Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus.
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Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus. / Hao, Zhaojing; Zheng, Li; Kluwe, Lan; Huang, Weida.
in: INT J NANOMED, Jahrgang 7, 2012, S. 827-834.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Ferritin light chain and squamous cell carcinoma antigen 1 are coreceptors for cellular attachment and entry of hepatitis B virus.
AU - Hao, Zhaojing
AU - Zheng, Li
AU - Kluwe, Lan
AU - Huang, Weida
PY - 2012
Y1 - 2012
N2 - 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 tailvein 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.
AB - 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 tailvein 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.
KW - Animals
KW - Humans
KW - Male
KW - Mice
KW - CHO Cells
KW - Cricetinae
KW - Cricetulus
KW - Amino Acid Sequence
KW - Two-Hybrid System Techniques
KW - Protein Structure, Tertiary
KW - Sequence Alignment
KW - Hep G2 Cells
KW - Protein Interaction Mapping
KW - Host-Pathogen Interactions
KW - Antigens, Neoplasm/chemistry/genetics/metabolism
KW - Apoferritins/chemistry/genetics/metabolism
KW - Hepatitis B/virology
KW - Hepatitis B Surface Antigens/chemistry/metabolism
KW - Hepatitis B virus/metabolism/physiology
KW - Serpins/chemistry/genetics/metabolism
KW - Virus Attachment
KW - Animals
KW - Humans
KW - Male
KW - Mice
KW - CHO Cells
KW - Cricetinae
KW - Cricetulus
KW - Amino Acid Sequence
KW - Two-Hybrid System Techniques
KW - Protein Structure, Tertiary
KW - Sequence Alignment
KW - Hep G2 Cells
KW - Protein Interaction Mapping
KW - Host-Pathogen Interactions
KW - Antigens, Neoplasm/chemistry/genetics/metabolism
KW - Apoferritins/chemistry/genetics/metabolism
KW - Hepatitis B/virology
KW - Hepatitis B Surface Antigens/chemistry/metabolism
KW - Hepatitis B virus/metabolism/physiology
KW - Serpins/chemistry/genetics/metabolism
KW - Virus Attachment
U2 - 10.2147/IJN.S27803
DO - 10.2147/IJN.S27803
M3 - SCORING: Journal article
VL - 7
SP - 827
EP - 834
JO - INT J NANOMED
JF - INT J NANOMED
SN - 1178-2013
ER -
