The Atg5-Atg12 conjugate associates with innate antiviral immune responses

PNAS, 2007, 104:14050-14055

Speaker: Yen-Chun Lin                        Date: 2007/9/19, 13:10~14:00

Commentator: Dr. Pin Ling                     Place: Room 601

Abstract:

Autophagy, also called type II programmed cell death, is characterized by the accumulation of autophagosome and autophagolysosome¹. Some evidences suggested that autophagy is associated with intracellular bacteria elimination², and some bacteria have ability to escape it. However, the role of autophagy in virus replication or elimination is still controversial. The study in this paper showed that Vesicular Stomatitis Virus (VSV) replication will induce autophagy in wild-type (WT) mouse embryonic fibroblast (MEFs), but not in Atg5 knockout (KO) MEFs. In addition, afterdsRNA [polyI:C] stimulation, the level of type I IFN, IP-10, IL-6 mRNA expression were higher in Atg5 KO MEFs than in WT MEFs. Increasing the expression of Atg5-Atg12 conjugate by transient transfection of Atg5 or Atg12 will decrease the expression of NF-kB and type I interferons. Mutated Atg5, which cannot conjugate with Atg12, would have these effects. Immunoprecipitating experiments showed that Atg5-Atg12 conjugate associated with RIG-1, MDA5, and the adapter protein, IPS-1, thus regulated the signal transduction of type I interferons. The Atg5-Atg12 conjugate binds to RIG-1 and IPS-1 through the CARD domain. The findings demonstrated that, in contrast to its role in promoting the bactericidal process, autophagic formation appear to block type I interferon production through RIG/IPS-1, CARD interaction, thereby contributing to RNA virus replication in host cells.

Reference:

1.      Shintani T at el., Autophagy in health and disease: A double-edged sword. Science. 2004, 306:990-995

2.      Gutierrez MG. at el., Autophagy defends cells against invading group A Streptococcus. Science. 2004 306:1037-1040