Versatility of the accessory C proteins of Sendai virus: contribution to virus assembly as an additional role.
The P/C mRNA of Sendai virus (SeV) encodes a nested set of accessory proteins, C', C, Y1, and Y2, referred to collectively as C proteins, using the +1 frame relative to the open reading frame of phospho (P) protein and initiation codons at different positions. The C proteins appear to be basically nonstructural proteins as they are found abundantly in infected cells but greatly underrepresented in the virions. We previously created a 4C(-) SeV, which expresses none of the four C proteins, and concluded that the C proteins are categorically nonessential gene products but greatly contribute to viral full replication and infectivity (A. Kurotani et al., Genes Cells 3:111-124, 1998). Here, we further characterized the 4C(-) virus multiplication in cultured cells. The viral protein and mRNA synthesis was enhanced with the mutant virus relative to the parental wild-type (WT) SeV. However, the viral yields were greatly reduced. In addition, the 4C(-) virions appeared to be highly anomalous in size, shape, and sedimentation profile in a sucrose gradient and exhibited the ratios of infectivity to hemagglutination units significantly lower than those of the WT. In the WT infected cells, C proteins appeared to colocalize almost perfectly with the matrix (M) proteins, pretty well with an external envelope glycoprotein (hemagglutinin-neuraminidase [HN]), and very poorly with the internal P protein. In the absence of C proteins, there was a significant delay of the incorporation of M protein and both of the envelope proteins, HN and fusion (F) proteins, into progeny virions. These results strongly suggest that the accessory and basically nonstructural C proteins are critically required in the SeV assembly process. This role of C proteins was further found to be independent of their recently discovered function to counteract the antiviral action of interferon-alpha/beta. SeV C proteins thus appear to be quite versatile.
Hasan
M K
MK
Department of Viral Diseases and Vaccine Control, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Kato
A
A
Muranaka
M
M
Yamaguchi
R
R
Sakai
Y
Y
Hatano
I
I
Tashiro
M
M
Nagai
Y
Y
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D002522:Chlorocebus aethiops; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D015707:HN Protein / Q000096:biosynthesis / Q000378:metabolism; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D016253:Microscopy, Immunoelectron; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics; D018108:Respirovirus / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000378:metabolism; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D015707:HN Protein; D016898:Interferon-alpha; C097020:M protein, Sendai virus; C055859:P protein, Sendai virus; D010750:Phosphoproteins; D012367:RNA, Viral; D014760:Viral Fusion Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C051221:nonstructural C protein, Sendai virus; D016899:Interferon-beta