the early stages of infection. Apigenin reduced the ASFV yield by more than 99.99 % when it was added at 1 hpi. The antiviral activity of apigenin was further investigated by evaluation of ASFV protein synthesis and viral factories. This flavonoid inhibited ASFV-specific protein synthesis and viral factory formation. ASFV-infected cells continuously treated with apigenin did not display a cytopathic effect. Further studies addressing the use of apigenin in vivo are needed.

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References

  1. Bastos AD, Penrith ML, Crucière C, Edrich JL, Hutchings G, Roger F, Couacy-Hymann E, Thomson RG (2003) Genotyping field strains of African swine fever virus by partial p72 gene characterisation. Arch Virol 148:693–706. doi:10.1007/s00705-002-0946-8

    Article  CAS  PubMed  Google Scholar 

  2. Calland N, Albecka A, Belouzard S, Wychowski C, Duverlie G, Descamps V, Hober D, Dubuisson J, Rouillé Y, Séron K (2012) (-)-Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry. Hepatology 55:720–729. doi:10.1002/hep.24803

    Article  CAS  PubMed  Google Scholar 

  3. Carrascosa AL, Bustos MJ, de Leon P (2011) Methods for growing and titrating African swine fever virus: field and laboratory samples. Curr Protoc Cell Biol Chapter 26, Unit 26.14

  4. Chiang LC, Chiang W, Liu MC, Lin CC (2003) In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids. J Antimicrob Chemother 52:194–198. doi:10.1093/jac/dkg291

    Article  CAS  PubMed  Google Scholar 

  5. del Val M, Viñuela E (1987) Glycosylated components induced in African swine fever (ASF) virus-infected Vero cells. Virus Res 7:297–308. doi:10.1016/0168-1702(87)90044-X

    Article  PubMed  Google Scholar 

  6. Fabregas J, García D, Fernandez-Alonso M, Rocha AI, Gómez-Puertas P, Escribano JM, Otero A, Coll JM (1999) In vitro inhibition of the replication of haemorrhagic septicaemia virus (VHSV) and African swine fever virus (ASFV) by extracts from marine microalgae. Antiviral Res 44:67–73. doi:10.1016/S0166-3542(99)00049-2

    Article  CAS  PubMed  Google Scholar 

  7. Galindo I, Hernáez B, Berná J, Fenoll J, Cenis JL, Escribano JM, Alonso C (2011) Comparative inhibitory activity of the stilbenes resveratrol and oxyresveratrol on African swinefever virus replication. Antiviral Res 91:57–63. doi:10.1016/j.antiviral.2011.04.013

    Article  CAS  PubMed  Google Scholar 

  8. García-Villalón D, Gil-Fernández C (1991) Antiviral activity of sulfated polysaccharides against African swine fever virus. Antiviral Res 15:139–148. doi:10.1016/0166-3542(91)90031-L

    Article  PubMed  Google Scholar 

  9. Gómez-Puertas P, Rodríguez F, Oviedo JM, Brun A, Alonso C, Escribano JM (1998) The African swine fever virus proteins p54 and p30 are involved in two distinct steps of virus attachment and both contribute to the antibody-mediated protective immune response. Virology 243:461–471. doi:10.1006/viro.1998.9068

    Article  PubMed  Google Scholar 

  10. Ha SY, Youn H, Song CS, Kang SC, Bae JJ, Kim HT, Lee KM, Eom TH, Kim IS, Kwak JH (2014) Antiviral effect of flavonol glycosides isolated from the leaf of Zanthoxylum piperitum on influenza virus. J Microbiol 52:340–344. doi:10.1007/s12275-014-4073-5

    Article  CAS  PubMed  Google Scholar 

  11. Helfer M, Koppensteiner H, Schneider M, Rebensburg S, Forcisi S, Müller C, Schmitt-Kopplin P, Schindler M, Brack-Werner R (2014) The root extract of the medicinal plant Pelargonium sidoides is a potent HIV-1 attachment inhibitor. PLoS One 9:e87487. doi:10.1371/journal.pone.0087487

