Viral Replication Complexes Are Targeted by LC3-Guided Interferon-Inducible GTPases Cell Host Microbe. 2017 Jul 12;22(1):74-85.e7. Biering SB, Choi J, Halstrom RA, Brown HM, et al. Speaker: Zi-Yi Lu(呂姿儀) Time: 13:10-14:00, Nov. 8. 2017 Commentator: Dr. Yao Chang (張堯 老師) Place: Room 601 Abstract: Many clinical viral diseases are caused by positive –sense RNA (+RNA) viruses. After viruses infect and get into cells, they will form replication complexes (RCs) in cytoplasm, which serve as a shelter to help their replication [1]. However, it remains unclear how viral RC interacts with host immune responses. According to author’s previous studies, they demonstrated that IFN-gamma (IFNG) is able to inhibit the replication and RCs formation of murine norovirus (MNV), which is a member of norovirus within Caliciviridae [2]. In this paper, authors further revealed that IFNG destroys MNV RC via autophagy related proteins and IFN-inducible GTPases. They found that LC3 conjugation system of autophagy could target MNV RC, and then guide IFN-inducible GTPases, including immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs) to MNV RC under IFNG treatment. This inhibited MNV RC formation and replication both in vitro and in vivo. At last, authors proved that LC3 conjugation system and GBPs are both required for IFNG-mediated suppression of MNV replication as well as in human cells. These data give us a new insight that hosts might utilize this same strategy, as LC3 conjugation system and IFN-inducible GTPases, to target cytosolic membrane structures where they replicate and can control intracellular pathogens including protists, bacteria and viruses. 1. den Boon JA, Diaz A, Ahlquist P. Cytoplasmic viral replication complexes. Cell Host Microbe. 2010 Jul 22;8(1):77-85. 2. Hwang S, Maloney NS, Bruinsma MW, et al. Nondegradative role of Atg5-Atg12/ Atg16L1 autophagy protein complex in antiviral activity of interferon gamma. Cell Host Microbe. 2012 Apr 19;11(4):397-409.