Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus

Zhaojing Hao1, Li Zheng1, Lan Kluwe2, Weida Huang1,31Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 2Laboratory for Tumor Biology and Developmental Disorders, Department of Maxillofacial Surgery, University Hospital Hamburg-...

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Autores principales: Huang WD, Kluwe L, Zheng L, Hao ZJ
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:c0c7b25576bc4fc5ba1f7089968375872021-12-02T07:20:24ZFerritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus1176-91141178-2013https://doaj.org/article/c0c7b25576bc4fc5ba1f7089968375872012-02-01T00:00:00Zhttp://www.dovepress.com/ferritin-light-chain-and-squamous-cell-carcinoma-antigen-1-are-corecep-a9275https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Zhaojing Hao1, Li Zheng1, Lan Kluwe2, Weida Huang1,31Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 2Laboratory for Tumor Biology and Developmental Disorders, Department of Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, Germany; 3Laboratory for Synthetic Biology, Centers for Nano-Medicine, Shanghai, People’s Republic of ChinaAbstract: Overexpression of squamous cell carcinoma antigen 1 (SCCA1) in hepatitis G2 (HepG2) and Chinese hamster ovary cells can increase hepatitis B virus (HBV) binding capacity by interacting with the preS1 domain of the HBV surface antigen. However, the magnitude of increase in binding capacity was higher by several orders in the former, indicating the existence of additional factor(s) produced by HepG2 cells, which facilitates HBV attachment. Ferritin light chain (FTL) was identified as the sole high hit candidate by screening human liver cDNA library using a bacterial two-hybrid system with either preS or SCCA1 as the bait. Subsequent in vitro protein–protein interaction assays confirmed the binding activity of FTL to both preS and SCCA1, as well as the formation of triple complex preS-FTL-SCCA1, and narrowed down the binding sites on FTL. In vitro overexpression of FTL could further enhance HBV attachment in both HepG2 and Chinese hamster ovary cells, which were already overexpressing SCCA1. Importantly, in vivo co-expression of human FTL and SCCA1 in mouse liver by means of tail-vein hydrodynamic injection increased serum levels of HBV surface antigen transiently 24 hours post challenge with HBV-positive human sera, and a large amount of HBV core antigen-positive hepatocytes around blood vessels could be identified by immunohistochemical staining 48 hours post challenge. The data strongly suggest that FTL and SCCA1 may serve as coreceptors in HBV cellular attachment and virus entry into hepatocytes.Keywords: squamous cell carcinoma antigen 1, ferritin light chain, hepatitis B virus, coreceptorsHuang WDKluwe LZheng LHao ZJDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 827-834 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Huang WD
Kluwe L
Zheng L
Hao ZJ
Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus
description Zhaojing Hao1, Li Zheng1, Lan Kluwe2, Weida Huang1,31Department of Biochemistry, School of Life Sciences, Fudan University, Shanghai, People’s Republic of China; 2Laboratory for Tumor Biology and Developmental Disorders, Department of Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, Germany; 3Laboratory for Synthetic Biology, Centers for Nano-Medicine, Shanghai, People’s Republic of ChinaAbstract: Overexpression of squamous cell carcinoma antigen 1 (SCCA1) in hepatitis G2 (HepG2) and Chinese hamster ovary cells can increase hepatitis B virus (HBV) binding capacity by interacting with the preS1 domain of the HBV surface antigen. However, the magnitude of increase in binding capacity was higher by several orders in the former, indicating the existence of additional factor(s) produced by HepG2 cells, which facilitates HBV attachment. Ferritin light chain (FTL) was identified as the sole high hit candidate by screening human liver cDNA library using a bacterial two-hybrid system with either preS or SCCA1 as the bait. Subsequent in vitro protein–protein interaction assays confirmed the binding activity of FTL to both preS and SCCA1, as well as the formation of triple complex preS-FTL-SCCA1, and narrowed down the binding sites on FTL. In vitro overexpression of FTL could further enhance HBV attachment in both HepG2 and Chinese hamster ovary cells, which were already overexpressing SCCA1. Importantly, in vivo co-expression of human FTL and SCCA1 in mouse liver by means of tail-vein hydrodynamic injection increased serum levels of HBV surface antigen transiently 24 hours post challenge with HBV-positive human sera, and a large amount of HBV core antigen-positive hepatocytes around blood vessels could be identified by immunohistochemical staining 48 hours post challenge. The data strongly suggest that FTL and SCCA1 may serve as coreceptors in HBV cellular attachment and virus entry into hepatocytes.Keywords: squamous cell carcinoma antigen 1, ferritin light chain, hepatitis B virus, coreceptors
format article
author Huang WD
Kluwe L
Zheng L
Hao ZJ
author_facet Huang WD
Kluwe L
Zheng L
Hao ZJ
author_sort Huang WD
title Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus
title_short Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus
title_full Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus
title_fullStr Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus
title_full_unstemmed Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus
title_sort ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis b virus
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/c0c7b25576bc4fc5ba1f708996837587
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AT zhengl ferritinlightchainandsquamouscellcarcinomaantigen1arecoreceptorsforcellularattachmentandentryofhepatitisbvirus
AT haozj ferritinlightchainandsquamouscellcarcinomaantigen1arecoreceptorsforcellularattachmentandentryofhepatitisbvirus
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