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We previously revealed a crucial role for the ERK1\/2 signaling pathway in regulating viral infectivity. However, the detail mechanism remains largely unknown. Grb2\u2010associated binder 1 (GAB1) is an important docking protein responsible for intracellular signaling assembly and transduction. In this study, we demonstrated that GAB1 was proteolytically cleaved after CVB3 infection at G175 and G436 by virus\u2010encoded protease 2A\n                    <jats:sup>pro<\/jats:sup>\n                    , independent of caspase activation. Knockdown of GAB1 resulted in a significant reduction of viral protein expression and virus titers. Moreover, we showed that virus\u2010induced cleavage of GAB1 is beneficial to viral growth as the N\u2010terminal proteolytic product of GAB1 (GAB1\u2010N\n                    <jats:sub>1\u2010174<\/jats:sub>\n                    ) further enhances ERK1\/2 activation and promotes viral replication. Our results collectively suggest that CVB3 targets host GAB1 to generate a GAB1\u2010N\n                    <jats:sub>1\u2010174<\/jats:sub>\n                    fragment that enhances viral infectivity, at least in part,\n                    <jats:italic>via<\/jats:italic>\n                    activation of the ERKpathway. The findings in this study suggest a novel mechanism that CVB3 employs to subvert the host signaling and facilitate consequent viral replication.\u2014Deng, H., Fung, G., Shi, J., Xu, S., Wang, C., Yin, M., Hou, J., Zhang, J., Jin, Z.\u2010G., Luo, H. Enhanced enteroviral infectivity\n                    <jats:italic>via<\/jats:italic>\n                    viral protease\u2010mediated cleavage of Grb2\u2010associated binder 1.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    29, 4523\u20104531 (2015).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.15-274829","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T22:40:25Z","timestamp":1437086425000},"page":"4523-4531","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Enhanced enteroviral infectivity\n                    <i>via<\/i>\n                    viral protease\u2010mediated cleavage of Grb2\u2010associated binder 1"],"prefix":"10.1096","volume":"29","author":[{"given":"Haoyu","family":"Deng","sequence":"first","affiliation":[{"name":"Centre for Heart Lung Innovation St. Paul's Hospital Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Fung","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation St. Paul's Hospital Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyan","family":"Shi","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation St. Paul's Hospital Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suowen","family":"Xu","sequence":"additional","affiliation":[{"name":"Aab Cardiovascular Research Institute and Department of Medicine University of Rochester School of Medicine and Dentistry Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation St. Paul's Hospital Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meimei","family":"Yin","sequence":"additional","affiliation":[{"name":"Aab Cardiovascular Research Institute and Department of Medicine University of Rochester School of Medicine and Dentistry Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Hou","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation St. Paul's Hospital Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingchun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation St. Paul's Hospital Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zheng\u2010Gen","family":"Jin","sequence":"additional","affiliation":[{"name":"Aab Cardiovascular Research Institute and Department of Medicine University of Rochester School of Medicine and Dentistry Rochester New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Honglin","family":"Luo","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung Innovation St. Paul's Hospital Department of Pathology and Laboratory Medicine University of British Columbia Vancouver British Columbia Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,7,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pathmechdis.3.121806.151534"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.11.009"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp225"},{"key":"e_1_2_7_5_1","first-page":"177","article-title":"The impact of CVB3 infection on host cell biology","volume":"323","author":"Marchant D.","year":"2008","journal-title":"Curr. 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