Mutations affecting transcriptional termination in the p gene end of subacute sclerosing panencephalitis viruses.
Numerous mutations are found in subacute sclerosing panencephalitis (SSPE) viruses, and the M gene is the gene most commonly affected. In some SSPE viruses, such as the MF, Osaka-1, Osaka-2, and Yamagata-1 strains, translation of the M protein is complicated by a transcriptional defect that leads to an almost exclusive synthesis of dicistronic P-M mRNA. To understand the molecular mechanisms of this defect, we sequenced the P gene at the P-M gene junction for several virus strains and probed the involvement of several mutations in the readthrough region via their expression in measles virus minigenomes containing different sequences of the P-M gene junction and flanking reporter genes. The deletion of a single U residue in the U tract of the Osaka-1 strain (3'-UAAUAUUUUU-5') compared with the consensus sequence resulted in a marked reduction of the expression of the downstream reporter gene. In addition, the expression of the downstream gene was markedly decreased by (i) the substitution of a C residue in the U tract of the P gene end of the OSA-2/Fr/B strain of the Osaka-2 virus (3'-UGAUAUUCUU-5' compared with the sequence 3'-UGAUAUUUUU-5' from a sibling virus of the same strain, OSA-2/Fr/V), and (ii) the substitution of a G in the sequence of the P gene end of the Yamagata-1 strain at a variable site immediately upstream from the six-U tract (3'-UGAUGUUUUUU-5' instead of 3'-UGAUUUUUUUU-5'). Mutations at the P gene end can account for the readthrough transcription variation at the P-M gene junction, which directly affects M protein expression.
Ayata
Minoru
M
Department of Virology, Osaka City University Medical School, Asahimachi, Abeno-ku, Osaka 545-8585, Japan. maverick@med.osaka-cu.ac.jp
Komase
Katsuhiro
K
Shingai
Masashi
M
Matsunaga
Isamu
I
Katayama
Yuko
Y
Ogura
Hisashi
H
D001483:Base Sequence; D005814:Genes, Viral; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics*; D013190:SSPE Virus / Q000235:genetics*; D014158:Transcription, Genetic; D014763:Viral Matrix Proteins / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics*
D010750:Phosphoproteins; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins