%0 Journal Article %A Koehler, Alexander %A Kolesnikova, Larissa %A Becker, Stephan %T An active site mutation increases the polymerase activity of the guinea pig-lethal Marburg virus %D 2016 %J Journal of General Virology, %V 97 %N 10 %P 2494-2500 %@ 1465-2099 %R https://doi.org/10.1099/jgv.0.000564 %K transcription %K Marburg virus %K RNA-dependent RNA polymerase %K replication %K viral polymerase L %I Microbiology Society, %X 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 (VP40D184N), 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 VP40D184N, suggesting that the additive effect of the two mutations provides MARV a replicative advantage in the new host. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000564