Article
Virology
Jiangwei Song, Yitong Guo, Dan Wang, Rong Quan, Jing Wang, Jue Liu
Summary: The Seneca Valley virus (SVV) inhibits the type I interferon (IFN) response by degrading STAT1, STAT2, and IRF9, and cleaving STAT2, which leads to impaired IFN-stimulated gene activity. Additionally, SVV blocks the nuclear import of STAT1 and STAT2 by degrading karyopherin 1, thereby evading the host immune response.
JOURNAL OF VIROLOGY
(2023)
Review
Immunology
Christopher James Arthur Duncan, Sophie Hambleton
Summary: STAT2 is unique among the STAT family members in its involvement exclusively in type I and III interferon signaling pathways, acting as both a positive and negative regulator of IFN-I signaling. Opposing functions of STAT2 in monogenic diseases are evident, with autosomal recessive STAT2 deficiency leading to heightened susceptibility to severe viral diseases and homozygous missense substitutions causing severe type I interferonopathy.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Kensei Kishimoto, Catera L. Wilder, Justin Buchanan, Minh Nguyen, Chidera Okeke, Alexander Hoffmann, Quen J. Cheng
Summary: IFN-beta signaling can activate both ISGF3 and GAF in murine lung epithelial cells, with GAF potentially acting as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Xiangjie Chen, Qian Zhao, Ying Xu, Qiuyu Wu, Renxia Zhang, Qian Du, Ying Miao, Yibo Zuo, Hong-Guang Zhang, Fan Huang, Tengfei Ren, Jiuyi He, Caixia Qiao, Yue Li, Shifeng Li, Yang Xu, Depei Wu, Zhengyuan Yu, Haitao Lv, Jun Wang, Hui Zheng, Yukang Yuan
Summary: This study reveals a regulatory mechanism of IFNAR2 ubiquitination and protein stability in IFN-I signaling, which is mediated by MID1. MID1 regulates the strength of IFN-I signaling and IFN-I-induced antiviral activity by promoting the degradation of IFNAR2. These findings provide a potential target for improving the antiviral efficacy of IFN-I.
Review
Microbiology
Jim Zoladek, Sebastien Nisole
Summary: Mosquito-borne flaviviruses pose a global public health concern, and understanding how they evade the host immune system could help in developing countermeasures.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Cell Biology
Yaoxing Wu, Shouheng Jin, Qingxiang Liu, Yu Zhang, Ling Ma, Zhiyao Zhao, Shuai Yang, Yi-Ping Li, Jun Cui
Summary: IRF3, a critical transcription factor in antiviral innate immune signaling, is regulated by CALCOCO2 and PSMD14. CALCOCO2 promotes autophagic degradation of IRF3, while PSMD14 prevents such degradation, maintaining IRF3 activity and fine-tuning immune response against viral infection.
Review
Neurosciences
Sophie A. I. Sanford, William A. McEwan
Summary: The presence of type-I interferons (IFNs) and their associated gene expression signatures in neurodegenerative diseases suggests their potential role in the progression of these diseases. The effects of type-I IFN response can be both protective and damaging, depending on the context and duration. Understanding the influence of type-I IFNs on diseases like Alzheimer's and tauopathies may lead to new therapeutic targets.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Fisheries
Yinghui Qin, Haixiang Liu, Peipei Zhang, Si Deng, Reng Qiu, Lunguang Yao
Summary: In this study, a STAT2 gene from orange-spotted grouper was cloned and characterized. The findings suggest that EcSTAT2 exerts antiviral activity against red-spotted grouper nervous necrosis virus through up-regulation of host interferon response.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Immunology
Gaofeng Zhu, Mihaly Badonyi, Lina Franklin, Luis Seabra, Gillian I. Rice, Anne-Boland-Auge, Jean-Francois Deleuze, Salima El-Chehadeh, Mathieu Anheim, Anne de Saint-Martin, Sandra A. Pellegrini, Joseph J. Marsh, Yanick Crow, Marie-Therese El-Daher
Summary: This study describes a rare homozygous missense STAT2 mutation (p.(A219V)) associated with enhanced IFN-I signaling, developmental delay, and up-regulation of ISG expression in blood. In vitro experiments showed that the p.(A219V) mutation not only transduced IFN-I stimulus, but also resulted in sustained STAT2 phosphorylation and ISG up-regulation, indicating impaired negative regulatory role of STAT2 p.(A219V) in IFN-I signaling. Therefore, mutations in STAT2 gene may lead to defective activation of the IFN-I signaling pathway and the occurrence of related diseases.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ioannis Kienes, Tanja Weidl, Nora Mirza, Mathias Chamaillard, Thomas A. Kufer
Summary: Type I interferon signaling is crucial for immune responses to viruses, fungi, or bacteria, but the amplitude and timing of the response are also key to preventing inadequate outcomes or tissue damage. NLRs, a family of proteins capable of sensing microbial products and signals related to tissue injury, regulate the quality of interferon signaling. Current understanding of the function of NLRs in type I interferon responses is incomplete, but they play important roles in influencing the immune response to viral infections and the development of autoimmunity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Bishara J. Freij, Aidan T. Hanrath, Rui Chen, Sophie Hambleton, Christopher J. A. Duncan
Summary: This study identified a novel genetic cause of homozygous STAT2 deficiency with unique clinical features, including HLH, severe influenza, and vaccine-strain varicella. Genetic investigation revealed a novel nonsense STAT2 variant that led to a lack of STAT2 protein expression and impaired IFN-I signaling. The occurrence of life-threatening influenza and vaccine-strain varicella in association with STAT2 deficiency highlights the critical role of IFN-I/III immunity in viral infections and vaccine responses.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Zhongshun Liu, Congwei Jiang, Zhangmengxue Lei, Sihan Dong, Linlin Kuang, Chenxu Huang, Ying Gao, Mu Liu, Hui Xiao, Patrick Legembre, Jae U. Jung, Huaping Liang, Xiaozhen Liang
Summary: Type I interferons (IFNs) are the first line of defense against invading pathogens. This study identified a previously unknown protein, PINLYP, that interacts with TBK1 to induce the production of type I IFN. Loss of PINLYP impaired the activation of IRF3 and the production of IFN induced by various viruses and Toll-like receptor ligands. Mice lacking PINLYP were more susceptible to lethal virus infection, highlighting the importance of PINLYP in the host defense against viral infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Ashley A. Stegelmeier, Maedeh Darzianiazizi, Kiersten Hanada, Shayan Sharif, Sarah K. Wootton, Byram W. Bridle, Khalil Karimi
Summary: Interferons play a crucial role in regulating host antiviral response, while neutrophils contribute to antiviral defense as host cells. The complex cross-regulatory talk between interferons and neutrophils is essential for initiating appropriate antiviral immune responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Zixuan Wang, Jing Xu, Jianhua Feng, Kaizheng Wu, Kangyong Chen, Zhao Jia, Xiaozhen Zhu, Wenji Huang, Xin Zhao, Qin Liu, Bangjie Wang, Xinhua Chen, Junya Wang, Jun Zou
Summary: This study reveals the interaction mechanism between fish type I interferons and receptors by solving the crystal structure of grass carp IFNa. The results show that fish type I interferons may interact with receptors in a different way compared to their mammalian homologs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Yu-Hui Li, Jiang-Ling Peng, Zhi-Sheng Xu, Mei-Guang Xiong, Huang-Ning Wu, Su-Yun Wang, Dan Li, Guo-Qiang Zhu, Yong Ran, Yan-Yi Wang
Summary: African swine fever virus (ASFV) is a large DNA virus that causes acute and hemorrhagic disease in pigs. In this study, researchers identified an ASFV cysteine protease pS273R as an antagonist of type I interferon (IFN). The pS273R protein inhibits the JAK-STAT signaling pathway triggered by type I IFNs, and its mechanism involves the degradation of STAT2 through ubiquitination.
JOURNAL OF VIROLOGY
(2023)
Article
Immunology
Adrian M. Shields, Ariharan Anantharachagan, Gururaj Arumugakani, Kenneth Baker, Sameer Bahal, Helen Baxendale, William Bermingham, Malini Bhole, Evon Boules, Philip Bright, Charu Chopra, Lucy Cliffe, Betsy Cleave, John Dempster, Lisa Devlin, Fatima Dhalla, Lavanya Diwakar, Elizabeth Drewe, Christopher Duncan, Magdalena Dziadzio, Suzanne Elcombe, Shuayb Elkhalifa, Andrew Gennery, Harichandrana Ghanta, Sarah Goddard, Sofia Grigoriadou, Scott Hackett, Grant Hayman, Richard Herriot, Archana Herwadkar, Aarnoud Huissoon, Rashmi Jain, Stephen Jolles, Sarah Johnston, Sujoy Khan, James Laffan, Peter Lane, Lucy Leeman, David M. Lowe, Shanti Mahabir, Dylan James Mac Lochlainn, Elizabeth McDermott, Siraj Misbah, Fiona Moghaddas, Hadeil Morsi, Sai Murng, Sadia Noorani, Rachael O'Brien, Smita Patel, Arthur Price, Tasneem Rahman, Suranjith Seneviratne, Anna Shrimpton, Catherine Stroud, Moira Thomas, Katie Townsend, Prashantha Vaitla, Nisha Verma, Anthony Williams, Siobhan O. Burns, Sinisa Savic, Alex G. Richter
Summary: This study investigates the outcomes of 310 patients with primary or secondary immunodeficiency in the United Kingdom following SARS-CoV-2 infection, and finds significantly elevated mortality rates in both cohorts compared to the general population. Increasing age, pre-existing lymphopenia, and other co-morbidities are identified as additional risk factors for death from COVID-19 in this cohort.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Medicine, General & Internal
Peter W. Horby, Guilherme Pessoa-Amorim, Natalie Staplin, Jonathan R. Emberson, Mark Campbell, Enti Spata, Leon Peto, Nigel J. Brunskill, Simon Tiberi, Victor Chew, Thomas Brown, Hasan Tahir, Beate Ebert, David Chadwick, Tony Whitehouse, Rahuldeb Sarkar, Clive Graham, J. Kenneth Baillie, Buddha Basnyat, Maya H. Buch, Lucy C. Chappell, Jeremy Day, Saul N. Faust, Raph L. Hamers, Thomas Jaki, Edmund Juszczak, Katie Jeffery, Wei Shen Lim, Alan Montgomery, Andrew Mumford, Kathryn Rowan, Guy Thwaites, Marion Mafham, Richard Haynes, Martin J. Landray
Summary: In patients hospitalized with COVID-19, aspirin was not associated with reductions in 28-day mortality or in the risk of progressing to invasive mechanical ventilation or death, but was associated with a small increase in the rate of being discharged alive within 28 days.
Article
Medicine, General & Internal
Arabella S. Stuart, Robert H. Shaw, Xinxue Liu, Melanie Greenland, Parvinder K. Aley, Nick J. Andrews, J. C. Cameron, Sue Charlton, Elizabeth A. Clutterbuck, Andrea M. Collins, Tom Darton, Tanya Dinesh, Christopher J. A. Duncan, Anna England, Saul N. Faust, Daniela M. Ferreira, Adam Finn, Anna L. Goodman, Christopher A. Green, Bassam Hallis, Paul T. Heath, Helen Hill, Bryn M. Horsington, Teresa Lambe, Rajeka Lazarus, Vincenzo Libri, Patrick J. Lillie, Yama F. Mujadidi, Ruth Payne, Emma L. Plested, Samuel Provstgaard-Morys, Maheshi N. Ramasamy, Mary Ramsay, Robert C. Read, Hannah Robinson, Gavin R. Screaton, Nisha Singh, David P. J. Turner, Paul J. Turner, Iason Vichos, Rachel White, Jonathan S. Nguyen-Van-Tam, Matthew D. Snape
Summary: The study investigated the mixed use of different COVID-19 vaccines within the same schedule, showing that in certain conditions, heterologous vaccination can achieve similar immunogenicity to homologous vaccination, facilitating rapid global vaccine deployment.
Article
Urology & Nephrology
Rachel K. Y. Hung, Elizabeth Binns-Roemer, John W. Booth, Rachel Hilton, Mark Harber, Beatriz Santana-Suarez, Lucy Campbell, Julie Fox, Andrew Ustianowski, Catherine Cosgrove, James E. Burns, Amanda Clarke, David A. Price, David Chadwick, Denis Onyango, Lisa Hamzah, Kate Bramham, Caroline A. Sabin, Cheryl A. Winkler, Frank A. Post
Summary: APOL1 high-risk genotypes are strongly associated with kidney disease in people of African ancestry with HIV and account for approximately half of ESKD cases in this cohort.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Urology & Nephrology
Rachel K. Y. Hung, Elizabeth Binns-Roemer, John W. Booth, Rachel Hilton, Julie Fox, Fiona Burns, Mark Harber, Andrew Ustianowski, Lisa Hamzah, James E. Burns, Amanda Clarke, David A. Price, Stephen Kegg, Denis Onyango, Beatriz Santana-Suarez, Lucy Campbell, Kate Bramham, Claire C. Sharpe, Caroline A. Sabin, Cheryl A. Winkler, Frank A. Post
Summary: This study investigated the association between sickle cell trait (SCT) and kidney disease in people of African ancestry with HIV in the UK. The results showed that individuals with SCT were more likely to have lower glomerular filtration rate, proteinuria, and albuminuria. These associations were particularly significant in participants with low-risk APOL1 genotypes.
KIDNEY INTERNATIONAL REPORTS
(2022)
Article
Infectious Diseases
Adrienn Angyal, Stephanie Longet, Shona C. Moore, Rebecca P. Payne, Adam Harding, Tom Tipton, Patpong Rongkard, Mohammad Ali, Luisa M. Hering, Naomi Meardon, James Austin, Rebecca Brown, Donal Skelly, Natalie Gillson, Sue L. Dobson, Andrew Cross, Gurjinder Sandhar, Jonathan A. Kilby, Jessica K. Tyerman, Alexander R. Nicols, Jarmila S. Spegarova, Hema Mehta, Hailey Hornsby, Rachel Whitham, Christopher P. Conlon, Katie Jeffery, Philip Goulder, John Frater, Christina Dold, Matthew Pace, Ane Ogbe, Helen Brown, M. Azim Ansari, Emily Adland, Anthony Brown, Meera Chand, Adrian Shields, Philippa C. Matthews, Susan Hopkins, Victoria Hall, William James, Sarah L. Rowland-Jones, Paul Klenerman, Susanna Dunachie, Alex Richter, Christopher J. A. Duncan, Eleanor Barnes, Miles Carroll, Lance Turtle, Thushan de Silva
Summary: This study compares immune responses to the BNT162b2 mRNA vaccine in healthcare workers with and without previous SARS-CoV-2 infection. The results show that previously infected individuals have stronger spike-specific T-cell and antibody responses after receiving a single dose of the vaccine compared to SARS-CoV-2-naive individuals. This suggests that a single dose of the BNT162b2 vaccine is likely to provide better protection against SARS-CoV-2 infection in individuals with previous infection.
Article
Gastroenterology & Hepatology
Paulina Dirvanskyte, Bhaskar Gurram, Chrissy Bolton, Neil Warner, Kelsey D. J. Jones, Helen R. Griffin, Jason Y. Park, Klaus-Michael Keller, Kimberly C. Gilmour, Sophie Hambleton, Aleixo M. Muise, Christian Wysocki, Holm H. Uhlig
Summary: Turner syndrome is associated with increased susceptibility to intestinal inflammation, while other chromosomal abnormalities' contribution to IBD susceptibility is unclear. Some gene deletions are associated with IBD, but they are also detected in healthy populations, suggesting overestimation of IBD expressivity. The duplication of IL2RA/IL15R loci may contribute to IBD risk.
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Cell & Tissue Engineering
Robert M. Jackson, Catherine F. Hatton, Jarmila Stremenova Spegarova, Maria Georgiou, Joseph Collin, Emily Stephenson, Bernard Verdon, Iram J. Haq, Rafiqul Hussain, Jonathan M. Coxhead, Hardeep-Singh Mudhar, Bart Wagner, Megan Hasoon, Tracey Davey, Paul Rooney, C. M. Anjam Khan, Chris Ward, Malcolm Brodlie, Muzlifah Haniffa, Sophie Hambleton, Lyle Armstrong, Francisco Figueiredo, Rachel Queen, Christopher J. A. Duncan, Majlinda Lako
Summary: Conjunctival epithelial cells, the largest exposed epithelium of the ocular surface tissue, may serve as a potential route for SARS-CoV-2 entry. Through the use of an organotypic model and molecular assays, it was found that although conjunctival cells are susceptible to SARS-CoV-2 infection, productive infection does not occur. Furthermore, the early innate immune response in conjunctival cells is characterized by robust NF-KB activity without activation of antiviral interferon signaling.
Article
Microbiology
Brian J. Willett, Joe Grove, Oscar A. MacLean, Craig Wilkie, Giuditta De Lorenzo, Wilhelm Furnon, Diego Cantoni, Sam Scott, Nicola Logan, Shirin Ashraf, Maria Manali, Agnieszka Szemiel, Vanessa Cowton, Elen Vink, William T. Harvey, Chris Davis, Patawee Asamaphan, Katherine Smollett, Lily Tong, Richard Orton, Joseph Hughes, Poppy Holland, Vanessa Silva, David J. Pascall, Kathryn Puxty, Ana da Silva Filipe, Gonzalo Yebra, Sharif Shaaban, Matthew T. G. Holden, Rute Maria Pinto, Rory Gunson, Kate Templeton, Pablo R. Murcia, Arvind H. Patel, Paul Klenerman, Susanna Dunachie, John Haughney, David L. Robertson, Massimo Palmarini, Surajit Ray, Emma C. Thomson
Summary: Vaccines based on the spike protein of SARS-CoV-2 are vital in combating COVID-19, but the emergence of the Omicron variant poses a threat to this strategy. Studies have shown that the Omicron variant evades neutralization by sera from individuals vaccinated with different vaccines and reduces real-world vaccine effectiveness, although booster vaccination can partially restore its effectiveness. Additionally, the Omicron variant exhibits distinct cell entry pathways and phenotypes, which may contribute to its rapid global spread and altered pathogenicity.
NATURE MICROBIOLOGY
(2022)
Letter
Hematology
Adam Al-Hakim, James A. Poulter, Dina Mahmoud, Ailsa M. S. Rose, Suzanne Elcombe, Helen Lachmann, Catherine Cargo, Christopher J. A. Duncan, Mark Bishton, Venetia Bigley, Anjum Khan, Sinisa Savic
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Infectious Diseases
Rajeka Lazarus, Christian Taucher, Claire Brown, Irena Corbic Ramljak, Leon Danon, Katrin Dubischar, Christopher J. A. Duncan, Susanne Eder-Lingelbach, Saul N. Faust, Christopher Green, Karishma Gokani, Romana Hochreiter, Johanna Kellett Wright, Dowan Kwon, Alexander Middleditch, Alasdair P. S. Munro, Kush Naker, Florentina Penciu, David Price, Benedicte Querton, Tawassal Riaz, Amy Ross-Russell, Amada Sanchez-Gonzalez, Hayley Wardle, Sarah Warren, Adam Finn
Summary: This study evaluated the safety and optimal dose of a novel inactivated whole-virus adju-vanted vaccine against SARS-CoV-2. The results showed that the vaccine was well tolerated in all tested dose groups, and no safety concerns were identified. The highest dose group exhibited significantly stronger immunogenicity and was chosen for phase 3 clinical development.
JOURNAL OF INFECTION
(2022)
Article
Infectious Diseases
Karin Hardt, An Vandebosch, Jerald Sadoff, Mathieu Le Gars, Carla Truyers, David Lowson, Ilse Van Dromme, Johan Vingerhoets, Tobias Kamphuis, Gert Scheper, Javier Ruiz-Guinazu, Saul N. Faust, Christoph D. Spinner, Hanneke Schuitemaker, Johan Van Hoof, Macaya Douoguih, Frank Struyf
Summary: This study investigated the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose. The results showed that a homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19.
LANCET INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Alexander J. Mentzer, Daniel O'Connor, Sagida Bibi, Irina L. Chelysheva, Elizabeth A. Clutterbuck, Tesfaye Demissie, Tanya Dinesh, Nick M. Edwards, Sally Felle, Shuo C. Feng, Amy Flaxman, Eleanor Karp-Tatham, Grace Li, Xinxue J. Liu, Natalie Marchevsky, Leila Godfrey, Rebecca K. Makinson, Maireid O. Bull, Jamie N. Fowler, Bana Alamad, Tomas Malinauskas, Amanda Chong, Katherine Sanders, Robert Shaw, Merryn Voysey, Matthew D. Snape, Andrew J. Pollard, Teresa Lambe, Julian C. Knight
Summary: Variation in antibody levels elicited by the COVID-19 vaccine ChAdOx1 nCov-19 is linked to specific major histocompatibility complex class II alleles, providing insight into the breadth of immune response among vaccinated individuals. HLA-DQB1*06 allele is associated with higher levels of anti-RBD antibody and decreased risk of breakthrough infection. These findings have implications for future vaccine design and implementation.
Article
Immunology
Stephanie Longet, Alexander Hargreaves, Saoirse Healy, Rebecca Brown, Hailey R. Hornsby, Naomi Meardon, Tom Tipton, Eleanor Barnes, Susanna Dunachie, Christopher J. A. Duncan, Paul Klenerman, Alex Richter, Lance Turtle, Thushan I. de Silva, Miles W. Carroll
Summary: Two doses of BNT162b2 mRNA vaccine induce a strong systemic humoral response to SARS-CoV-2, but mucosal immune response is important for defense against airborne transmission. This study characterizes the IgG responses to SARS-CoV-2 and other coronaviruses in oral fluid and plasma samples from UK healthcare workers. It also investigates the impact of previous infection and additional vaccine doses on the immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)