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hernaez B, Cabezas M, Muñoz-Moreno R, Galindo I, Cuesta-Geijo MA, Alonso C (2013) A179L, a new viral Bcl2 homolog targeting Beclin 1 autophagy related protein. Curr Mol Med 13:305–316. doi:10.2174/156652413804810736

    Article  CAS  PubMed  Google Scholar 

  13. Hernaez B, Escribano JM, Alonso C (2006) Visualization of the African swine fever virus infection in living cells by incorporation into thevirus particle of green fluorescent protein-p54 membrane protein chimera. Virology 350:1–14. doi:10.1016/j.virol.2006.01.021

    Article  CAS  PubMed  Google Scholar 

  14. Hernaez B, Escribano JM, Alonso C (2008) African swine fever virus protein p30 interaction with heterogeneous nuclear ribonucleoprotein K (hnRNP-K) during infection. FEBS Lett 582:3275–3280. doi:10.1016/j.febslet.2008.08.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hernaez B, Alonso C (2010) Dynamin- and clathrin-dependent endocytosis in African swine fever virus entry. J Virol 84:2100–2109. doi:10.1128/JVI.01557-09

    Article  CAS  PubMed  Google Scholar 

  16. Johari J, Kianmehr A, Mustafa MR, Abubakar S, Zandi K (2012) Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus. Int J Mol Sci 13:16785–16795. doi:10.3390/ijms131216785

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Karalova EM, Sargsyan KhV, Hampikian GK, Voskanyan HE, Abroyan LO, Avetisyan AS, Hakobyan LA, Arzumanyan HH, Zakaryan HS, Karalyan ZA (2011) Phenotypic and cytologic studies of lymphoid cells and monocytes in primary culture of porcine bone marrow during infection of African swine fever virus. In Vitro Cell Dev Biol Anim 47:200–204. doi:10.1007/s11626-010-9380-5

    Article  CAS  PubMed  Google Scholar 

  18. Khachatoorian R, Arumugaswami V, Raychaudhuri S, Yeh GK, Maloney EM, Wang J, Dasgupta A, French SW (2012) Divergent antiviral effects of bioflavonoids on the hepatitis C virus life cycle. Virology 433:346–355. doi:10.1016/j.virol.2012.08.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kolokoltsov AA, Adhikary S, Garver J, Johnson L, Davey RA, Vela EM (2012) Inhibition of Lassa virus and Ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin. Arch Virol 157:121–127. doi:10.1007/s00705-011-1115-8

    Article  CAS  PubMed  Google Scholar 

  20. Miguel Ángel CG, Chiappi M, Galindo I, Barrado-Gil L, Muñoz-Moreno R, Carrascosa JL, Alonso C (2015) Cholesterol flux is required for endosomal progression of African swine fever virions during the initial establishment of infection. J Virol 90:1534–1543. doi:10.1128/JVI.02694-15

    Google Scholar 

  21. Murali KS, Sivasubramanian S, Vincent S, Murugan SB, Giridaran B, Dinesh S, Gunasekaran P, Krishnasamy K, Sathishkumar R (2015) Anti-chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon. Asian Pac J Trop Med 8:352–358. doi:10.1016/S1995-7645(14)60343-6

    Article  CAS  PubMed  Google Scholar 

  22. Potterat O, Hamburger M (2008) Drug discovery and development with plant-derived compounds. Prog Drug Res 65:47–118

    Google Scholar 

  23. Qian S, Fan W, Qian P, Zhang D, Wei Y, Chen H, Li X (2015) Apigenin restricts FMDV infection and inhibits viral IRES driven translational activity. Viruses 7:1613–1626. doi:10.3390/v7041613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rodríguez JM, Salas ML (2013) African swine fever virus transcription. Virus Res 173:15–28. doi:10.1016/j.virusres.2012.09.014

    Article  PubMed  Google Scholar 

  25. Sánchez-Vizcaíno JM, Mur L, Gomez-Villamandos JC, Carrasco L (2015) An update on the epidemiology and pathology of African swine fever. J Comp Pathol 152-9-21. doi:10.1016/j.jcpa.2014.09.003

  26. Saotome K, Morita H, Umeda M (1989) Cytotoxicity test with simplified crystal violet staining method using microtitre plates and its application to injection drugs. Toxicol Vitro 3:317–321. doi:10.1016/0887-2333(89)90039-8

