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. 2014 Oct 14;29(5):291–298. doi: 10.1007/s12250-014-3464-4

Effect of amino acid mutation at position 127 in 3A of a rabbit-attenuated foot-and-mouth disease virus serotype Asia1 on viral replication and infection

Aiguo Xin 1,✉, Mingwang Zhu 2, Qi Hu 1, Haisheng Miao 1, Zhenqi Peng 2, Yuwen He 1, Lin Gao 1, Huachun Li 1,✉
PMCID: PMC8206440  PMID: 25326348

Abstract

An amino acid mutation (R127→I) in the 3A non-structural protein of an FMDV serotype Asia1 rabbit-attenuated ZB strain was previously found after attenuation of the virus. To explore the effects of this mutation on viral replication and infection, the amino acid residue isoleucine (I) was changed to arginine (R) in the infectious cDNA clone of the rabbit-attenuated ZB strain by sitedirected mutagenesis, and the R127-mutated virus was rescued. BHK monolayer cells and suckling mice were inoculated with the R127-mutated virus to test its growth property and pathogenicity, respectively. The effects of the R127 mutation on viral replication and virulence were analyzed. The data showed that there was a slight difference in plaque morphology between the R127-mutated and wild-type viruses. The growth rate of the mutated virus was lower in BHK-21 cells and its virulence in suckling mice was also attenuated. This study indicates that the R127 mutation in 3A may play an important role in FMDV replication in vitro and in pathogenicity in suckling mice.

Keywords: foot-and-mouth disease virus (FMDV), 3A protein, mutation, replication ability, virulence

Contributor Information

Aiguo Xin, Phone: +86-871-65015606, FAX: +86-871-65010043, Email: aiguo_xin@hotmail.com.

Huachun Li, Phone: +86-871-65015606, FAX: +86-871-65010043, Email: huachun_li@hotmail.com.

