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However, the mechanisms by which HBV evades host immunity and maintains chronic infection are largely unknown. Here, we revealed that matrix metalloproteinase 9 (MMP-9) is activated in peripheral blood mononuclear cells (PBMCs) of HBV-infected patients, and HBV stimulates MMP-9 expression in macrophages and PBMCs isolated from healthy individuals. MMP-9 plays important roles in the breakdown of the extracellular matrix and in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. MMP-9 also regulates respiratory syncytial virus (RSV) replication, but the mechanism underlying such regulation is unknown. We further demonstrated that MMP-9 facilitates HBV replication by repressing the interferon (IFN)\/Janus kinase (JAK)\/signal transducer and activator of transcription (STAT) pathway, IFN action, STAT1\/2 phosphorylation, and IFN-stimulated gene (ISG) expression. Moreover, MMP-9 binds to type I IFN receptor 1 (IFNAR1) and facilitates IFNAR1 phosphorylation, ubiquitination, subcellular distribution, and degradation to interfere with the binding of IFANR1 to IFN-\u03b1. Thus, we identified a novel positive-feedback regulation loop between HBV replication and MMP-9 production. On one hand, HBV activates MMP-9 in infected patients and leukocytes. On the other hand, MMP-9 facilitates HBV replication through repressing IFN\/JAK\/STAT signaling, IFNAR1 function, and IFN-\u03b1 action. Therefore, HBV may take the advantage of MMP-9 function to establish or maintain chronic infection.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Hepatitis B virus (HBV) infection may cause chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). However, the mechanisms by which HBV maintains chronic infection are largely unknown. Matrix metalloproteinase 9 (MMP-9) plays important roles in the facilitation of tumor progression, invasion, metastasis, and angiogenesis. However, the effects of MMP-9 on HBV replication and pathogenesis are not known. This study reveals that MMP-9 expression is activated in patients with CHB, and HBV stimulates MMP-9 production in PBMCs and macrophages. More interestingly, MMP-9 in turn promotes HBV replication through suppressing IFN-\u03b1 action. Moreover, MMP-9 interacts with type I interferon receptor 1 (IFNAR1) to disturb the binding of IFN-\u03b1 to IFNAR1 and facilitate the phosphorylation, ubiquitination, subcellular distribution, and degradation of IFNAR1. Therefore, these results discover a novel role of MMP-9 in viral replication and reveal a new mechanism by which HBV evades host immunity to maintain persistent infection.\n          <\/jats:p>","DOI":"10.1128\/jvi.01824-16","type":"journal-article","created":{"date-parts":[[2017,1,26]],"date-time":"2017-01-26T01:12:55Z","timestamp":1485393175000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":66,"title":["Matrix Metalloproteinase 9 Facilitates Hepatitis B Virus Replication through Binding with Type I Interferon (IFN) Receptor 1 To Repress IFN\/JAK\/STAT Signaling"],"prefix":"10.1128","volume":"91","author":[{"given":"Junbo","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanni","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Xie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yecheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunqiang","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailang","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingle","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and College of Life Sciences, Wuhan University, Wuhan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/epirev\/mxj009"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60207-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.061"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.02.031"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-014-0331-5"},{"key":"e_1_3_2_7_2","first-page":"71","article-title":"The receptor of the type I interferon family","volume":"316","author":"Uz\u00e9 G","year":"2007","unstructured":"Uz\u00e9 G Schreiber G Piehler J Pellegrini S . 2007. 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