Journal of Microbiology

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Recombinant Protein Mimicking the Antigenic Structure of the Viral Surface Envelope Protein Reinforces Induction of an Antigen‑Specific and Virus‑Neutralizing Immune Response Against Dengue Virus: Ju Kim , Tae Young Lim , Jisang Park , Yong&#; J. Microbiol. 2023;61(1):131-143. Published online February 1, 2023; DOI: https://doi.org/10.1007/s12275-023-00021-z

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Dengue virus (DENV), belonging to the family Flaviviridae, is the causative agent of dengue and comprises four serotypes. A second heterologous DENV infection is a critical risk factor for severe dengue, and no effective vaccine is available to prevent infection by all four DENV serotypes. Recombinant DENV vaccines are primarily based on the envelope proteins, prM and E. The E protein and its envelope domain III (EDIII) have been investigated as candidate antigens (Ags) for recombinant subunit vaccines. However, most EDIII-based Ags are monomers that do not display the cognate antigenic structure of E protein, which is essential for induction of virus-neutralizing immunity. Here, we developed recombinant DENV-2 envelope domain (r2ED) protein as an Ag that mimics the quaternary structure of E protein on the DENV surface. We confirmed that r2ED retained the conformational epitope displayed at the E-dimer interface, which reportedly exhibits broad virus-neutralizing capacity, without displaying the fusion loop epitope that causes antibody (Ab)-dependent enhancement. Furthermore, compared with EDIII alone, r2ED elicited stronger Ag-specific and cross-reactive neutralizing Ab and T cell-mediated immune responses in mice. This Ag-specific immunity was maintained at an elevated level 6 months after the last immunization, suggesting sustained Ag-specific immune memory. Taken together, these observations suggest that r2ED could be used to develop an improved subunit vaccine capable of inducing a broadly cross-reactive and long-lasting immune response against DENV infection.

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Peptides of a Feather: How Computation Is Taking Peptide Therapeutics under Its Wing
Thomas David Daniel Kazmirchuk, Calvin Bradbury-Jost, Taylor Ann Withey, Tadesse Gessese, Taha Azad, Bahram Samanfar, Frank Dehne, Ashkan Golshani
Genes.2023; 14(6): 1194. CrossRef

Regulation of HBV-specific CD8+ T cell-mediated inflammation is diversified in different clinical presentations of HBV infection: Colin M. Dinney , Lu-Dong Zhao , Charles D. Conrad , Jay M. Duker , Richard O. Karas , Zhibin Hu , Michele A. Hamilton , Thomas R. Gillis , Thomas M. Parker , Bing Fan , Andrew H. Advani , Fred B. Poordad , Paulette L. Fauceglia , Kathrin M. Kirsch , Peter T. Munk , Marc P. Ladanyi , Bernard A. Bochner , Justin A. Bekelman , Carla M. Grandori , James C. Olson , Ronald D. Lechan , Ghassan M.A. Abou , Mark A. Goodarzi; J. Microbiol. 2015;53(10):718-724. Published online October 2, 2015; DOI: https://doi.org/10.1007/s12275-015-5314-y

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Abstract

Chronic HBV infection is the leading cause of liver cirrhosis and hepatic cancer, but the individual responses toward HBV infection are highly variable, ranging from asymptomatic to chronic active hepatitis B inflammation. In this study, we hypothesized that the different individual responses to HBV infection was associated with differences in HBV-specific CD8+ T cell-mediated inflammation and cytotoxicity. Blood samples were collected from subjects with asymptomatic HBV-infection, subjects undergoing active chronic HBV flares (active CHB), and subjects with HBV-infected hepatocellular carcinoma (HBV-HCC). By tetramer staining, we found that all three groups had similar frequencies of HBVspecific CD8+ T cells. However, after HBV peptide stimulation, the HBV-specific CD8+ T cells in asymptomatic subjects had significantly stronger interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and CD107a expression than those in active CHB and HBV-HCC patients. Examination of surface marker expression revealed that the PD-1-Tim-3- double-negative cell population was the main contributor to HBV-specific inflammation. In active CHB patients and HBV-HCC patients, however, the frequencies of activated PD-1-Tim-3- cells were significantly reduced. Moreover, the serum HBV DNA titer was not correlated with the frequencies of HBV-specific CD8+ T cells but was inversely correlated with the frequencies of IFN-g-expressing and CD107a-express cells in response to HBV stimulation. Together, our data demonstrated that the status of HBVspecific CD8+ T cell exhaustion was associated with different clinical outcomes of chronic HBV infection.

