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De Novo Replication of the Influenza Virus RNA Genome is Regulated by DNA Replicative Helicase, MCM

Overview
Journal EMBO J
Date 2007 Oct 13
PMID 17932485
Citations 57
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Abstract

By dissecting and reconstituting a cell-free influenza virus genome replication system, we have purified and identified the minichromosome maintenance (MCM) complex, which is thought to be a DNA replicative helicase, as one of the host factors that regulate the virus genome replication. MCM interacted with the PA subunit of the viral RNA-dependent RNA polymerase that is found to be involved in the replication genetically. The virus genome replication was decreased in MCM2 knockdown cells. The viral polymerase appeared to be a nonproductive complex, that is, it was capable of initiating replication but produced only abortive short RNA chains. MCM stimulated de novo-initiated replication reaction by stabilizing a replication complex during its transition from initiation to elongation. Based on the findings, including the result that the MCM-mediated RNA replication reaction was competed with exogenously added RNA, we propose that MCM functions as a scaffold between the nascent RNA chains and the viral polymerase.

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References
1.
Huarte M, Sanz-Ezquerro J, Roncal F, Ortin J, Nieto A . PA subunit from influenza virus polymerase complex interacts with a cellular protein with homology to a family of transcriptional activators. J Virol. 2001; 75(18):8597-604. PMC: 115105. DOI: 10.1128/jvi.75.18.8597-8604.2001. View

2.
Honda A, Mizumoto K, Ishihama A . RNA polymerase of influenza virus. Dinucleotide-primed initiation of transcription at specific positions on viral RNA. J Biol Chem. 1986; 261(13):5987-91. View

3.
Ishimi Y, Okayasu I, Kato C, Kwon H, Kimura H, Yamada K . Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix. Eur J Biochem. 2003; 270(6):1089-101. DOI: 10.1046/j.1432-1033.2003.03440.x. View

4.
Chan A, Vreede F, Smith M, Engelhardt O, Fodor E . Influenza virus inhibits RNA polymerase II elongation. Virology. 2006; 351(1):210-7. DOI: 10.1016/j.virol.2006.03.005. View

5.
Gabriel G, Abram M, Keiner B, Wagner R, Klenk H, Stech J . Differential polymerase activity in avian and mammalian cells determines host range of influenza virus. J Virol. 2007; 81(17):9601-4. PMC: 1951401. DOI: 10.1128/JVI.00666-07. View