Hepatitis B Virus (HBV) Surface Antigen Interacts with and Promotes Cyclophilin A Secretion: Possible Link to Pathogenesis of HBV Infection

被引:69
作者
Tian, Xiaochen [1 ]
Zhao, Chao [1 ,2 ]
Zhu, Hongguang [2 ,3 ]
She, Weimin [4 ]
Zhang, Jiming [5 ]
Liu, Jing [1 ,2 ]
Li, Lanjuan [6 ]
Zheng, Shusen [6 ]
Wen, Yu-Mei [1 ,2 ]
Xie, Youhua [1 ,2 ]
机构
[1] Fudan Univ, Key Lab Med Mol Virol, Shanghai Med Coll, Shanghai 200433, Peoples R China
[2] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China
[3] Fudan Univ, Dept Pathol, Shanghai Med Coll, Shanghai 200433, Peoples R China
[4] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China
[5] Fudan Univ, Huashan Hosp, Shanghai 200433, Peoples R China
[6] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Hangzhou 310003, Zhejiang, Peoples R China
关键词
TARGET; CELLS; GENE; PARTICLES; MATRIX; HIV-1; DNA; IDENTIFICATION; REPLICATION; CALCINEURIN;
D O I
10.1128/JVI.02555-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Cyclophilin A (CypA), predominantly located intracellularly, is a multifunctional protein. We previously reported decreased CypA levels in hepatocytes of transgenic mice expressing hepatitis B virus (HBV) surface antigen (HBsAg). In this study, we found that expression of HBV small surface protein (SHBs) in human hepatoma cell lines specifically triggered CypA secretion, whereas SHBs added extracellularly to culture medium did not. Moreover, CypA secretion was not promoted by the expression of a secretion deficient SHBs mutant, suggesting a close association between secretion of CypA and SHBs. Interaction between CypA and SHBs was observed by using coimmunoprecipitation and glutathione S-transferase pull-down assays. Hydrodynamic injection of the SHBs expression construct into C57BL/6J mice resulted in increased serum CypA levels and ALT/AST levels, as well as the infiltration of inflammatory cells surrounding SHBs-positive hepatocytes. The inflammatory response and serum ALT/AST level were reduced when the chemotactic effect of CypA was inhibited by cyclosporine and anti-CD147 antibody. Furthermore, higher serum CypA levels were detected in chronic hepatitis B patients than in healthy individuals. In HBV patients who had received liver transplantation, serum CypA levels declined dramatically after the loss of HBsAg as a consequence of liver transplantation. Taken together, these results indicate that expression and secretion of SHBs can promote CypA secretion, which may contribute to the pathogenesis of HBV infection.
引用
收藏
页码:3373 / 3381
页数:9
相关论文
共 50 条
  • [21] Impact of Hepatitis B Virus (HBV) X Gene Mutations on Hepatocellular Carcinoma Development in Chronic HBV Infection
    Lee, Jong-Han
    Han, Kwang-Hyub
    Lee, Jae Myun
    Park, Jeon Han
    Kim, Hyon-Suk
    CLINICAL AND VACCINE IMMUNOLOGY, 2011, 18 (06) : 914 - 921
  • [22] Secreted hepatitis B virus splice variants differ by HBV genotype and across phases of chronic hepatitis B infection
    Maslac, Olivia
    Wagner, Josef
    Sozzi, Vitina
    Mason, Hugh
    Svarovskaia, Jenny
    Tan, Susanna
    Gaggar, Anuj
    Locarnini, Stephen
    Yuen, Lilly
    Littlejohn, Margaret
    Revill, Peter A.
    JOURNAL OF VIRAL HEPATITIS, 2022, 29 (08) : 604 - 615
  • [23] Alisporivir Inhibition of Hepatocyte Cyclophilins Reduces HBV Replication and Hepatitis B Surface Antigen Production
    Phillips, Sandra
    Chokshi, Shilpa
    Chatterji, Udayan
    Riva, Antonio
    Bobardt, Michael
    Williams, Roger
    Gallay, Philippe
    Naoumov, Nikolai V.
    GASTROENTEROLOGY, 2015, 148 (02) : 403 - U219
  • [24] Impact of hepatitis B virus genotypes and surface antigen variants on the performance of HBV real time PCR quantification
    Thibault, Vincent
    Laperche, Syria
    Akhavan, Sepideh
    Servant-Delmas, Annabelle
    Belkhiri, Dalila
    Roque-Afonso, Anne-Marie
    JOURNAL OF VIROLOGICAL METHODS, 2009, 159 (02) : 265 - 270
  • [25] Modulators of HBV capsid assembly as an approach to treating hepatitis B virus infection
    Cole, Andrew G.
    CURRENT OPINION IN PHARMACOLOGY, 2016, 30 : 131 - 137
  • [26] Metabolic Regulation of Hepatitis B Virus Infection in HBV-Transgenic Mice
    Lan, Wenning
    Wang, Yang
    Zhou, Zixiong
    Sun, Xia
    Zhang, Yun
    Zhang, Fangrong
    METABOLITES, 2022, 12 (04)
  • [27] Circulating HBV RNA and Hepatitis B Core-Related Antigen Trajectories in Persons With HIV/HBV Coinfection and Hepatitis B Surface Antigen Loss During Tenofovir Therapy
    Begre, Lorin
    Boyd, Anders
    Plissonnier, Marie-Laure
    Testoni, Barbara
    Salazar-Vizcaya, Luisa
    Suter-Riniker, Franziska
    Scholtes, Caroline
    Beguelin, Charles
    Rockstroh, Jurgen K.
    Gunthard, Huldrych F.
    Calmy, Alexandra
    Cavassini, Matthias
    Hirsch, Hans H.
    Schmid, Patrick
    Bernasconi, Enos
    Levrero, Massimo
    Wandeler, Gilles
    Zoulim, Fabien
    Rauch, Andri
    JOURNAL OF INFECTIOUS DISEASES, 2024, 230 (04) : e954 - e963
  • [28] Viral Adaptation to Host Immune Responses Occurs in Chronic Hepatitis B Virus (HBV) Infection, and Adaptation Is Greatest in HBV e Antigen-Negative Disease
    Desmond, Christopher P.
    Gaudieri, Silvana
    James, Ian R.
    Pfafferott, Katja
    Chopra, Abha
    Lau, George K.
    Audsley, Jennifer
    Day, Caroline
    Chivers, Sarah
    Gordon, Adam
    Revill, Peter A.
    Bowden, Scott
    Ayres, Anna
    Desmond, Paul V.
    Thompson, Alexander J.
    Roberts, Stuart K.
    Locarnini, Stephen A.
    Mallal, Simon A.
    Lewin, Sharon R.
    JOURNAL OF VIROLOGY, 2012, 86 (02) : 1181 - 1192
  • [29] Efficient Inhibition of Hepatitis B Virus (HBV) Replication and cccDNA Formation by HBV Ribonuclease H Inhibitors during Infection
    Chauhan, Ranjit
    Li, Qilan
    Woodson, Molly E.
    Gasonoo, Makafui
    Meyers, Marvin J.
    Tavis, John E.
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2021, 65 (12)
  • [30] An Overview of Hepatitis B Virus Surface Antigen Secretion Inhibitors
    Mohebbi, Alireza
    Lorestani, Nazanin
    Tahamtan, Alireza
    Kargar, Niki L.
    Tabarraei, Alijan
    FRONTIERS IN MICROBIOLOGY, 2018, 9