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Published in: Archives of Virology 12/2016

01-12-2016 | Original Article

Apigenin inhibits African swine fever virus infection in vitro

Authors: Astghik Hakobyan, Erik Arabyan, Aida Avetisyan, Liana Abroyan, Lina Hakobyan, Hovakim Zakaryan

Published in: Archives of Virology | Issue 12/2016

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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.
Literature
1.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
2.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
3.
go back to reference 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 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.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
6.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
9.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
10.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
13.
17.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
19.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
20.
go back to reference 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 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
21.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
22.
go back to reference Potterat O, Hamburger M (2008) Drug discovery and development with plant-derived compounds. Prog Drug Res 65:47–118 Potterat O, Hamburger M (2008) Drug discovery and development with plant-derived compounds. Prog Drug Res 65:47–118
25.
26.
go back to reference 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 CrossRef 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 CrossRef
27.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
29.
go back to reference Terahara N (2015) Flavonoids in foods: a review. Nat Prod Commun 10:521–528PubMed Terahara N (2015) Flavonoids in foods: a review. Nat Prod Commun 10:521–528PubMed
31.
go back to reference Tulman ER, Delhon GA, Ku BK, Rock DL (2009) African swine fever virus. Curr Top Microbiol Immunol 328:43–87PubMed Tulman ER, Delhon GA, Ku BK, Rock DL (2009) African swine fever virus. Curr Top Microbiol Immunol 328:43–87PubMed
33.
go back to reference 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 CrossRefPubMedPubMedCentral 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 CrossRefPubMedPubMedCentral
34.
37.
go back to reference 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 CrossRefPubMed 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 CrossRefPubMed
Metadata
Title
Apigenin inhibits African swine fever virus infection in vitro
Authors
Astghik Hakobyan
Erik Arabyan
Aida Avetisyan
Liana Abroyan
Lina Hakobyan
Hovakim Zakaryan
Publication date
01-12-2016
Publisher
Springer Vienna
Published in
Archives of Virology / Issue 12/2016
Print ISSN: 0304-8608
Electronic ISSN: 1432-8798
DOI
https://doi.org/10.1007/s00705-016-3061-y

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