Tal Saar, Mincberg Michal, Rostovsky Irina, Rommelaere Jean, Salome Nathali, Davis Claytus
Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Division ofTumor Virology, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Virology. 2014 Nov;468-470:631-636. doi: 10.1016/j.virol.2014.08.032. Epub 2014 Oct 11.
The P4 promoter of the autonomous parvovirus Minute Virus of Mice (MVM) drives the production of its non-structural proteins, NS1 and NS2. The NS2 isoforms are without enzymatic activity but interact with cellular proteins. While NS2 is crucial to the viral life cycle in cultured murine cells, NS2-null mutant virus productively infects transformed host cells of other species. In the mouse, sensitivity to MVM infection is age dependent, exhibiting limited subclinical infections in adults, but sustained and potentially lethal infection in embryos. We therefore questioned whether the species-dependent requirement for NS2 function in vitro would be retained in utero. We report here that it is not. NS2-null mutant MVMp is capable of mounting a productive, albeit much reduced, infection of normal embryonic mouse cells in vivo. Based on the data, we hypothesize that NS2 may bear an as-yet undescribed immunosuppressive function.
自主细小病毒小鼠微小病毒(MVM)的P4启动子驱动其非结构蛋白NS1和NS2的产生。NS2亚型没有酶活性,但能与细胞蛋白相互作用。虽然NS2对培养的鼠细胞中的病毒生命周期至关重要,但缺失NS2的突变病毒能有效感染其他物种的转化宿主细胞。在小鼠中,对MVM感染的敏感性取决于年龄,在成年小鼠中表现为有限的亚临床感染,但在胚胎中则是持续且可能致命的感染。因此,我们质疑NS2功能在体外对物种的依赖性需求在子宫内是否仍然存在。我们在此报告并非如此。缺失NS2的突变型MVMp能够在体内对正常胚胎小鼠细胞进行有效感染,尽管感染程度大大降低。基于这些数据,我们推测NS2可能具有一种尚未被描述的免疫抑制功能。