    Article  CAS  Google Scholar 

  27. Shibata C, Ohno M, Otsuka M, Kishikawa T, Goto K, Muroyama R, Kato N, Yoshikawa T, Takata A, Koike K (2014) The flavonoid apigenin inhibits hepatitis C virus replication by decreasing mature microRNA122 levels. Virology 462–463:42–48. doi:10.1016/j.virol.2014.05.024

    Article  PubMed  Google Scholar 

  28. Son M, Lee M, Sung GH, Lee T, Shin YS, Cho H, Lieberman PM, Kang H (2013) Bioactive activities of natural products against herpesvirus infection. J Microbiol 51:545–551. doi:10.1007/s12275-013-3450-9

    Article  CAS  PubMed  Google Scholar 

  29. Terahara N (2015) Flavonoids in foods: a review. Nat Prod Commun 10:521–528

    PubMed  Google Scholar 

  30. Tong X, Pelling JC (2013) Targeting the PI3K/Akt/mTOR axis by apigenin for cancer prevention. Anticancer Agents Med Chem 13:971–978. doi:10.2174/18715206113139990119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Tulman ER, Delhon GA, Ku BK, Rock DL (2009) African swine fever virus. Curr Top Microbiol Immunol 328:43–87

    CAS  PubMed  Google Scholar 

  32. Vela EM, Bowick GC, Herzog NK, Aronson JF (2008) Genistein treatment of cells inhibits arenavirus infection. Antiviral Res 77:153–156. doi:10.1016/j.antiviral.2007.09.005

    Article  CAS  PubMed  Google Scholar 

  33. Xu L, Su W, Jin J, Chen J, Li X, Zhang X, Sun M, Sun S, Fan P, An D, Zhang H, Zhang X, Kong W, Ma T, Jiang C (2014) Identification of luteolin as enterovirus 71 and coxsackievirus A16 inhibitors through reporter viruses and cell viability-based screening. Viruses 6:2778–2795. doi:10.3390/v6072778

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Yang ZF, Bai LP, Huang WB, Li XZ, Zhao SS, Zhong NS, Jiang ZH (2014) Comparison of in vitro antiviral activity of tea polyphenols against influenza A and B viruses and structure-activity relationship analysis. Fitoterapia 93:47–53. doi:10.1016/j.fitote.2013.12.011

    Article  CAS  PubMed  Google Scholar 

  35. Zakaryan H, Revilla Y (2016) African swine fever virus: current state and future perspectives in vaccine and antiviral research. Vet Microbiol 185:15–19. doi:10.1016/j.vetmic.2016.01.016

    Article  PubMed  Google Scholar 

  36. Zandi K, Teoh BT, Sam SS, Wong PF, Mustafa MR, Abubakar S (2011) Antiviral activity of four types of bioflavonoid against dengue virus type-2. Virol J 8:560. doi:10.1186/1743-422X-8-560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang L, Cheng X, Gao Y, Zheng J, Xu Q, Sun Y, Guan H, Yu H, Sun Z (2015) Apigenin induces autophagic cell death in human papillary thyroid carcinoma BCPAP cells. Food Funct 6:3464–3472. doi:10.1039/c5fo00671f

    Article  CAS  PubMed  Google Scholar 

  38. Zhang W, Qiao H, Lv Y, Wang J, Chen X, Hou Y, Tan R, Li E (2014) Apigenin inhibits enterovirus-71 infection by disrupting viral RNA association with trans-acting factors. PLoS One 9:e110429. doi:10.1371/journal.pone.0110429

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank ARMACAD for investments in laboratory renovation. We thank Dr. Haig Eskandarian (EPFL, Switzerland) for critical reading and useful comments.

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Correspondence to Hovakim Zakaryan.

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This work was supported by a Grant from the Armenian National Science and Education Fund (Biotech-3751). All authors declare that they have no conflict of interest. This article does not contain any studies with human participants or animals performed by any of the authors.

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Hakobyan, A., Arabyan, E., Avetisyan, A. et al. Apigenin inhibits African swine fever virus infection in vitro . Arch Virol 161, 3445–3453 (2016). https://doi.org/10.1007/s00705-016-3061-y

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