{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T02:16:02Z","timestamp":1740104162034,"version":"3.37.3"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T00:00:00Z","timestamp":1602115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fulminant hepatic failure (FHF) is a lethal manifestation of hepatitis A virus (HAV) infection, whose underlying mechanisms are poorly understood. We aimed to evaluate the importance of the modulation of the RANTES\u2010chemokine receptor type 5 (CCR5) signaling axis and its immunomodulatory effects in directing hepatitis A disease pathogenesis using an in silico, in vitro and patient cohort\u2010based approach.\u00a0In silico interaction studies were performed using computation approaches with suitable software. Differential expression of relevant cytokines and immune cell markers were studied using real\u2010time quantitative reverse transcription PCR (qRT\u2010PCR), enzyme\u2010linked immunosorbent assay, and flow\u2010cytometry\u2010based methods. In the HepG2 cell line, we studied inflammatory responses and susceptibility to HAV infection following RANTES stimulation and antibody blockade of CCR5. The HAV\u2010VP3 region exhibited high interaction in CCR5: HAV complexes. RANTES levels were significantly increased in FHF cases. Reduced monocyte and T\u2010cell activation were observed in FHF cases. RANTES expression inversely correlated with viremia but positively correlated with proinflammatory responses. Hyper Th1\u2010biased immune responses, marked by high interleukin (IL)\u201012\/IL\u201010 ratio were observed in FHF cases, which were also characterized by upregulated tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) expression and reduced interferon\u2010gamma expression. In vitro, RANTES was protective against HAV infection but resulted in upregulated TNF\u2010\u03b1 expression. Although viral load increased upon the regulation of inflammatory responses by CCR5 blocking, it was still significantly lower compared to control HAV\u2010infected cells. Our study suggests the importance of RANTES\u2010CCR5 signaling and linked\u2010immunomodulation in HAV disease pathogenesis, as well as highlights the utility of CCR5 antagonists as a risk\u2010reduction strategy in FHF patients. Our findings, therefore, have important implications for the management of high\u2010risk HAV infections.<\/jats:p>","DOI":"10.1002\/jmv.26557","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T13:26:55Z","timestamp":1601040415000},"page":"3656-3665","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prognostic, clinical, and therapeutic importance of RANTES\u2010CCR5 axis in hepatitis A infection: A multiapproach study"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-7785","authenticated-orcid":false,"given":"Vargab","family":"Baruah","sequence":"first","affiliation":[{"name":"Department of Biotechnology Gauhati University Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diptika","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Gauhati University Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajib Kishore","family":"Hazam","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Gauhati University Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moumita","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Gauhati University Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dipankar","family":"Bujarbaruah","sequence":"additional","affiliation":[{"name":"Department of Zoology Dimoria College Khetri Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjan Kumar","family":"Saikia","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology GNRC Hospital Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Premashish","family":"Kar","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Gauhati University Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sangit","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology GMCH Hospital Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3606-958X","authenticated-orcid":false,"given":"Sujoy","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Gauhati University Guwahati Assam India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0264-410X(92)90535-R"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2013.03.013"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.21865"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)30579-7"},{"issue":"6","key":"e_1_2_9_6_1","first-page":"1071","article-title":"Vaccination against hepatitis A in children: a review of the evidence","volume":"3","author":"Bonanni P","year":"2007","journal-title":"Ther Clin Risk Manag"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.20475"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.5005\/jp-journals-10018-1181"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12606"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2013.37"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001340050554"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4906(00)01812-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2013.0067"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-783x-15-3-97"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12476"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/524692"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/36129"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.1.552"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.12.011"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/MI.2005.343"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.10.1939"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06784-x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.169"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.15761\/ghe.1000153"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(89)90081-4"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-018-3417-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1298"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.12.6180"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2020.01.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428199809050903"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011059906777"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200108)31:8<2411::AID-IMMU2411>3.0.CO;2-Y"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.4.2729-a"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.11.6236"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224523"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2008.00978.x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/84209"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri722"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6642"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01981"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0b013e3283223d76"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.26557","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.26557","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.26557","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T05:42:34Z","timestamp":1697089354000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.26557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,8]]},"references-count":40,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/jmv.26557"],"URL":"https:\/\/doi.org\/10.1002\/jmv.26557","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"type":"print","value":"0146-6615"},{"type":"electronic","value":"1096-9071"}],"subject":[],"published":{"date-parts":[[2020,10,8]]},"assertion":[{"value":"2020-08-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}