EMAIL THIS PAGE TO A FRIEND

Journal of virology

Interactions between the influenza A virus RNA polymerase components and retinoic acid-inducible gene I.


PMID 24942585

Abstract

The influenza A virus genome possesses eight negative-strand RNA segments in the form of viral ribonucleoprotein particles (vRNPs) in association with the three viral RNA polymerase subunits (PB2, PB1, and PA) and the nucleoprotein (NP). Through interactions with multiple host factors, the RNP subunits play vital roles in replication, host adaptation, interspecies transmission, and pathogenicity. In order to gain insight into the potential roles of RNP subunits in the modulation of the host's innate immune response, the interactions of each RNP subunit with retinoic acid-inducible gene I protein (RIG-I) from mammalian and avian species were investigated. Studies using coimmunoprecipitation (co-IP), bimolecular fluorescence complementation (BiFc), and colocalization using confocal microscopy provided direct evidence for the RNA-independent binding of PB2, PB1, and PA with RIG-I from various hosts (human, swine, mouse, and duck). In contrast, the binding of NP with RIG-I was found to be RNA dependent. Expression of the viral NS1 protein, which interacts with RIG-I, did not interfere with the association of RNA polymerase subunits with RIG-I. The association of each individual virus polymerase component with RIG-I failed to significantly affect the interferon (IFN) induction elicited by RIG-I and 5' triphosphate (5'ppp) RNA in reporter assays, quantitative reverse transcription-PCR (RT-PCR), and IRF3 phosphorylation tests. Taken together, these findings indicate that viral RNA polymerase components PB2, PB1, and PA directly target RIG-I, but the exact biological significance of these interactions in the replication and pathogenicity of influenza A virus needs to be further clarified. RIG-I is an important RNA sensor to elicit the innate immune response in mammals and some bird species (such as duck) upon influenza A virus infection. Although the 5'-triphosphate double-stranded RNA (dsRNA) panhandle structure at the end of viral genome RNA is responsible for the binding and subsequent activation of RIG-I, this structure is supposedly wrapped by RNA polymerase complex (PB2, PB1, and PA), which may interfere with the induction of RIG-I signaling pathway. In the present study, PB2, PB1, and PA were found to individually interact with RIG-Is from multiple mammalian and avian species in an RNA-independent manner, without significantly affecting the generation of IFN. The data suggest that although RIG-I binding by RNA polymerase complex is conserved in different species, it does not appear to play crucial role in the modulation of IFN in vitro.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

A8273 Anti-α-Amylase antibody produced in rabbit, fractionated antiserum, lyophilized powder
SAB1410556
Anti-AMY2A antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
HPA039928
Anti-BLOC1S6 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2104315
Anti-DDX58 antibody produced in rabbit, affinity isolated antibody
AV33799
Anti-EPB42 antibody produced in rabbit, affinity isolated antibody
HPA040261
Anti-EPB42 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1407117
Anti-KLK8 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2101826
Anti-PLDN antibody produced in rabbit, affinity isolated antibody
SAB2105000
Anti-PLDN, (N-terminal) antibody produced in rabbit, affinity isolated antibody
PRS3953
Anti-RIG-1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB1300231
Anti-RIG-I (center) antibody produced in rabbit, saturated ammonium sulfate (SAS) precipitated, buffered aqueous solution
SAB1305862
ANTI-RIG-I (CENTER) antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
WH0011202M1
Monoclonal Anti-KLK8 antibody produced in mouse, clone 2F11, purified immunoglobulin, buffered aqueous solution