TY - JOUR
T1 - Biased hypermutation and other genetic changes in defective measles viruses in human brain infections
AU - Cattaneo, Roberto
AU - Schmid, Anita
AU - Eschle, Daniel
AU - Baczko, Knut
AU - ter Meulen, Volker
AU - Billeter, Martin A.
N1 - Funding Information:
We thank Charles Weissmann for helpful discussions, Bert Rima for communicating unpublished data, lsidro Ballart for part of the M gene sequence of case MF, Hugh Pelham, Pramod Yadava, and Deborah Maguire for critical comments on the manuscript, and Fritz Ochsen-bein for the photographs. This work was supported by grant 3.141-085 of the Schweizerische Nationalfonds, by the Kanton Ziirich, and by the Deutsche Forschungsgemeinschaft.
PY - 1988/10/21
Y1 - 1988/10/21
N2 - We assessed the alterations of viral gene expression occurring during persistent infections by cloning full-length transcripts of measles virus (MV) genes from brain autopsies of two subacute sclerosing panencephalitis patients and one measles inclusion body encephalitis (MIBE) patient. The suquence of these MV genes revealed that, most likely, almost 2% of the nucleotides were mutated during persistence, and 35% of these differences resulted in amino acid changes. One of these nucleotide substitutions and one deletion resulted in alteration of the reading frames of two fusion genes, as confirmed by in vitro translation of synthetic mRNAs. One cluster of mutations was exceptional; in the matrix gene of the MIBE case, 50% of the U residues were changed to C, which might result from a highly biased copying event exclusively affecting this gene. We propose that the cluster of mutations in the MIBE case, and other combinations of mutations in other cases, favored propagation of MV infections in brain cells by conferring a selective advantage to the mutated genomes.
AB - We assessed the alterations of viral gene expression occurring during persistent infections by cloning full-length transcripts of measles virus (MV) genes from brain autopsies of two subacute sclerosing panencephalitis patients and one measles inclusion body encephalitis (MIBE) patient. The suquence of these MV genes revealed that, most likely, almost 2% of the nucleotides were mutated during persistence, and 35% of these differences resulted in amino acid changes. One of these nucleotide substitutions and one deletion resulted in alteration of the reading frames of two fusion genes, as confirmed by in vitro translation of synthetic mRNAs. One cluster of mutations was exceptional; in the matrix gene of the MIBE case, 50% of the U residues were changed to C, which might result from a highly biased copying event exclusively affecting this gene. We propose that the cluster of mutations in the MIBE case, and other combinations of mutations in other cases, favored propagation of MV infections in brain cells by conferring a selective advantage to the mutated genomes.
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U2 - 10.1016/0092-8674(88)90048-7
DO - 10.1016/0092-8674(88)90048-7
M3 - Article
C2 - 3167982
AN - SCOPUS:0023763122
SN - 0092-8674
VL - 55
SP - 255
EP - 265
JO - Cell
JF - Cell
IS - 2
ER -