{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:54:26Z","timestamp":1791190466132,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"16","license":[{"start":{"date-parts":[[2012,8,15]],"date-time":"2012-08-15T00:00:00Z","timestamp":1344988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2012,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Hepatitis C virus (HCV) induces autophagosome formation in infected human hepatocytes. We have previously reported that HCV exploits autophagic machinery in favor of virus growth and survival in host cells (S. Shrivastava et al., Hepatology\n            <jats:bold>53:<\/jats:bold>\n            406\u2013414, 2011); however, the mechanisms for autophagy induction is poorly understood. In the present study, we observed that HCV infection transcriptionally upregulates Beclin1, which forms complex with Vps34, the class III phosphatidylinositol 3-kinase, as a first step for autophagy initiation. Although Bcl-2 has an anti-autophagy effect by its association with Beclin1 in nutrient-deprived cells, our studies revealed that HCV-mediated autophagy occurs independent of Beclin1\u2013Bcl-2 dissociation. Mammalian target of rapamycin (mTOR) is a positive regulator of cell growth and is recognized as an inhibitor of autophagy induction. Our results demonstrated that HCV infection enhances phospho-mTOR expression and its downstream target 4EBP1 activation, suggesting that mTOR is not a negative regulator of HCV-induced autophagy. On the other hand, HCV infection in autophagy-impaired cells reduced phospho-mTOR, mTOR, and phospho-4EBP1 expression. Together, these results suggested that HCV induces autophagy by upregulating Beclin1 and activates mTOR signaling pathway, which in turn may promote hepatocyte growth.\n          <\/jats:p>","DOI":"10.1128\/jvi.00616-12","type":"journal-article","created":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T01:11:02Z","timestamp":1339031462000},"page":"8705-8712","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":149,"title":["Hepatitis C Virus Upregulates Beclin1 for Induction of Autophagy and Activates mTOR Signaling"],"prefix":"10.1128","volume":"86","author":[{"given":"Shubham","family":"Shrivastava","sequence":"first","affiliation":[{"name":"Departments of Pathology, Saint Louis University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joydip","family":"Bhanja Chowdhury","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Saint Louis University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Steele","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Saint Louis University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjit","family":"Ray","sequence":"additional","affiliation":[{"name":"Internal Medicine, Saint Louis University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratna B.","family":"Ray","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Saint Louis University, St. Louis, Missouri, USA"},{"name":"Internal Medicine, Saint Louis University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02093-07"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-144-10-200605160-00004"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200803137"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10963"},{"key":"e_1_3_2_6_2","first-page":"169","article-title":"Early embryonic lethality in mice deficient in the p110beta catalytic subunit of PI 3-kinase","volume":"13","author":"Bi L","year":"2002","unstructured":"BiL OkabeI BernardDJ NussbaumRL. 2002. 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