Structure and Function of the Influenza Virus Transcription and Replication Machinery.

TitleStructure and Function of the Influenza Virus Transcription and Replication Machinery.
Publication TypeJournal Article
Year of Publication2020
AuthorsFodor, E, Velthuis, AJWTe
JournalCold Spring Harb Perspect Med
Volume10
Issue9
Date Published2020/09/01
ISSN2157-1422
KeywordsHost-Pathogen Interactions, Humans, Influenza A virus, Influenza, Human, Nuclear Proteins, RNA, Viral, RNA-Binding Proteins, RNA-Dependent RNA Polymerase, Viral Transcription, Virus Replication
Abstract

Transcription and replication of the influenza virus RNA genome is catalyzed 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 of 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 review discusses recent insights into the structure-function relationship of the viral RNA polymerase and its role in determining host range and virulence.

DOI10.1101/cshperspect.a038398
Alternate JournalCold Spring Harb Perspect Med
PubMed ID31871230
PubMed Central IDPMC7334866
Grant List / WT_ / Wellcome Trust / United Kingdom
MR/R009945/1 / MRC_ / Medical Research Council / United Kingdom
R21 AI147172 / AI / NIAID NIH HHS / United States
206579/Z/17/Z / WT_ / Wellcome Trust / United Kingdom