Effects of two amino acid substitutions in the capsid proteins on the interaction of two cell-adapted PanAsia-1 strains of foot-and-mouth disease virus serotype O with heparan sulfate receptor

被引：18

作者：

Bai, Xingwen ^{[1
]}

Bao, Huifang ^{[1
]}

Li, Pinghua ^{[1
]}

Wei, Wei ^{[1
]}

Zhang, Meng ^{[1
]}

Sun, Pu ^{[1
]}

Cao, Yimei ^{[1
]}

Lu, Zengjun ^{[1
]}

Fu, Yuanfang ^{[1
]}

Xie, Baoxia ^{[1
]}

Chen, Yingli ^{[1
]}

Li, Dong ^{[1
]}

Luo, Jianxun ^{[1
]}

Liu, Zaixin ^{[1
]}

机构：

[1] Chinese Acad Agr Sci, Engn Res Ctr Biol Detect Gansu Prov, Lanzhou Vet Res Inst, OIE Natl Foot & Mouth Dis Reference Lab,State Key, Lanzhou 730046, Gansu, Peoples R China

来源：

VIROLOGY JOURNAL | 2014年 / 11卷

基金：

国家高技术研究发展计划(863计划);

关键词：

Foot-and-mouth disease virus; PanAsia-1; strain; Heparan sulfate receptor; Phenotypic property; Molecular determinant; SWISS-MODEL; INTEGRIN ALPHA(V)BETA(3); OLIGOSACCHARIDE RECEPTOR; RESISTANT MUTANTS; BINDING; CULTURE; RECOGNITION; SEQUENCE; SITE; REPLICATION;

D O I：

10.1186/1743-422X-11-132

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Background: Some cell-adapted strains of foot-and-mouth disease virus (FMDV) can utilize heparan sulfate (HS) as a receptor to facilitate viral infection in cultured cells. A number of independent sites on the capsid that might be involved in FMDV-HS interaction have been studied. However, the previously reported residues do not adequately explain HS-dependent infection of two cell-adapted PanAsia-1 strains (O/Tibet/CHA/6/99tc and O/Fujian/CHA/9/99tc) of FMDV serotype O. To identify the molecular determinant(s) for the interaction of O/Tibet/CHA/6/99tc and O/Fujian/CHA/9/99tc with HS receptor, several chimeric viruses and site-directed mutants were generated by using an infectious cDNA of a non-HS-utilizing rescued virus (Cathay topotype) as the genomic backbone. Phenotypic properties of these viruses were determined by plaque assays and virus adsorption and penetration assays in cultured cells. Results: Only two of the rescued viruses encoding VP0 of O/Tibet/CHA/6/99tc or VP1 of O/Fujian/CHA/9/99tc formed plaques on wild-type Chinese hamster ovary (WT-CHO; HS+) cells, but not on HS-negative pgsD-677 cells. The formation of plaques by these two chimeric viruses on WT-CHO cells could be abolished by the introduction of single amino acid mutations Gln-2080 -> Leu in VP2 of O/Tibet/CHA/6/99tc and Lys-1083 -> Glu in VP1 of O/Fujian/CHA/9/99tc, respectively. Nonetheless, the introduced mutation Leu-2080 -> Gln in VP2 of O/Fujian/CHA/9/99tc for the construction of expectant recombinant plasmid led to non-infectious progeny virus in baby hamster kidney 21 (BHK-21) cells, and the site-directed mutant encoding Glu-1083 -> Lys in VP1 of O/Tibet/CHA/6/99tc did not acquire the ability to produce plaques on WT-CHO cells. Significant differences in the inhibition of the infectivity of four HS-utilizing viruses by heparin and RGD-containing peptide were observed in BHK-21 cells. Interestingly, the chimeric virus encoding VP0 of O/Fujian/CHA/9/99tc, and the site-directed mutant encoding Gln-2080 -> Leu in VP2 of O/Tibet/CHA/6/99tc could bind to HS, but there was no expression of the 3A protein of these two viruses in WT-CHO cells. Conclusion: The results suggest that the cooperation of certain specific amino acid residues in the capsid proteins of these two cell-adapted PanAsia-1 strains is essential for viral infectivity, the heparin affinity and the capability on FMDV-HS interaction.

引用

页数：12

共 51 条

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