References

  1. Alexandersen S, Mowat N. Foot-and-mouth disease: host range and pathogenesis. Curr Top Microbiol Immunol. 2005;288:9–42. doi: 10.1007/3-540-27109-0_2. [DOI] [PubMed] [Google Scholar]
  2. Beard C W, Mason P W. Genetic determinants of altered virulence of Taiwanese foot-and-mouth disease virus. J Virol. 2000;74:987–991. doi: 10.1128/JVI.74.2.987-991.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Belsham G J. Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure. Prog Biophys Mol Biol. 1993;60:241–260. doi: 10.1016/0079-6107(93)90016-D. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carrillo C, Tulman E R, Delhon G, Lu Z, Carreno A, Vagnozzi A, Kutish G F, Rock D L. Comparative genomics of footand-mouth disease virus. J Virol. 2005;79:6487–6504. doi: 10.1128/JVI.79.10.6487-6504.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Domingo E, Escarmis C, Baranowski E, Ruiz-Jarabo C M, Carrillo E, Nunez J I, Sobrino F. Evolution of foot-and-mouth disease virus. Virus Res. 2003;91:47–63. doi: 10.1016/S0168-1702(02)00259-9. [DOI] [PubMed] [Google Scholar]
  6. Du J, Chang H, Cong G, Shao J, Lin T, Shang Y, Liu Z, Liu X, Cai X, Xie Q. Complete nucleotide sequence of a Chinese serotype Asia1 vaccine strain of foot-and-mouth disease virus. Virus Genes. 2007;35:635–642. doi: 10.1007/s11262-007-0126-8. [DOI] [PubMed] [Google Scholar]
  7. Giraudo A T, Beck E, Strebel K, de Mello P A, La Torre J L, Scodeller E A, Bergmann I E. Identification of a nucleotide deletion in parts of polypeptide 3A in two independent attenuated aphthovirus strains. Virology. 1990;177:780–783. doi: 10.1016/0042-6822(90)90549-7. [DOI] [PubMed] [Google Scholar]
  8. Gladue D P, O’Donnell V, Baker-Bransetter R, Pacheco J M, Holinka L G, Arzt J, Pauszek S, Fernandez-Sainz I, Fletcher P, Brocchi E, Lu Z, Rodriguez L L, Borca M V. Interaction of foot-and-mouth disease virus non-structural protein 3A with host protein DCTN3 is important for viral virulence in cattle. J Virol. 2014;88(5):2737–2747. doi: 10.1128/JVI.03059-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grubman M J, Baxt B. Foot-and-mouth disease. Clin Microbiol Rev. 2004;17:465–493. doi: 10.1128/CMR.17.2.465-493.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Knowles N J, Davies P R, Henry T, O’Donnell V, Pacheco J M, Mason P W. Emergence in Asia of foot-and-mouth disease viruses with altered host range: characterization of alterations in the 3A protein. J Virol. 2001;75:1551–1556. doi: 10.1128/JVI.75.3.1551-1556.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Li S, Gao M, Zhang R, Song G, Song J, Liu D, Cao Y, Li T, Ma B, Liu X, Wang J. A mutant of infectious Asia 1 serotype foot-and-mouth disease virus with the deletion of 10-amino-acid in the 3A protein. Virus Genes. 2010;41:406–413. doi: 10.1007/s11262-010-0529-9. [DOI] [PubMed] [Google Scholar]
  12. Nunez J I, Baranowski E, Molina N, Ruiz-Jarabo C M, Sanchez C, Domingo E, Sobrino F. A single amino acid substitution in nonstructural protein 3A can mediate adaptation of foot-andmouth disease virus to the guinea pig. J Virol. 2001;75:3977–3983. doi: 10.1128/JVI.75.8.3977-3983.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pacheco J M, Henry T M, O’Donnell V K, Gregory J B, Mason P W. Role of nonstructural proteins 3A and 3B in host range and pathogenicity of foot-and-mouth disease virus. J Virol. 2003;77:13017–13027. doi: 10.1128/JVI.77.24.13017-13027.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pacheco J M, Gladue D P, Holinka L G, Arzt J, Bishop E, Smoliga G, Pauszek S J, Bracht A J, O’Donnell V, Fernandez-Sainz I, Fletcher P, Piccone M E, Rodriguez L L, Borca M V. A partial deletion in non-structural protein 3A can attenuate footand-mouth disease virus in cattle. Virology. 2013;446:260–267. doi: 10.1016/j.virol.2013.08.003. [DOI] [PubMed] [Google Scholar]
  15. Ryan M D, Belsham G J, King A M. Specificity of enzyme-substrate interactions in foot-and-mouth disease virus polyprotein processing. Virology. 1989;173:35–45. doi: 10.1016/0042-6822(89)90219-5. [DOI] [PubMed] [Google Scholar]
  16. Valarcher J F, Knowles N J, Zakharov V, Scherbakov A, Zhang Z, Shang Y J, Liu Z X, Liu X T, Sanyal A, Hemadri D, Tosh C, Rasool T J, Pattnaik B, Schumann K R, Beckham T R, Linchongsubongkoch W, Ferris N P, Roeder P L, Paton D J. Multiple origins of foot-and-mouth disease virus serotype Asia 1 outbreaks, 2003–2007. Emerg Infect Dis. 2009;15:1046–1051. doi: 10.3201/eid1507.081621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Xin A, Li H, Li L, Liao D, Yang Y, Zhang N, Chen B. Genome analysis and development of infectious cDNA clone of a virulence-attenuated strain of foot-and-mouth disease virus type Asia 1 from China. Vet Microbiol. 2009;138:273–280. doi: 10.1016/j.vetmic.2009.04.009. [DOI] [PubMed] [Google Scholar]
  18. Xin A, Zhu M, Peng Z, Hu Q, Shi C, Liao D, Wang J, Li H. Int J Genomic. 2014. Genomic changes in an attenuated ZB strain of foot-and-mouth disease virus serotype Asia1 and comparison with its virulent parental strain. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Xue M, Wang H, Li W, Zhou G, Tu Y, Yu L. Effects of amino acid substitutions in the VP2 B-C loop on antigenicity and pathogenicity of serotype Asia1 foot-and-mouth disease virus. Virol J. 2012;9:191–201. doi: 10.1186/1743-422X-9-191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zeng J, Wang H, Xie X, Li C, Zhou G, Yang D, Yu L. Ribavirin-Resistant Variants of Foot-and-Mouth Disease Virus: the Effect of Restricted Quasispecies Diversity on Viral Virulence. J Virol, 88: 4008–4020. [DOI] [PMC free article] [PubMed]

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