Lili Zhao, Fuwang Chen, Oliver Quitt, Marvin Festag, Marc Ringelhan, Karin Wisskirchen, Julia Festag, Luidmila Yakovleva, Camille Sureau, Felix Bohne, Michaela Aichler, Volker Bruss, Maxim Shevtsov, Maarten van de Klundert, Frank Momburg, Britta S. Möhl, Ulrike Protzer
{"title":"乙型肝炎病毒包膜蛋白可以作为嵌入宿主细胞膜的治疗靶点","authors":"Lili Zhao, Fuwang Chen, Oliver Quitt, Marvin Festag, Marc Ringelhan, Karin Wisskirchen, Julia Festag, Luidmila Yakovleva, Camille Sureau, Felix Bohne, Michaela Aichler, Volker Bruss, Maxim Shevtsov, Maarten van de Klundert, Frank Momburg, Britta S. Möhl, Ulrike Protzer","doi":"10.1111/cmi.13399","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <p>Hepatitis B virus (HBV) infection is a major health threat causing 880,000 deaths each year. Available therapies control viral replication but do not cure HBV, leaving patients at risk to develop hepatocellular carcinoma. Here, we show that HBV envelope proteins (HBs)—besides their integration into endosomal membranes—become embedded in the plasma membrane where they can be targeted by redirected T-cells. HBs was detected on the surface of HBV-infected cells, in livers of mice replicating HBV and in HBV-induced hepatocellular carcinoma. Staining with HBs-specific recombinant antibody MoMab recognising a conformational epitope indicated that membrane-associated HBs remains correctly folded in HBV-replicating cells in cell culture and in livers of HBV-transgenic mice in vivo. MoMab coated onto superparamagnetic iron oxide nanoparticles allowed to detect membrane-associated HBs after HBV infection by electron microscopy in distinct stretches of the hepatocyte plasma membrane. Last but not least, we demonstrate that HBs located on the cell surface allow therapeutic targeting of HBV-positive cells by T-cells either engrafted with a chimeric antigen receptor or redirected by bispecific, T-cell engager antibodies.</p>\n </section>\n \n <section>\n \n <h3> Take Aways</h3>\n \n <div>\n <ul>\n \n <li>HBs become translocated to the plasma membrane.</li>\n \n <li>Novel, recombinant antibody confirmed proper conformation of HBs on the membrane.</li>\n \n <li>HBs provide an interesting target by T-cell-based, potentially curative therapies.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":9844,"journal":{"name":"Cellular Microbiology","volume":"23 12","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2021-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cmi.13399","citationCount":"2","resultStr":"{\"title\":\"Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane\",\"authors\":\"Lili Zhao, Fuwang Chen, Oliver Quitt, Marvin Festag, Marc Ringelhan, Karin Wisskirchen, Julia Festag, Luidmila Yakovleva, Camille Sureau, Felix Bohne, Michaela Aichler, Volker Bruss, Maxim Shevtsov, Maarten van de Klundert, Frank Momburg, Britta S. Möhl, Ulrike Protzer\",\"doi\":\"10.1111/cmi.13399\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <p>Hepatitis B virus (HBV) infection is a major health threat causing 880,000 deaths each year. Available therapies control viral replication but do not cure HBV, leaving patients at risk to develop hepatocellular carcinoma. Here, we show that HBV envelope proteins (HBs)—besides their integration into endosomal membranes—become embedded in the plasma membrane where they can be targeted by redirected T-cells. HBs was detected on the surface of HBV-infected cells, in livers of mice replicating HBV and in HBV-induced hepatocellular carcinoma. Staining with HBs-specific recombinant antibody MoMab recognising a conformational epitope indicated that membrane-associated HBs remains correctly folded in HBV-replicating cells in cell culture and in livers of HBV-transgenic mice in vivo. MoMab coated onto superparamagnetic iron oxide nanoparticles allowed to detect membrane-associated HBs after HBV infection by electron microscopy in distinct stretches of the hepatocyte plasma membrane. Last but not least, we demonstrate that HBs located on the cell surface allow therapeutic targeting of HBV-positive cells by T-cells either engrafted with a chimeric antigen receptor or redirected by bispecific, T-cell engager antibodies.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Take Aways</h3>\\n \\n <div>\\n <ul>\\n \\n <li>HBs become translocated to the plasma membrane.</li>\\n \\n <li>Novel, recombinant antibody confirmed proper conformation of HBs on the membrane.</li>\\n \\n <li>HBs provide an interesting target by T-cell-based, potentially curative therapies.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":9844,\"journal\":{\"name\":\"Cellular Microbiology\",\"volume\":\"23 12\",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2021-11-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cmi.13399\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular Microbiology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cmi.13399\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Microbiology","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cmi.13399","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane
Hepatitis B virus (HBV) infection is a major health threat causing 880,000 deaths each year. Available therapies control viral replication but do not cure HBV, leaving patients at risk to develop hepatocellular carcinoma. Here, we show that HBV envelope proteins (HBs)—besides their integration into endosomal membranes—become embedded in the plasma membrane where they can be targeted by redirected T-cells. HBs was detected on the surface of HBV-infected cells, in livers of mice replicating HBV and in HBV-induced hepatocellular carcinoma. Staining with HBs-specific recombinant antibody MoMab recognising a conformational epitope indicated that membrane-associated HBs remains correctly folded in HBV-replicating cells in cell culture and in livers of HBV-transgenic mice in vivo. MoMab coated onto superparamagnetic iron oxide nanoparticles allowed to detect membrane-associated HBs after HBV infection by electron microscopy in distinct stretches of the hepatocyte plasma membrane. Last but not least, we demonstrate that HBs located on the cell surface allow therapeutic targeting of HBV-positive cells by T-cells either engrafted with a chimeric antigen receptor or redirected by bispecific, T-cell engager antibodies.
Take Aways
HBs become translocated to the plasma membrane.
Novel, recombinant antibody confirmed proper conformation of HBs on the membrane.
HBs provide an interesting target by T-cell-based, potentially curative therapies.
期刊介绍:
Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.