Kato A, Kiyotani K, Sakai Y, Yoshida T, Nagai Y
Department of Viral Infection, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
EMBO J. 1997 Feb 3;16(3):578-87. doi: 10.1093/emboj/16.3.578.
The Sendai virus (SeV) V protein is characterized by the unique cysteine-rich domain in its carboxy-terminal half which is fused to the amino-terminal half of the P protein, but its function has remained enigmatic. The V protein-directing mRNA is generated by a remarkable process known as mRNA editing involving the pseudotemplated addition of a single G residue at a specific septinucleotide locus in the P gene, whereas the unedited exact copy encodes the P protein. Here, we introduced two nucleotide changes in the septinucleotide motif (UUUUCCC to UUCUUCC) in a full-length SeV cDNA and were able to recover a virus from the cDNA, which was devoid of mRNA editing and hence unable to synthesize the V protein. Compared with the parental wild-type virus with regard to gene expression, replication and cytopathogenicity in various cell lines in vitro, the V(-) virus was found to be either potentiated or comparable but never attenuated. The V(-) virus, however, showed markedly attenuated in vivo replication capacity in and pathogenicity for mice. Thus, though categorized as a nonessential gene product, SeV V protein encodes a luxury function required for in vivo pathogenicity.
仙台病毒（SeV）的V蛋白在其羧基末端的一半具有独特的富含半胱氨酸的结构域，该结构域与P蛋白的氨基末端一半融合，但其功能一直不明。指导V蛋白合成的mRNA是通过一个称为mRNA编辑的显著过程产生的，该过程涉及在P基因的特定七核苷酸位点以假模板方式添加单个G残基，而未编辑的精确拷贝则编码P蛋白。在此，我们在全长SeV cDNA的七核苷酸基序（UUUUCCC变为UUCUUCC）中引入了两个核苷酸变化，并能够从该cDNA中回收一种病毒，该病毒缺乏mRNA编辑，因此无法合成V蛋白。与亲代野生型病毒相比，在体外各种细胞系中的基因表达、复制和细胞致病性方面，V（-）病毒被发现要么增强，要么相当，但从未减弱。然而，V（-）病毒在小鼠体内的复制能力和致病性明显减弱。因此，尽管SeV V蛋白被归类为非必需基因产物，但它编码了体内致病性所需的一种奢侈功能。