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The Adaptive Immune Response in Hepatitis B Virus-Associated Hepatocellular Carcinoma Is Characterized by Dysfunctional and Exhausted HBV-Specific T Cells
Malene Broholm, Anne-Sofie Mathiasen, Ása Didriksen Apol, Nina Weis
Viruses.2024; 16(5): 707. CrossRef
Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC
Muhammad Naveed Khan, Binli Mao, Juan Hu, Mengjia Shi, Shunyao Wang, Adeel Ur Rehman, Xiaosong Li
Frontiers in Immunology.2024;[Epub] CrossRef
The CD8+ T cell exhaustion mechanisms in chronic hepatitis B infection and immunotherapeutic strategies: a systematic review
Esmaeil Allahmoradi, Ramtin Mohammadi, Peyman Kheirandish Zarandi, Seyed Moayed Alavian, Mohammad Heiat
Expert Review of Clinical Immunology.2023; 19(6): 671. CrossRef
Increase in Serum Soluble Tim-3 Level Is Related to the Progression of Diseases After Hepatitis Virus Infection
Lingli Chen, Xiaomei Yu, Chunyan Lv, Yaping Dai, Tao Wang, Shaoxiong Zheng, Yuan Qin, Xiumei Zhou, Yigang Wang, Hao Pei, Hongming Fang, Biao Huang
Frontiers in Medicine.2022;[Epub] CrossRef
Programmed death 1 expressing CD8+CXCR5+ follicular T cells constitute effector rather than exhaustive phenotype in patients with chronic hepatitis B
Arshi Khanam, Lydia S. Y. Tang, Shyam Kottilil
Hepatology.2022; 75(3): 690. CrossRef
Insights into the Relationship between Pentraxin-3 and Cancer
Maria Bogdan, Andreea-Daniela Meca, Adina Turcu-Stiolica, Carmen Nicoleta Oancea, Roxana Kostici, Marin Valeriu Surlin, Cristina Florescu
International Journal of Molecular Sciences.2022; 23(23): 15302. CrossRef
Hepatitis B Flare in Hepatitis B e Antigen-Negative Patients: A Complicated Cascade of Innate and Adaptive Immune Responses
Ming-Ling Chang, Yun-Fan Liaw
International Journal of Molecular Sciences.2022; 23(3): 1552. CrossRef
Soluble programmed cell death-1 predicts hepatocellular carcinoma development during nucleoside analogue treatment
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Scientific Reports.2022;[Epub] CrossRef
The Value of Immune System in the Progression of Chronic Hepatitis B
甜甜武
Advances in Clinical Medicine.2021; 11(11): 5386. CrossRef
Identification of the association between HBcAg-specific T cell and viral control in chronic HBV infection using a cultured ELISPOT assay
Chengcong Chen, Xiaotao Jiang, Xuan Liu, Ling Guo, Weibin Wang, Shuqin Gu, Chunhua Wen, Xuan Yi, Libo Tang, Yongyin Li
Journal of Leukocyte Biology.2021; 109(2): 455. CrossRef
Molecular signature of hepatitis B virus regulation by interferon‐γ in primary human hepatocytes
Takuto Nosaka, Tatsushi Naito, Hidetaka Matsuda, Masahiro Ohtani, Katsushi Hiramatsu, Tomoyuki Nemoto, Tsutomu Nishizawa, Hiroaki Okamoto, Yasunari Nakamoto
Hepatology Research.2020; 50(3): 292. CrossRef
Serum pentraxin 3 as a biomarker of hepatocellular carcinoma in chronic hepatitis B virus infection
