Different domains of the RNA polymerase of infectious bursal disease virus contribute to virulence.
Different domains of the RNA polymerase of infectious bursal disease virus contribute to virulence.
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DOI：
10.1371/journal.pone.0028064
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Eterradossi N
中科院分区：
文献类型：
--
作者：
Nouën CL;Toquin D;Müller H;Raue R;Kean KM;Langlois P;Cherbonnel M;Eterradossi N
传染性法氏囊病病毒(IBDV)是一种对养禽业具有世界性意义的病原体。IBDV基因组为双节段双链RNA。A节段和B节段分别编码衣壳、核糖核蛋白和非结构蛋白，或病毒聚合酶(RdRp)。自80年代末以来，欧洲出现了毒力极强的(Vv)IBDV毒株，导致高达60%的死亡。虽然对IBDV的分子生物学研究已经取得了一些进展，但vvIBDV致病的分子基础仍不完全清楚。88180株属于与vvIBDV有亲缘关系的致病IBDV谱系。通过反向遗传学方法，我们挽救了一个与其亲本菌株致病性相同的分子克隆(Mc88180)。为了研究88180致病的分子基础，我们构建并鉴定了来源于88180株和减毒株的重组或镶嵌重组病毒。从88180的A节段(A88)和B节段(BCU1)中救出的重配病毒比MC88180弱，表明B节段参与了88180的致病过程。接下来，BCU1的不同区域与B88中的对应区域与A88相关的不同区域的交换并未完全恢复相当于MC88180的毒力。这表明，B88的几个区域，如果不是整个B88，对于88180的体内致病性是必不可少的。目前的结果表明，RdRp的不同结构域对IBDV的体内致病性是必不可少的，与花叶病毒的复制效率无关。
Infectious bursal disease virus (IBDV) is a pathogen of worldwide significance to the poultry industry. IBDV has a bi-segmented double-stranded RNA genome. Segments A and B encode the capsid, ribonucleoprotein and non-structural proteins, or the virus polymerase (RdRp), respectively. Since the late eighties, very virulent (vv) IBDV strains have emerged in Europe inducing up to 60% mortality. Although some progress has been made in understanding the molecular biology of IBDV, the molecular basis for the pathogenicity of vvIBDV is still not fully understood. Strain 88180 belongs to a lineage of pathogenic IBDV phylogenetically related to vvIBDV. By reverse genetics, we rescued a molecular clone (mc88180), as pathogenic as its parent strain. To study the molecular basis for 88180 pathogenicity, we constructed and characterized in vivo reassortant or mosaic recombinant viruses derived from the 88180 and the attenuated Cu-1 IBDV strains. The reassortant virus rescued from segments A of 88180 (A88) and B of Cu-1 (BCU1) was milder than mc88180 showing that segment B is involved in 88180 pathogenicity. Next, the exchange of different regions of BCU1 with their counterparts in B88 in association with A88 did not fully restore a virulence equivalent to mc88180. This demonstrated that several regions if not the whole B88 are essential for the in vivo pathogenicity of 88180. The present results show that different domains of the RdRp, are essential for the in vivo pathogenicity of IBDV, independently of the replication efficiency of the mosaic viruses.
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