The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes.
The role of accessory proteins in the replication of feline infectious peritonitis virus in peripheral blood monocytes.
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DOI：
10.1016/j.vetmic.2012.10.032
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发表时间：
2013-03-23
影响因子：
3.3
通讯作者：
Nauwynck HJ
中科院分区：
文献类型：
--
作者：
Dedeurwaerder A;Desmarets LM;Olyslaegers DAJ;Vermeulen BL;Dewerchin HL;Nauwynck HJ
低毒力猫科肠道冠状病毒(FECV)与致死性猫科动物感染性腹膜炎病毒(FIPV)最重要的区别是感染单核/巨噬细胞的能力。在体外，FECV在外周血单核细胞中的复制在接种后12h后一直下降，而FIPV在45%的猫的单核细胞中的复制保持不变。猫冠状病毒的辅助蛋白被推测在毒力中起着重要作用，因为缺失被发现与减毒病毒有关。尽管如此，它们还没有被赋予任何功能。为了研究FIPV79-1146及其缺失突变体的复制动力学，我们测定了FIPV79-1146及其缺失突变体的复制动力学，这些突变体既缺少辅助蛋白开放阅读框3abc(FIPV-Δ3)、7AB(FIPV-Δ7)，又缺失两者(FIPV-Δ3Δ7)。结果表明，缺失突变体FIPV-Δ7和FIPV-Δ3Δ7不能维持其复制，这与wt-FIPV形成鲜明对比。FIPV-Δ-3仍能维持其复制，但感染的单核细胞比例始终低于wt-FIPV。综上所述，本研究表明ORF7对FIPV在单核/巨噬细胞中的复制至关重要，并对其在体内的重要性、在FIP的发生发展中的作用以及在野毒株中的保守性进行了解释。ORF3缺失的影响不那么明显，这表明在FIPV感染体内靶细胞的过程中，ORF3编码的蛋白只起到了辅助作用。
The ability to productively infect monocytes/macrophages is the most important difference between the low virulent feline enteric coronavirus (FECV) and the lethal feline infectious peritonitis virus (FIPV). In vitro, the replication of FECV in peripheral blood monocytes always drops after 12 h post inoculation, while FIPV sustains its replication in the monocytes from 45% of the cats. The accessory proteins of feline coronaviruses have been speculated to play a prominent role in virulence as deletions were found to be associated with attenuated viruses. Still, no functions have been ascribed to them. In order to investigate if the accessory proteins of FIPV are important for sustaining its replication in monocytes, replication kinetics were determined for FIPV 79-1146 and its deletion mutants, lacking either accessory protein open reading frame 3abc (FIPV-Δ3), 7ab (FIPV-Δ7) or both (FIPV-Δ3Δ7). Results showed that the deletion mutants FIPV-Δ7 and FIPV-Δ3Δ7 could not maintain their replication, which was in sharp contrast to wt-FIPV. FIPV-Δ3 could still sustain its replication, but the percentage of infected monocytes was always lower compared to wt-FIPV. In conclusion, this study showed that ORF7 is crucial for FIPV replication in monocytes/macrophages, giving an explanation for its importance in vivo, its role in the development of FIP and its conservation in field strains. The effect of an ORF3 deletion was less pronounced, indicating only a supportive role of ORF3 encoded proteins during the infection of the in vivo target cell by FIPVs.
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影响因子：
1
作者：
Kennedy, Melissa A.;Abd-Eldaim, Mohamed;Kania, Stephen A.
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