The paramyxovirus, Sendai virus, V protein encodes a luxury function required for viral pathogenesis.
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.
Kato
A
A
Department of Viral Infection, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Kiyotani
K
K
Sakai
Y
Y
Yoshida
T
T
Nagai
Y
Y
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000821:virology; D051379:Mice; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins; D010957:Plasmids / Q000235:genetics; D017393:RNA Editing / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018108:Respirovirus / Q000737:chemistry*; D010253:Respirovirus Infections / Q000821:virology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; C055859:P protein, Sendai virus; D010750:Phosphoproteins; D012333:RNA, Messenger; D014764:Viral Proteins; C074576:V protein, Porcine rubulavirus