Accumulation of infectious mutants in stocks during the propagation of fiber-modified recombinant adenoviruses
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- 作者：Hideyo Ugai ; Kumiko Inabe ; Takahito Yamasaki ; Takehide Murata ; Yuichi Obata ; Hirofumi Hamada and Kazunari K. Yokoyama
- 关键词：Recombinant adenovirus ; Fiber modification ; Spontaneous mutation ; Viral instability ; Safety
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2005
- 出版时间：2005
- 年：2005
- 卷：337
- 期：3
- 页码：806-814
- 全文大小：411 K
文摘
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.