Identification of an NTPase motif in classical swine fever virus NS4B protein
Identification of an NTPase motif in classical swine fever virus NS4B protein
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DOI：
10.1016/j.virol.2010.12.028
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发表时间：
2011-03-01
期刊：
影响因子：
3.7
通讯作者：
Borca, Manuel V.
中科院分区：
文献类型：
--
作者：
Gladue, Douglas P.;Gavrilov, Boris K.;Borca, Manuel V.
猪瘟（CSF）是由猪瘟病毒（CSF virus， CSFV）引起的一种高度传染性且往往致命的猪疾病，猪瘟病毒是黄病毒科鼠疫病毒属的一种阳性单链RNA病毒。在这里，我们已经确定了在猪瘟非结构（NS）蛋白NS4B中水解ntp的核苷酸结合基序（NBM）中观察到的保守序列元件。表达的NS4B蛋白水解ATP和GTP。在鉴定的NS4B NBM Walker A和B基序内的关键残基的替换显著损害了表达蛋白的atp酶和GTPase活性。在CSFV布雷西亚菌株全长cDNA拷贝的遗传主干中引入类似的突变，不会产生传染性病毒或复制能力受损的病毒，这表明该NTPase活性对CSFV周期至关重要。恢复的突变病毒在感染猪中保留了毒力表型，如亲本布雷西亚病毒株。这些结果对开发针对猪瘟病毒感染的新型抗病毒策略具有重要意义。Elsevier Inc.出版。
Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive-sense single-stranded RNA virus within the Pestivirus genus of the Flaviviridae family. Here, we have identified conserved sequence elements observed in nucleotide-binding motifs (NBM) that hydrolyze NTPs within the CSFV non-structural (NS) protein NS4B. Expressed NS4B protein hydrolyzes both ATP and GTP. Substitutions of critical residues within the identified NS4B NBM Walker A and B motifs significantly impair the ATPase and GTPase activities of expressed proteins. Similar mutations introduced into the genetic backbone of a full-length cDNA copy of CSFV strain Brescia rendered no infectious viruses or viruses with impaired replication capabilities, suggesting that this NTPase activity is critical for the CSFV cycle. Recovered mutant viruses retained a virulent phenotype, as parental strain Brescia, in infected swine. These results have important implications for developing novel antiviral strategies against CSFV infection. Published by Elsevier Inc.