The non-canonical role of Atg family members as suppressors of innate antiviral immune signaling.
Recent research on autophagy clearly demonstrates that the autophagosome-lysosome pathway plays essential roles in elimination of certain pathogens such as group A Streptococcus, Mycobacterium tuberculosis, Listeria monocytogenes, and herpesvirus. (1-4) We have recently found that a key regulator of the autophagic process, the Atg12-Atg5 conjugate, associates with the signaling molecules retinoic acid-inducible gene I (RIG-I) and interferon-beta promoter stimulator 1 (IPS-1), which are essential for recognition of RNA virus infection and which transmit signals to upregulate type I interferons (IFNs). Interestingly, the Atg12-Atg5 conjugate seemed to negatively regulate the type I IFN modulating pathway through direct interaction with caspase recruitment domains (CARDs) presented by RIG-1 and IPS-1.(5) Thus, in contrast to the bactericidal properties of autophagic processes, the autophagy regulator (the Atg12-Atg5 conjugate) appeared to promote RNA virus replication by inhibiting innate anti-virus immune responses. In this addendum, we discuss the non-canonical role of the Atg12-Atg5 conjugate as a suppressor of innate immune responses.
Takeshita
Fumihiko
F
Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Yokohama, Japan. takesita@yokohama-cu.ac.jp
Kobiyama
Kouji
K
Miyawaki
Atsushi
A
Jounai
Nao
N
Okuda
Kenji
K
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D010588:Phagosomes / Q000378:metabolism; D012328:RNA Viruses / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D011971:Receptors, Immunologic; D015398:Signal Transduction / Q000502:physiology*; D014777:Virus Diseases / Q000276:immunology; D014779:Virus Replication
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; C505371:MAVS protein, human; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases