Review
Microbiology
Rui Gui, Quanjiao Chen
Summary: Cell death plays a dual role in viral infections, with moderate death serving as a protective response and excessive death leading to tissue destruction and mortality. Influenza A virus infection can cause uncontrolled hyper-inflammatory reactions and serious illnesses. Understanding the mechanisms of cell death induced by the virus could aid in the development of better antiviral treatments.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Xuqiu Lei, Yongzhi Chen, Egil Lien, Katherine A. Fitzgerald
Summary: Influenza A virus (IAV) induces multiple types of cell death, including necroptosis, apoptosis, and pyroptosis. MLKL promotes inflammasome activation and IL-1 beta processing in IAV-infected macrophages, while caspase-8 coordinates the maturation and secretion of IL-1 beta in the absence of the MLKL-inflammasome axis. MLKL and caspase-8 serve as redundant mechanisms for inflammatory cell death in response to IAV infection.
Article
Multidisciplinary Sciences
Vijaykrishna Dhanasekaran, Sheena Sullivan, Kimberly M. Edwards, Ruopeng Xie, Arseniy Khvorov, Sophie A. Valkenburg, Benjamin J. Cowling, Ian G. Barr
Summary: Since the onset of the COVID-19 pandemic, public health measures and travel restrictions have heavily suppressed global influenza circulation. The genetic diversity of seasonal influenza viruses has significantly decreased, with the influenza B/Yamagata lineage not conclusively detected. Travel restrictions have confined the circulation of different influenza viruses to specific regions, leading to a continuous decline in global transmission of seasonal influenza, except in select hotspots that may seed future epidemics. Additionally, the selection of influenza vaccine strains and epidemic control face challenges due to waning population immunity and sporadic case detection.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Ningbo Zheng, Jing Fang, Gang Xue, Ziyu Wang, Xiaoyin Li, Mengshi Zhou, Guangxu Jin, Masmudur M. Rahman, Grant McFadden, Yong Lu
Summary: In this study, tumor-specific T cells infected with myxoma virus were used to deliver the virus into solid tumors, overcoming primary resistance. In addition to inducing classic tumor cell apoptosis and pyroptosis, these infected T cells were found to induce a special type of cell death called tumor cell autosis, which helps to restrain tumor antigen escape.
Review
Biochemistry & Molecular Biology
Chuyuan Zhang, Xinjie Meng, Hanjun Zhao
Summary: Virus-cell fusion plays a crucial role in viral infection and understanding this process is important for developing antiviral drugs. This review focuses on the fusion of influenza virus and SARS-CoV-2 with host cells, comparing their differences and discussing the development of drugs to prevent respiratory virus infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hongya Ning, Shih-Hsin Chiu, Xiaodong Xu, Yanmei Ma, Ji-Long Chen, Guihong Yang
Summary: The expression of PD-L1 was significantly upregulated in cells infected with H1N1 influenza A virus. PD-L1 overexpression promoted viral replication and downregulated type-I and type-III interferons and interferon-stimulated genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Rui Gui, Huabin Zheng, Liping Ma, Renyi Liu, Xian Lin, Xianliang Ke, Chang Ye, Xiaoqin Jian, Quanjiao Chen
Summary: This study reveals for the first time the molecular mechanisms of cell death during influenza A virus infection and identifies a novel component, SPAG9. The findings have important implications for expanding our understanding of cell death mechanisms.
Article
Immunology
Ying Liu, Xun Song, Chenyang Li, Hao Hu, Wanlin Li, Lu Wang, Jing Hu, Chenghui Liao, Hanbai Liang, Zhendan He, Liang Ye
Summary: Chrysin has been found to inhibit H1N1 influenza virus replication by blocking cell cycle and apoptosis mechanisms, potentially aiding in limiting the spread of respiratory viruses.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Microbiology
Sharath Basavaraju, Sanchita Mishra, Rashi Jindal, Sannula Kesavardhana
Summary: Influenza viruses cause respiratory tract infections and global pandemics by transmitting from animals to humans. Innate immune response to IAV infection promotes cell death and inflammatory reactions to defend against the virus. Dysregulated cell death and excessive inflammation contribute to immunopathology in severe infections. ZBP1/DAI and RIPK3 play essential roles in apoptosis, necroptosis, and pyroptosis during IAV infection, affecting host defense and pathogenicity.
Article
Immunology
Hannah L. Wallace, Lingyan Wang, Cassandra L. Gardner, Christopher P. Corkum, Michael D. Grant, Kensuke Hirasawa, Rodney S. Russell
Summary: This study investigated the mechanism of HCV-induced cell death, revealing that pyroptosis occurs earlier than apoptosis during infection. Knockout of NLRP3 and gasdermin-D affected HCV-induced pyroptosis, and there may be crosstalk between caspase-3 and pyroptosis initiation in the context of HCV infection. Lower viral titres and increased intracellular virus levels were observed in knockout Huh-7.5 cells, suggesting HCV may induce programmed cell death to enhance virus release. These results contribute to understanding HCV pathogenesis and suggest various programmed cell death pathways are not mutually exclusive.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Microbiology
Fanhua Wei, Chengjiang Gao, Yujiong Wang
Summary: Influenza virus infection can lead to cytokine storms, contributing to severe outcomes. Immunomodulatory drugs offer a promising approach for treating hypercytokinemia induced by acute viral infections.
CRITICAL REVIEWS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mallory L. Myers, John R. Gallagher, Alexander J. Kim, Walker H. Payne, Samantha Maldonado-Puga, Haralabos Assimakopoulos, Kevin W. Bock, Udana Torian, Ian N. Moore, Audray K. Harris
Summary: Influenza viruses cause worldwide epidemics and yearly reformulation of commercial influenza vaccines (CIV) due to the antigenic variation of Hemagglutinin (HA). This study investigates the structural organization of HA in four current CIVs using electron microscopy, revealing different arrangements including individual HAs, starfish structures, and spiked-nanodisc structures. CIVs with spiked nanodiscs induce the highest levels of cross-reactive antibodies. Therefore, HA structural organization can be an important parameter for CIVs and their efficacy.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Hae-Ji Kang, Ki-Back Chu, Keon-Woong Yoon, Gi-Deok Eom, Jie Mao, Fu-Shi Quan
Summary: This study demonstrates that influenza B virus-like particle vaccines expressing hemagglutinin, neuraminidase, or both antigens can provide cross-protections against mismatched Victoria lineage virus infections, by inducing antibody and T cell responses to reduce lung viral loads and minimize infection outcomes.
Article
Virology
Pinar Yazici ozkaya, Ese Eda Turanli, Hamdi Metin, Ayca Aydin Uysal, Candan cicek, Bulent Karapinar
Summary: This study aimed to identify the clinical features and mortality associated with severe influenza A and B virus infections in children admitted to the pediatric intensive care unit (PICU) between 2012 and 2019. The study found that although the proportion of influenza A cases admitted to the PICU was higher, the percentage of cases requiring PICU admission was nearly two times higher in influenza B cases. Additionally, there was no statistically significant difference in disease severity and complications in patients with influenza A and influenza B.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Immunology
Xiaoyuan Bai, Wenxian Yang, Heqiao Li, Yuna Zhao, Wenhui Fan, He Zhang, Wenjun Liu, Lei Sun
Summary: CsA regulates macrophage polarization and attenuates influenza virus-induced inflammatory responses by decreasing pro-inflammatory cytokines expression, increasing anti-inflammatory cytokines expression, and altering the polarization of macrophages from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. These effects depend on the binding of CsA to CypA.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jieru Deng, Chunni Lu, Chuanxin Liu, Sara Oveissi, W. Douglas Fairlie, Erinna F. Lee, Pamuk Bilsel, Hamsa Puthalakath, Weisan Chen
Summary: The study demonstrates that IAV infection induces endogenous presentation of a viral epitope by MHC-II to CD4(+) T cells, dependent on de novo protein synthesis and the ER-Golgi network. Some antigenic peptides are of cytosolic origin in this process. Additionally, autophagy inhibitors and deletion of autophagy-related genes block most of the MHC-II-restricted endogenous IAV antigen presentation.
Article
Biochemical Research Methods
Thanh Kha Phan, Pamali Fonseka, Rochelle Tixeira, Mohashin Pathan, Ching-Seng Ang, Dilara Ceyda Ozkocak, Suresh Mathivanan, Ivan Ka Ho Poon
Summary: Apoptotic bodies (ApoBDs) are large extracellular vesicles released exclusively by apoptotic cells, possessing therapeutically exploitable properties. The PANX1 channel has been identified as a key regulator of ApoBD formation, influencing both nuclear content packaging and ApoBD size. Pharmacologically targeting PANX1 activity may enhance the therapeutic potential of ApoBD-based therapies.
Article
Cell Biology
Natalie J. Bitto, Lesley Cheng, Ella L. Johnston, Rishi Pathirana, Thanh Kha Phan, Ivan K. H. Poon, Neil M. O'Brien-Simpson, Andrew F. Hill, Timothy P. Stinear, Maria Kaparakis-Liaskos
Summary: Gram-positive bacteria produce membrane vesicles (MVs) containing microbe-associated molecular patterns (MAMPs) such as proteins, nucleic acids, and peptidoglycan, which can activate pattern recognition receptors (PRRs) in host epithelial cells and promote cytokine and chemokine release. Additionally, MVs can be degraded intracellularly through autophagy, enhancing our understanding of their immunostimulatory roles and fate within the host.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Article
Immunology
Christopher B. Medina, Yu-Hsin Chiu, Marta E. Stremska, Christopher D. Lucas, Ivan Poon, Kenneth S. Tung, Michael R. Elliott, Bimal Desai, Ulrike M. Lorenz, Douglas A. Bayliss, Kodi S. Ravichandran
Summary: The nucleotide release channel Panx1 plays an immunoregulatory role in T cell crosstalk during allergic airway inflammation, aiding in the suppression of disease progression. Mechanistic studies have shown the importance of Panx1-dependent Treg:Teff cell communication in restricting airway disease.
Article
Cell Biology
Chunni Lu, Weisan Chen
Summary: This study tracked different types of Treg cells in mice infected with influenza virus, finding that Foxp3(+)Helios(+) Tregs were mainly enriched in the lungs and lymph nodes, and these cells accumulated more rapidly during secondary infection with stronger suppressive function.
IMMUNOLOGY AND CELL BIOLOGY
(2021)
Article
Virology
Miaojuan Huang, Rong Xu, Cristina Triffon, Nicole Mifsud, Weisan Chen
Summary: This study reveals a broad CD8(+) T cell response in a healthy individual to IAV infection, contrary to the typical immunodominance hierarchy. Through systematic antigen screening and epitope prediction, novel minimal epitope sequences for nine IAV proteins were identified, restricted to specific HLA alleles. These novel epitopes are highly conserved among different IAV strains and geographic locations.
Article
Multidisciplinary Sciences
E. A. Monson, K. M. Crosse, M. Duan, W. Chen, R. D. O'Shea, L. M. Wakim, J. M. Carr, D. R. Whelan, K. J. Helbig
Summary: Lipid droplets (LDs) are critical in enhancing modulation of IFN, controlling viral replication, and facilitating early antiviral immune response, marking a paradigm shift in understanding the molecular mechanisms of effective antiviral responses.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Monisha Samuel, Pamali Fonseka, Rahul Sanwlani, Lahiru Gangoda, Sing Ho Chee, Shivakumar Keerthikumar, Alex Spurling, Sai V. Chitti, Damien Zanker, Ching-Seng Ang, Ishara Atukorala, Taeyoung Kang, Sanjay Shahi, Akbar L. Marzan, Christina Nedeva, Claire Vennin, Morghan C. Lucas, Lesley Cheng, David Herrmann, Mohashin Pathan, David Chisanga, Sean C. Warren, Kening Zhao, Nidhi Abraham, Sushma Anand, Stephanie Boukouris, Christopher G. Adda, Lanzhou Jiang, Tanmay M. Shekhar, Nikola Baschuk, Christine J. Hawkins, Amelia J. Johnston, Jacqueline Monique Orian, Nicholas J. Hoogenraad, Ivan K. Poon, Andrew F. Hill, Markandeya Jois, Paul Timpson, Belinda S. Parker, Suresh Mathivanan
Summary: The study demonstrates that extracellular vesicles from milk can be absorbed in mice and detected in multiple organs. Orally administered milk-derived extracellular vesicles have a context specific role in promoting or suppressing primary tumor growth and metastasis in mouse models.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Cell Biology
Mary Speir, Amy H. Chan, Daniel S. Simpson, Tashbib Khan, Tahnee L. Saunders, Ivan K. H. Poon, Georgia K. Atkin-Smith
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Review
Cell Biology
Amy L. Hodge, Amy A. Baxter, Ivan K. H. Poon
Summary: Dendritic cells release extracellular vesicles containing functional molecules that play important roles in immune responses and diseases, and are being explored as potential immunotherapeutic agents.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Guneet K. Bindra, Scott A. Williams, Fung T. Lay, Amy A. Baxter, Ivan K. H. Poon, Mark D. Hulett, Thanh Kha Phan
Summary: Defensins are a crucial component of the cationic host defence peptide (HDP) family and have antimicrobial and immunomodulatory activities. This study reveals that human beta-defensin 2 (HBD-2) can kill tumor cells through acute lytic cell death and does not affect tumor cell migration.
Article
Microbiology
Jennifer Habel, Andrea Nguyen, Louise Rowntree, Christopher Szeto, Nicole Mifsud, E. Bridie Clemens, Liyen Loh, Weisan Chen, Steve Rockman, Jane W. Nelson, Jane Davies, Adrian Miller, Steven Y. C. T. Tong, Jamie Rossjohn, Stephanie M. Gras, Anthony Purcell, Luca M. Hensen, Katherine Kedzierska, Patricia M. Illing
Summary: HLA-A*11:01 is highly prevalent in East Asian and Oceanian populations and is associated with high risk of severe influenza disease. Using immunopeptidomics, researchers identified novel CD8(+) T cell targets for influenza A and influenza B viruses in HLA-A*11:01-expressing individuals. These findings have implications for the design of broadly cross-reactive influenza vaccines.
Article
Biochemistry & Molecular Biology
Xia Yang, Hailiang Sun, Zhening Zhang, Weixin Ou, Fengxiang Xu, Ling Luo, Yahong Liu, Weisan Chen, Jianxin Chen
Summary: Influenza A virus (IAV) infections pose a serious threat to public health and there is an urgent need for novel anti-IAV medications. This study reveals that ginsenoside rk1 (G-rk1) and G-rg5, derived from panax ginseng, exhibit significant antiviral effects against different IAV subtypes both in vitro and in vivo. G-rk1 specifically blocks IAV binding to sialic acid and interacts with HA1, making it a potential approach for preventing and treating IAV infections.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Scott A. Williams, Fung T. Lay, Guneet K. Bindra, Suresh Banjara, Ivan K. H. Poon, Thanh Kha Phan, Marc Kvansakul, Mark D. Hulett
Summary: The authors report the structure of saltwater crocodile defensin CpoBD13 and its pH-dependent antifungal activity.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Xia Yang, Feixiang Long, Weixin Jia, Mingxin Zhang, Guanming Su, Ming Liao, Zhenling Zeng, Weisan Chen, Jianxin Chen
Summary: We demonstrated that artemisinin and its derivative artesunate (AS) have broad antiviral activity against H5N1, H1N1, H3N2, and oseltamivir-resistant influenza A virus in vitro. AS treatment significantly protected mice from lethal challenges with H1N1 and H5N1 IAV, and the combination of AS and peramivir showed improved survival outcomes compared to monotherapy. Mechanistically, AS inhibited PDE4, induced cAMP accumulation, reduced ERK phosphorylation, and blocked IAV vRNP export, thus suppressing IAV replication.
ANTIVIRAL RESEARCH
(2023)