Induction of stress granules by interferon and down-regulation by the cellular RNA adenosine deaminase ADAR1

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Measles virus (MV) infection impacts cellular innate immune responses.
• Stress granules (SG) and interferon (IFN) are key antiviral defense mechanisms.
• The roles of specific MV proteins and IFN-inducible factors in SG formation are not fully understood.

Purpose of the Study:

• To investigate the induction of stress granules (SG) by measles virus (MV) variants.
• To determine the role of interferon-beta (IFNβ) pretreatment in SG formation.
• To elucidate the involvement of protein kinase R (PKR) and ADAR1 in the IFN-mediated SG response.

Main Methods:

• Infection of cells with wild-type (WT), C protein-deficient (C(ko)), and V protein-deficient (V(ko)) MV.
• IFNβ pretreatment of cells prior to viral infection.
• Assessment of SG formation.
• Analysis of PKR and ADAR1 involvement using genetic or pharmacological approaches.
• Investigation of STAT1 and STAT2 signaling pathways.

Main Results:

• C(ko) MV efficiently induced SG and IFNβ, unlike WT and V(ko) MV.
• IFNβ pretreatment enhanced SG formation in WT and V(ko) MV-infected cells, dependent on PKR.
• IFN treatment alone induced SG in ADAR1-deficient cells but not ADAR1-sufficient cells.
• IFN-induced SG formation relied on STAT1 and STAT2 signaling.

Conclusions:

• ADAR1 acts as a suppressor of both interferon and stress granule innate immune responses.
• The C protein of MV plays a critical role in modulating SG and IFN induction.
• IFN signaling pathways, involving PKR, STAT1, and STAT2, are crucial for SG formation during MV infection.