Cyclin T1/CDK9 interacts with influenza A virus polymerase and facilitates its association with cellular RNA polymerase II

Junjie Zhang; Gang Li; Xin Ye

doi:10.1128/JVI.01696-10

Cyclin T1/CDK9 interacts with influenza A virus polymerase and facilitates its association with cellular RNA polymerase II

J Virol. 2010 Dec;84(24):12619-27. doi: 10.1128/JVI.01696-10. Epub 2010 Oct 13.

Authors

Junjie Zhang¹, Gang Li, Xin Ye

Affiliation

¹ Center for Molecular Immunology, Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, CAS, 1 Beichen West Road, Chaoyang District, Beijing 100101, People's Republic of China.

Abstract

Influenza virus RNA-dependent RNA polymerase scavenges the 5' cap from host pre-mRNA to prime viral transcription initiation. It is also well established that viral RNA-dependent RNA polymerase (vRNP) associates with cellular RNA polymerase II (Pol II), on which viral replication depends. Here we report that cyclin T1/CDK9 can interact with influenza virus polymerase and facilitate its association with cellular Pol II. The immunodepletion of cyclin T1/CDK9 totally abolished the association of vRNP with the C-terminal domain (CTD) Ser-2-phosphorylated form of RNA polymerase II. Further studies showed that overexpression of cyclin T1/CDK9 increased the transcription activity of vRNP, while knockdown of cyclin T1/CDK9 impaired viral replication. Our results suggest that cyclin T1/CDK9 serves as an adapter to mediate the interaction of vRNP and RNA Pol II and promote viral transcription.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blotting, Western
Cells, Cultured
Cyclin T / antagonists & inhibitors
Cyclin T / genetics
Cyclin T / metabolism*
Cyclin-Dependent Kinase 9 / antagonists & inhibitors
Cyclin-Dependent Kinase 9 / genetics
Cyclin-Dependent Kinase 9 / metabolism*
Dogs
Fluorescent Antibody Technique
Humans
Immunoprecipitation
Influenza A virus / enzymology*
Influenza, Human / enzymology
Influenza, Human / genetics
Influenza, Human / virology
Kidney / cytology
Kidney / metabolism
Kidney / virology
Orthomyxoviridae Infections / enzymology
Orthomyxoviridae Infections / genetics
Orthomyxoviridae Infections / virology
RNA Polymerase II / genetics
RNA Polymerase II / metabolism*
RNA Precursors / genetics
RNA, Messenger / genetics
RNA, Small Interfering / pharmacology
RNA-Dependent RNA Polymerase / genetics
RNA-Dependent RNA Polymerase / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transcription, Genetic
Virus Replication / genetics*

Substances

Cyclin T
RNA Precursors
RNA, Messenger
RNA, Small Interfering
Cyclin-Dependent Kinase 9
RNA Polymerase II
RNA-Dependent RNA Polymerase