Abstract:
:Passage of foot-and-mouth disease virus (FMDV) in cell culture in the presence of the mutagenic base analog 5-fluorouracil or 5-azacytidine resulted in decreases of infectivity and occasional extinction of the virus. Low viral loads and low viral fitness enhanced the frequency of extinction events; this finding was shown with a number of closely related FMDV clones and populations differing by up to 10(6)-fold in relative fitness in infections involving either single or multiple passages in the absence or presence of the chemical mutagens. The mutagenic treatments resulted in increases of 2- to 6.4-fold in mutation frequency and up to 3-fold in mutant spectrum complexity. The largest increase observed corresponded to the 3D (polymerase)-coding region, which is highly conserved in nonmutagenized FMDV populations. As a result, nucleotide sequence heterogeneity for the 3D-coding region became very similar to that for the variable VP1-coding region in FMDVs multiply passaged in the presence of chemical mutagens. The results suggest that strategies to combine reductions of viral load and viral fitness could be effectively associated with extinction mutagenesis as a potential new antiviral strategy.
journal_name
J Viroljournal_title
Journal of virologyauthors
Sierra S,Dávila M,Lowenstein PR,Domingo Edoi
10.1128/jvi.74.18.8316-8323.2000subject
Has Abstractpub_date
2000-09-01 00:00:00pages
8316-23issue
18eissn
0022-538Xissn
1098-5514journal_volume
74pub_type
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2012-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/jvi.78.5.2454-2459.2004
更新日期:2004-03-01 00:00:00
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journal_title:Journal of virology
pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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