| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Zhao, Ping Li, Qiao Zhang, Xiao-Lian Tao, Wanyin Zhao, Yinglan Zhang, Xuping Zhong, Jin Ren, Yushan |
| Description |
Author Affiliation: Zhao Y ( State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan 430071, China); Ren Y ( State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan 430071, China); Zhang X ( State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan 430071, China); Zhao P ( Department of Microbiology, Second Military Medical University, Shanghai 200433, China); Tao W ( Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai 200025, China); Zhong J ( Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Shanghai 200025, China); Li Q ( University of Michigan Medical Center, Ann Arbor, MI 48109.); Zhang XL ( State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University School of Medicine, Wuhan 430071, China) |
| Abstract |
Human ficolin-2 (L-ficolin/p35) is a lectin-complement pathway activator that is present in normal human plasma and is associated with infectious diseases; however, little is known regarding the roles and mechanisms of ficolin-2 during chronic hepatitis C virus (HCV) infection. In this study, we found that ficolin-2 inhibits the entry of HCV at an early stage of viral infection, regardless of the viral genotype. Ficolin-2 neutralized and inhibited the initial attachment and infection of HCV by binding to the HCV envelope surface glycoproteins E1 and E2, blocking HCV attachment to low-density lipoprotein receptor (LDLR) and scavenger receptor B1, and weakly interfering with CD81 receptor attachment. However, no interference with claudin-1 and occludin receptor attachment was observed. The C-terminal fibrinogen domain (201-313 aa) of ficolin-2 was identified as the critical binding region for the HCV-E1-E2 N-glycans, playing a critical role in the anti-HCV activity. More importantly, we found that apolipoprotein E (ApoE)3, which is enriched in the low-density fractions of HCV RNA-containing particles, promotes HCV infection and inhibits ficolin-2-mediated antiviral activity. ApoE3, but not ApoE2 and ApoE4, blocked the interaction between ficolin-2 and HCV-E2. Our data suggest that the HCV entry inhibitor ficolin-2 is a novel and promising antiviral innate immune molecule, whereas ApoE3 blocks the effect of ficolin-2 and mediates an immune escape mechanism during chronic HCV infection. HCV may be neutralized using compounds directed against the lipoprotein moiety of the viral particle, and ApoE3 may be a new target to combat HCV infection. |
| ISSN |
00221767 |
| e-ISSN |
15506606 |
| Journal |
The Journal of Immunology |
| Issue Number |
2 |
| Volume Number |
193 |
| Language |
English |
| Publisher |
The American Association of Immunologists |
| Publisher Date |
2014-07-15 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Apolipoprotein E3 Immunology Hepacivirus Lectins Tumor Escape Antigens, Cd81 Genetics Metabolism Binding, Competitive Blotting, Western Cell Line, Tumor Green Fluorescent Proteins Hek293 Cells Hela Cells Physiology Host-pathogen Interactions Mannans Microscopy, Confocal Polysaccharides Protein Binding Rna Interference Receptors, Ldl Scavenger Receptors, Class B Viral Envelope Proteins Research Support, Non-u.s. Gov't Discipline Immunology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Immunology and Allergy Immunology |
