The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Export

@article{citeulike:3125137, abstract = {Autophagy is an essential process for physiological homeostasis, but its role in viral infection is only beginning to be elucidated. We show here that the Atg5-Atg12 conjugate, a key regulator of the autophagic process, plays an important role in innate antiviral immune responses. Atg5-deficient mouse embryonic fibroblasts (MEFs) were resistant to vesicular stomatitis virus replication, which was largely due to hyperproduction of type I interferons in response to immunostimulatory RNA (isRNA), such as virus-derived, double-stranded, or 5'-phosphorylated RNA. Similar hyperresponse to isRNA was also observed in Atg7-deficient MEFs, in which Atg5-Atg12 conjugation is impaired. Overexpression of Atg5 or Atg12 resulted in Atg5-Atg12 conjugate formation and suppression of isRNA-mediated signaling. Molecular interaction studies indicated that the Atg5-Atg12 conjugate negatively regulates the type I IFN production pathway by direct association with the retinoic acid-inducible gene I (RIG-I) and IFN-beta promoter stimulator 1 (IPS-1) through the caspase recruitment domains (CARDs). Thus, in contrast to its role in promoting the bactericidal process, a component of the autophagic machinery appears to block innate antiviral immune responses, thereby contributing to RNA virus replication in host cells.}, address = {Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.}, author = {Jounai, N. and Takeshita, F. and Kobiyama, K. and Sawano, A. and Miyawaki, A. and Xin, K. Q. and Ishii, K. J. and Kawai, T. and Akira, S. and Suzuki, K. and Okuda, K.}, citeulike-article-id = {3125137}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0704014104}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17709747}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17709747}, day = {28}, doi = {10.1073/pnas.0704014104}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {atg12, atg5, autophagy, innate\_immunity, viral\_immunity}, month = {August}, number = {35}, pages = {14050--14055}, posted-at = {2008-08-15 01:01:02}, priority = {0}, title = {The Atg5 Atg12 conjugate associates with innate antiviral immune responses.}, url = {http://dx.doi.org/10.1073/pnas.0704014104}, volume = {104}, year = {2007} }

TY - JOUR ID - citeulike:3125137 L3 - citeulike-article-id:3125137 N2 - Autophagy is an essential process for physiological homeostasis, but its role in viral infection is only beginning to be elucidated. We show here that the Atg5-Atg12 conjugate, a key regulator of the autophagic process, plays an important role in innate antiviral immune responses. Atg5-deficient mouse embryonic fibroblasts (MEFs) were resistant to vesicular stomatitis virus replication, which was largely due to hyperproduction of type I interferons in response to immunostimulatory RNA (isRNA), such as virus-derived, double-stranded, or 5'-phosphorylated RNA. Similar hyperresponse to isRNA was also observed in Atg7-deficient MEFs, in which Atg5-Atg12 conjugation is impaired. Overexpression of Atg5 or Atg12 resulted in Atg5-Atg12 conjugate formation and suppression of isRNA-mediated signaling. Molecular interaction studies indicated that the Atg5-Atg12 conjugate negatively regulates the type I IFN production pathway by direct association with the retinoic acid-inducible gene I (RIG-I) and IFN-beta promoter stimulator 1 (IPS-1) through the caspase recruitment domains (CARDs). Thus, in contrast to its role in promoting the bactericidal process, a component of the autophagic machinery appears to block innate antiviral immune responses, thereby contributing to RNA virus replication in host cells. IS - 35 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 AD - Department of Molecular Biodefense Research, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan. EP - 14055 TI - The Atg5 Atg12 conjugate associates with innate antiviral immune responses. VL - 104 SP - 14050 KW - atg12 KW - atg5 KW - autophagy KW - innate_immunity KW - viral_immunity AU - Jounai, N AU - Takeshita, F AU - Kobiyama, K AU - Sawano, A AU - Miyawaki, A AU - Xin, KQ AU - Ishii, KJ AU - Kawai, T AU - Akira, S AU - Suzuki, K AU - Okuda, K PY - 2007/08/28/ UR - http://dx.doi.org/10.1073/pnas.0704014104 ER -