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Structure and function of the influenza virus transcription and replication machinery

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Fodor, Ervin 


Transcription and replication of the influenza virus RNA genome is catalysed by the viral heterotrimeric RNA-dependent RNA polymerase in the context of viral ribonucleoprotein (vRNP) complexes. Atomic resolution structures of the viral RNA synthesis machinery have offered insights into the initiation mechanisms of viral transcription and genome replication, and the interaction of the viral RNA polymerase with host RNA polymerase II, which is required for the initiation of viral transcription. Replication of the viral RNA genome by the viral RNA polymerase depends on host ANP32A, and host-specific sequence differences in ANP32A underlie the poor activity of avian influenza virus polymerases in mammalian cells. A failure to faithfully copy the viral genome segments can lead to the production aberrant viral RNA products, such as defective interfering (DI) RNAs and mini viral RNAs (mvRNAs). Both aberrant RNA types have been implicated in innate immune responses against influenza virus infection. This chapter discusses recent insights into the structure-function relationship of the viral RNA polymerase and its role in determining host range and virulence.



Host-Pathogen Interactions, Humans, Influenza A virus, Influenza, Human, Nuclear Proteins, RNA, Viral, RNA-Binding Proteins, RNA-Dependent RNA Polymerase, Viral Transcription, Virus Replication

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Cold Spring Harbor Perspectives in Medicine

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Cold Spring Harbor Laboratory Press


All rights reserved
Wellcome Trust (206579/Z/17/Z)
Isaac Newton Trust (17.37 (r))
National Institutes of Health (NIH) (1R21AI147172-01)
E. Fodor is supported by UK Medical Research Council programme grant MR/R009945/1. A. te Velthuis is supported by joint Wellcome Trust and Royal Society grant 206579/Z/17/Z, Isaac Newton Trust grant 17.37(r), and the National Institutes of Health grant R21AI147172.