{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:26:11Z","timestamp":1790627171336,"version":"4.1.0"},"reference-count":46,"publisher":"Microbiology Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,6,1]]},"abstract":"<jats:p>The ORF3 protein of hepatitis E virus (HEV), the precise cellular functions of which remain obscure, was used in a yeast two-hybrid screen to identify its cellular binding partners. One of the identified interacting partners was fibrinogen B<jats:italic>\u03b2<\/jats:italic>protein. The ORF3\u2013fibrinogen B<jats:italic>\u03b2<\/jats:italic>interaction was verified by co-immunoprecipitation and fluorescence resonance energy transfer in mammalian cells. Fibrinogen is a hepatic acute-phase protein and serves as a central molecule that maintains host homeostasis and haemostasis during an acute-phase response. Metabolic labelling of ORF3-transfected HuH-7 cells showed that secreted as well as intracellular levels of fibrinogen were decreased in these cells compared with vector-transfected controls. Northern hybridization and RT-PCR analyses revealed that the mRNA levels of all three chains of fibrinogen, A<jats:italic>\u03b1<\/jats:italic>, B<jats:italic>\u03b2<\/jats:italic>and<jats:italic>\u03b3<\/jats:italic>, were transcriptionally downregulated in ORF3-transfected cells. The constitutive expression of fibrinogen genes can be significantly upregulated by interleukin (IL)-6, an important mediator of liver-specific gene expression during an acute-phase response. Transcription of fibrinogen genes after IL-6 stimulation was less in ORF3-expressing cells compared with controls. This report adds one more biological function to, and advances our understanding of, the cellular role of the ORF3 protein of HEV. The possible implications of these findings in the virus life cycle are discussed.<\/jats:p>","DOI":"10.1099\/vir.0.009274-0","type":"journal-article","created":{"date-parts":[[2009,5,18]],"date-time":"2009-05-18T18:28:53Z","timestamp":1242671333000},"page":"1359-1370","source":"Crossref","is-referenced-by-count":28,"title":["ORF3 protein of hepatitis E virus interacts with the B\u03b2 chain of fibrinogen resulting in decreased fibrinogen secretion from HuH-7 cells"],"prefix":"10.1099","volume":"90","author":[{"given":"Ruchi","family":"Ratra","sequence":"first","affiliation":[{"name":"Virology Group, International Centre for Genetic Engineering and Biotechnology, PO Box 10504, Aruna Asaf Ali Road, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anindita","family":"Kar-Roy","sequence":"additional","affiliation":[{"name":"Virology Group, International Centre for Genetic Engineering and Biotechnology, PO Box 10504, Aruna Asaf Ali Road, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil K.","family":"Lal","sequence":"additional","affiliation":[{"name":"Virology Group, International Centre for Genetic Engineering and Biotechnology, PO Box 10504, Aruna Asaf Ali Road, New Delhi 110067, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"1847","DOI":"10.1016\/S0021-9258(18)53932-6","article-title":"The structural motif glycine 190-valine 202 of the fibrinogen \u03b3 chain interacts with CD11b\/CD18 integrin ( \u03b1 M \u03b2 2, Mac-1) and promotes leukocyte adhesion","volume":"268","author":"Altieri","year":"1993","journal-title":"J Biol Chem"},{"key":"R2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0049-3848(96)00111-9","article-title":"Fibrinogen and fibrin \u2013 proteins with complex roles in hemostasis and thrombosis","volume":"83","author":"Blomback","year":"1996","journal-title":"Thromb Res"},{"key":"R3","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.1128\/JVI.00403-08","article-title":"The hepatitis E virus ORF3 protein modulates epidermal growth factor receptor trafficking, STAT3 translocation, and the acute-phase response","volume":"82","author":"Chandra","year":"2008","journal-title":"J Virol"},{"key":"R4","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.1016\/S0021-9258(18)34368-0","article-title":"Coordinate accumulation of the mRNAs for the \u03b1 , \u03b2 , and \u03b3 chains of rat fibrinogen following defibrination","volume":"257","author":"Crabtree","year":"1982","journal-title":"J Biol Chem"},{"key":"R5","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/0167-4781(90)90057-9","article-title":"Intracellular fate of fibrinogen B \u03b2 chain expressed in COS cells","volume":"1048","author":"Danishefsky","year":"1990","journal-title":"Biochim Biophys Acta"},{"key":"R6","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1055\/s-0038-1646385","article-title":"Inflammation and coagulation: linked processes potentially regulated through a common pathway mediated by protein C","volume":"66","author":"Esmon","year":"1991","journal-title":"Thromb Haemost"},{"key":"R7","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1749-6632.2001.tb03534.x","article-title":"Transcriptional control mechanism of fibrinogen gene expression","volume":"936","author":"Fuller","year":"2001","journal-title":"Ann N Y Acad Sci"},{"key":"R8","doi-asserted-by":"crossref","first-page":"5919","DOI":"10.1128\/JVI.00046-06","article-title":"A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus","volume":"80","author":"Graff","year":"2006","journal-title":"J Virol"},{"key":"R9","doi-asserted-by":"crossref","first-page":"3018","DOI":"10.1128\/JVI.02259-06","article-title":"Initiation at the third in-frame AUG codon of open reading frame 3 of the hepatitis E virus is essential for viral infectivity in vivo","volume":"81","author":"Huang","year":"2007","journal-title":"J Virol"},{"key":"R10","doi-asserted-by":"crossref","first-page":"5695","DOI":"10.1016\/S0021-9258(19)39419-0","article-title":"Human \u03b2 -fibrinogen gene expression. 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