Accumulation of infectious mutants in stocks during the propagation of fiber-modified recombinant adenoviruses.
In infected cells, replication errors during viral proliferation generate mutations in adenoviruses (Ads), and the mutant Ads proliferate and evolve in the intracellular environment. Genetically fiber-modified recombinant Ads (rAd variants) were generated, by modification of the fiber gene, for therapeutic applications in host cells that lack or express reduced levels of the Coxsackievirus and adenovirus receptor. To assess the genetic modifications of rAd variants that might induce the instability of Ad virions, we examined the frequencies of mutants that accumulated in propagated stocks. Seven of 41 lines of Ad variants generated mutants in the stocks and all mutants were infectious. Moreover, all the mutations occurred in the modified region that had been added at the 3' end of the fiber gene. Our results show that some genetic modifications at the carboxyl terminus of Ad fiber protein lead to the instability of Ad virions.
Ugai
Hideyo
H
Gene Engineering Division, Department of Biological Systems, BioResource Center, Tsukuba Institute, RIKEN The Institute of Physical and Chemical Research, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan.
Inabe
Kumiko
K
Yamasaki
Takahito
T
Murata
Takehide
T
Obata
Yuichi
Y
Hamada
Hirofumi
H
Yokoyama
Kazunari K
KK
D000256:Adenoviridae / Q000235:genetics* / Q000254:growth & development* / Q000302:isolation & purification / Q000472:pathogenicity; D000595:Amino Acid Sequence; D001483:Base Sequence; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics*; D002460:Cell Line; D004252:DNA Mutational Analysis; D014644:Genetic Variation / Q000235:genetics; D005822:Genetic Vectors; D016679:Genome, Viral; D006801:Humans; D007668:Kidney / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D011995:Recombination, Genetic / Q000235:genetics; D014162:Transfection / Q000379:methods*; D014779:Virus Replication / Q000235:genetics*
D036022:Capsid Proteins