Pathways:
RIG-I/MAVS/IFNAR1 pathway
Host Molecules Involved:
Eight “suppressor of cytokine signaling” (SOCS) regulatory proteins
Influenza Strain:
Influenza A virus (IAV)
Tissues:
Human respiratory epithelial cells
Interactions:
SOCS1 and SOCS3, RIG-I/MAVS/IFNAR1 pathway
Mechanisms:
- SOCS1 to SOCS7 are constitutively expressed in IAV-infected cells.
- SOCS1 and SOCS3 expressions are up-regulated after IAV infection.
- SOCS1 and SOCS3 up-regulation needs a TLR3-independent, retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling protein (MAVS)/IFNalphabeta receptor (IFNAR)1-dependent pathway.
- SOCS1 and SOCS3 inhibit antiviral responses, and differentially regulate inflammatory signaling pathways.
- MAVS is a RIG-I signaling intermediate.
Effects:
Innate immune response to influenza A virus infection is inhibited by SOCS1 and SOCS3 via the RIG-I/MAVS/IFNAR1-dependent pathway.
Reference:
Pothlichet, J., Chignard, M., et al. (2008) Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway. J Immunol 180, 2034-2038.
Pathways:
Jak/Stat pathway
Host Molecules Involved:
interferons (IFN), in innate immunity
Influenza Strain:
A/Aichi/2/68 (H3N2) (Aichi)
Tissues:
Respiratory epithelial cells
Interactions:
Influenza virus inhibits IFN-gamma.
Mechanisms:
- Influenza infection suppressed IFN-gamma-caused up-regulation of HLA-DRalpha mRNA, and class II transactivator (CIITA), a mediator of MHC class II expression.
- Nuclear translocation of Stat1alpha by IFN-gamma stimulation was suppressed, related to a reduction in Tyr701 and Ser727 phosphorylation of Stat1alpha.
Effects:
Influenza A virus subverts antiviral host defense mediated by IFN-gamma through affecting the intracellular signaling Jak/Stat pathways.
Reference:
Uetani, K., Hiroi, M., et al. (2008) Influenza A virus abrogates IFN-gamma response in respiratory epithelial cells by disruption of the Jak/Stat pathway. Eur J Immunol 38, 1559-1573.
Pathways:
PI3K/Akt signaling pathway
Host Molecules Involved:
Phosphatidylinositol-3-kinase (PI3K), the downstream effector protein kinase Akt
Viral Molecules Involved:
NS1
Tissues:
Influenza A virus-infected cells
Interactions:
PI3K is activated through direct interaction with A/NS1, via the p85 regulatory subunit.
Mechanisms:
- PI3K/Akt signaling is required for functions during infection.
- The kinase activates the interferon regulatory factor-3 during antiviral interferon induction, with virus supportive functions.
- PI3K regulates an early step during viral entry, results in inhibition of premature apoptosis at later stages of infection.
Effects:
PI3K signaling pathway supports viral propagation.
Reference:
Ehrhardt, C. and Ludwig, S. (2009) A new player in a deadly game: influenza viruses and the PI3K/Akt signalling pathway. Cell Microbiol 11, 863-871.
