Zuñiga Sonia, Pascual-Iglesias Alejandro, Sanchez Carlos M, Sola Isabel, Enjuanes Luis
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin 3, Madrid, Spain.
Department of Molecular and Cell Biology, National Center of Biotechnology (CNB-CSIC), Campus Universidad Autónoma de Madrid, Darwin 3, Madrid, Spain.
Virus Res. 2016 Dec 2;226:142-151. doi: 10.1016/j.virusres.2016.07.003. Epub 2016 Jul 7.
Porcine enteric coronaviruses (CoVs) cause severe disease in the porcine herds worldwide, leading to important economic losses. Despite the knowledge of these viruses since the 1970s, vaccination strategies have not been implemented, leading to continuous re-emergence of novel virulent strains. Live attenuated vaccines historically have been the most efficient. We consider that the new trend is the development of recombinant vaccines by using reverse genetics systems to engineer attenuated viruses, which could be used as effective and safe modified live vaccine candidates. To this end, host cell signaling pathways influencing porcine CoV virulence should be identified. Similarly, the identity of viral proteins involved in the modulation of host cell pathways influencing CoV pathogenesis should be analyzed. With this information, and using reverse genetics systems, it is possible to design viruses with modifications in the viral proteins acting as virulence factors, which may lead to attenuated viruses and, therefore, vaccine candidates. In addition, novel antiviral drugs may be developed once the host cell pathways and the molecular mechanism affecting porcine CoV replication and virulence are known. This review is focused in the host cell responses to enteric porcine CoV infection and the viral proteins involved in pathogenesis.
猪肠道冠状病毒（CoVs）在全球猪群中引发严重疾病，导致重大经济损失。尽管自20世纪70年代以来就已了解这些病毒，但尚未实施疫苗接种策略，导致新型强毒株不断重新出现。历史上减毒活疫苗一直是最有效的。我们认为新趋势是利用反向遗传学系统改造减毒病毒来开发重组疫苗，这些减毒病毒可作为有效且安全的新型活疫苗候选物。为此，应确定影响猪CoV毒力的宿主细胞信号通路。同样，应分析参与调节影响CoV发病机制的宿主细胞通路的病毒蛋白的特性。有了这些信息，并利用反向遗传学系统，就有可能设计出在作为毒力因子的病毒蛋白上有修饰的病毒，这可能会产生减毒病毒，进而成为疫苗候选物。此外，一旦了解影响猪CoV复制和毒力的宿主细胞通路及分子机制，就可能开发出新的抗病毒药物。本综述聚焦于宿主细胞对猪肠道CoV感染的反应以及参与发病机制的病毒蛋白。
