Three different functional microdomains in the hepatitis C virus hypervariable region 1 (HVR1) mediate entry and immune evasion
| Autor: | Hao Ren, Ping Zhao, Zhong-Tian Qi, Laure Aurelian, Xiaoqing Liu, Yongzhe Zhu, Yimin Tong, Thomas F. Baumert, Mo Guan, Jean Dubuisson, Wenbo Wang, Yuan Liu, Haoran Peng, Shi-Ying Zhu |
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| Přispěvatelé: | Second Military Medical University [Shanghai], Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Maryland School of Medicine, University of Maryland System, This work was supported by 973 Programme of China Research Grants 2009CB522501 and 2009CB522503, Important National Science and Technology Special Projects for Prevention and Treatment of Major Infectious Diseases Grant 2012ZX10002003-004-010, Natural Science Foundation of China Grants 81071364 and 31170150, Science Fund for Creative Research Groups, NSFC Grant 30921006, and Shanghai Leading Academic Discipline Project B901., Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
CD36 Antigens
MESH: Antibodies Neutralizing/pharmacology MESH: Immune Evasion MESH: CD36 Antigens/immunology viruses MESH: Antibodies Neutralizing/immunology Hepacivirus medicine.disease_cause Antibodies Viral MESH: Antibodies Viral/pharmacology Biochemistry MESH: Protein Structure Tertiary 0302 clinical medicine MESH: Virus Internalization [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Viral Proteins/metabolism Viral Immunology Hypervariable Region 1 chemistry.chemical_classification 0303 health sciences virus diseases Cell Surface Receptor MESH: Viral Hepatitis Vaccines/genetics Hepatitis C 3. Good health [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology 030211 gastroenterology & hepatology Antibody MESH: Hepatitis C/genetics MESH: Viral Proteins/antagonists & inhibitors MESH: Hepatitis C/immunology Viral Hepatitis Vaccines Hepatitis C Virus Viral protein MESH: Viral Proteins/immunology Hepatitis C virus Sciences du Vivant [q-bio]/Médecine humaine et pathologie Biology Microbiology MESH: CD36 Antigens/metabolism 03 medical and health sciences Viral Proteins MESH: Viral Hepatitis Vaccines/immunology Viral entry Cell surface receptor medicine Humans Viral Protein MESH: Hepatitis C/prevention & control Molecular Biology 030304 developmental biology Immune Evasion MESH: Humans Cell Biology Virus Internalization MESH: CD36 Antigens/genetics Virology Antibodies Neutralizing digestive system diseases Hypervariable region Protein Structure Tertiary NS2-3 protease Virus Entry MESH: Viral Proteins/genetics chemistry MESH: Hepacivirus/physiology biology.protein MESH: Antibodies Viral/immunology Glycoprotein |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2012, 287 (42), pp.35631-35645. ⟨10.1074/jbc.M112.382341⟩ Journal of Biological Chemistry, 2012, 287 (42), pp.35631-35645. ⟨10.1074/jbc.M112.382341⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M112.382341⟩ |
| Popis: | High genetic heterogeneity is an important characteristic of hepatitis C virus (HCV) that contributes to its ability to establish persistent infection. The hypervariable region 1 (HVR1) that includes the first 27 amino acid residues of the E2 envelope glycoprotein is the most variable region within the HCV polyprotein. HVR1 plays a major role in both HCV cell entry and immune evasion, but the respective contribution of specific amino acid residues is still unclear. Our mutagenesis analyses of HCV pseudoparticles and cell culture-derived HCV using the H77 isolate indicate that five residues at positions 14, 15, and 25-27 mediate binding of the E2 protein to the scavenger receptor class B, type I receptor, and any residue herein is indispensable for HCV cell entry. The region spanning positions 16-24 contains the sole neutralizing epitope and is dispensable for HCV entry, but it is involved in heparan binding. More importantly, this region is necessary for the enhancement of HCV entry by high density lipoprotein and interferes with virus neutralization by E2-neutralizing antibodies. Residues at positions 1-13 are also dispensable for HCV entry, but they can affect HCV infectivity by modulating binding of the envelope protein to scavenger receptor class B, type I. Mutations occurring at this site may confer resistance to HVR1 antibodies. These findings further our understanding about the mechanisms of HCV cell entry and the significance of HVR1 variation in HCV immune evasion. They have major implications for the development of HCV entry inhibitors and prophylactic vaccines. |
| Databáze: | OpenAIRE |
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