期刊
JOURNAL OF GENERAL VIROLOGY
卷 97, 期 -, 页码 2494-2500出版社
MICROBIOLOGY SOC
DOI: 10.1099/jgv.0.000564
关键词
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资金
- Deutsche Forschungsgemeinschaft, DFG [Sonderforschungsbereich SFB1021]
- Leibniz-Gemeinschaft through the EIDIS graduate school
Marburg virus (MARV) causes severe, often fatal, disease in humans and transient illness in rodents. Sequential passaging of MARV in guinea pigs resulted in selection of a lethal virus containing 4 aa changes. A D184N mutation in VP40 (VP40(D184N)), which leads to a species-specific gain of viral fitness, and three mutations in the active site of viral RNA-dependent RNA polymerase L, which were investigated in the present study for functional significance in human and guinea pig cells. The transcription/replication activity of L mutants was strongly enhanced by a substitution at position 741 (S741C), and inhibited by other substitutions (D758A and A759D) in both species. The polymerase activity of L carrying the S741C substitution was eightfold higher in guinea pig cells than in human cells upon co-expression with VP40(D184N), suggesting that the additive effect of the two mutations provides MARV a replicative advantage in the new host.
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