title: An active site mutation increases the polymerase activity of the guinea pig-lethal Marburg virus.
abstract: 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.
authors.affiliation: Institut für Virologie, Philipps-Universität Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Koehler
authors.affiliation: Institut für Virologie, Philipps-Universität Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kolesnikova
authors.affiliation: German Center for Infection Research (DZIF), Institut für Virologie, Philipps-Universität, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.|Institut für Virologie, Philipps-Universität Marburg, Hans-Meerwein-Str. 2, 35043 Marburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Becker
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006168:Guinea Pigs / Q000821:virology*; D008379:Marburg Virus Disease / Q000401:mortality / Q000821:virology*; D029024:Marburgvirus / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D020125:Mutation, Missense; D012376:Rodent Diseases / Q000401:mortality / Q000821:virology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases