Crosstalk between the innate immune system and selective autophagy in hepatitis B virus infection

• Published in: Autophagy Vol. 18; no. 8; pp. 2006 - 2007
• Main Authors: Miyakawa, Kei, Jeremiah, Sundararaj Stanleyraj, Ogawa, Michinaga, Nishi, Mayuko, Ohnishi, Makoto, Ryo, Akihide
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.08.2022
• Subjects: Autophagic Punctum; Autophagy; BRET; Hepatitis B; Hepatitis B virus; Hepatocytes; Humans; Immune System; interferon; Macroautophagy; selective autophagy; Virus Replication; xenophagy; BRET; xenophagy; interferon; hepatitis B virus; selective autophagy
• ISSN: 1554-8627; 1554-8635; 1554-8635
• DOI: 10.1080/15548627.2022.2059747

Although the involvement of macroautophagy/autophagy in hepatitis B virus (HBV) infection has become clearer recently, whether selective autophagy plays an important role in suppressing HBV remains uncertain. We recently found that LGALS9 (galectin 9) is an interferon (IFN)-inducible protein involved in the suppression of HBV replication. Expression of LGALS9 in HBV-infected cells causes the formation of cytoplasmic puncta that degrade the HBV core protein (HBc) in conjunction with RSAD2/viperin, another IFN-inducible protein. LGALS9 binds to HBc via RSAD2 and promotes the autoubiquitination of RNF13 (ring finger protein 13) to recruit SQSTM1/p62, resulting in the formation of LC3-positive autophagosomes that degrade HBc. Both LGALS9 and RSAD2 are encoded by IFN-stimulated genes that act synergistically to induce HBc proteolysis in HBV-infected hepatocytes in an IFN-dependent manner. These results reveal a crosstalk mechanism between the innate immune system and selective autophagy during viral infection.