Huan Deng, Xiude Fan, Xiaoyun Wang, Lu Zeng, Kun Zhang, Xiaoge Zhang, Na Li, Qunying Han, Yi Lv, Zhengwen Liu
Scientific Reports.2020;[Epub] CrossRef
Immune Checkpoints in Viral Infections
Huiming Cai, Ge Liu, Jianfeng Zhong, Kai Zheng, Haitao Xiao, Chenyang Li, Xun Song, Ying Li, Chenshu Xu, Haiqiang Wu, Zhendan He, Qinchang Zhu
Viruses.2020; 12(9): 1051. CrossRef
PRDM1 levels are associated with clinical diseases in chronic HBV infection and survival of patients with HBV-related hepatocellular carcinoma
Na Li, Xiude Fan, Xiaoyun Wang, Huan Deng, Kun Zhang, Xiaoge Zhang, Ye Wang, Qunying Han, Yi Lv, Zhengwen Liu
International Immunopharmacology.2019; 73: 156. CrossRef
Hepatitis B virus-specific effector CD8+ T cells are an important determinant of disease prognosis: A meta-analysis
Juzeng Zheng, Zhanfan Ou, Yilun Xu, Ziqiang Xia, Xianfan Lin, Sisi Jin, Yang Liu, Jinming Wu
Vaccine.2019; 37(18): 2439. CrossRef
PRDM1 rs1010273 polymorphism is associated with overall survival of patients with hepatitis B virus-related hepatocellular carcinoma
Na Li, Xiude Fan, Xiaoyun Wang, Huan Deng, Kun Zhang, Xiaoge Zhang, Qunying Han, Yi Lv, Zhengwen Liu
Immunology Letters.2019; 213: 39. CrossRef
Association of viral hepatitis and bipolar disorder: a nationwide population-based study
Lee-Won Chong, Chih-Chao Hsu, Chang-Yin Lee, Ruey-Hwang Chou, Cheng-Li Lin, Kuang-Hsi Chang, Yi-Chao Hsu
Journal of Translational Medicine.2018;[Epub] CrossRef
Tim-3 expression and its role in hepatocellular carcinoma
Feifei Liu, Yanning Liu, Zhi Chen
Journal of Hematology & Oncology.2018;[Epub] CrossRef
Novel Immunotherapy Strategies for Hepatobiliary Cancers
Thomas T DeLeon, Yumei Zhou, Bolni M Nagalo, Raquel T Yokoda, Daniel H Ahn, Ramesh K Ramanathan, Marcela A Salomao, Bashar A Aqel, Amit Mahipal, Tanios S Bekaii-Saab, Mitesh J Borad
Immunotherapy.2018; 10(12): 1077. CrossRef
Association of LTBR polymorphisms with chronic hepatitis B virus infection and hepatitis B virus-related hepatocellular carcinoma
Qianqian Zhu, Na Li, Fang Li, Jiao Sang, Huan Deng, Qunying Han, Yi Lv, Chunyan Li, Zhengwen Liu
International Immunopharmacology.2017; 49: 126. CrossRef
The development of hepatocarcinoma after long-term antivirus treatment of Chinese patients with chronic hepatitis B virus infection: Incidence, long-term outcomes and predictive factors
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Clinics and Research in Hepatology and Gastroenterology.2017; 41(3): 311. CrossRef
Impaired Subset Progression and Polyfunctionality of T Cells in Mice Exposed to Methamphetamine during Chronic LCMV Infection
Uma Sriram, Beth L. Hill, Jonathan M. Cenna, Larisa Gofman, Nicole C. Fernandes, Bijayesh Haldar, Raghava Potula, Anil Kumar
PLOS ONE.2016; 11(10): e0164966. CrossRef

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