Article
Immunology
Elisa Fanunza, Fabrizio Carletti, Marina Quartu, Nicole Grandi, Laura Ermellino, Jessica Milia, Angela Corona, Maria Rosaria Capobianchi, Giuseppe Ippolito, Enzo Tramontano
Summary: The viral protein NS2A suppresses the IFN signaling and promotes degradation of STAT1 and STAT2 to evade the innate immune system, helping Zika Virus escape host immune responses. Antagonism against IFN plays a crucial role in flavivirus virulence, and understanding how Zika Virus evades IFN response can pave the way for new strategies to attenuate the pathogenesis.
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
Jun Shu, Xiao Ma, Yang Zhang, Jingyi Zou, Zhenghong Yuan, Zhigang Yi
Summary: Flaviviruses, including Zika virus, have the ability to antagonize host interferon signaling, leading to suppression of host de novo protein synthesis and degradation of specific proteins. Understanding these mechanisms may provide insights for developing novel antiviral approaches.
EMERGING MICROBES & INFECTIONS
(2021)
Article
Cell Biology
Binbin Xue, Huiyi Li, Shun Liu, Qing Feng, Yan Xu, Rilin Deng, Shengwen Chen, Jingjing Wang, Xinran Li, Mengyu Wan, Songqing Tang, Haizhen Zhu
Summary: This study reveals the crucial role of methionine oxidation in immune function, particularly in the activation of STAT2. The interference of methionine oxidation on STAT2 activation can be prevented by IFN treatment through the recruitment of methionine sulfoxide reductase MSRB2, which is enhanced by NAT9. The findings may provide insights into the clinical applications of IFN in immune-related diseases.
Article
Oncology
Juyeong Hong, Ji Hoon Lee, Zhao Zhang, Yanming Wu, Mei Yang, Yiji Liao, Richard de la Rosa, Jessica Scheirer, Douglas Pechacek, Nu Zhang, Zhenming Xu, Tyler Curiel, Xi Tan, Tim H. -M. Huang, Kexin Xu
Summary: Inhibition of cancer-intrinsic EZH2 promotes antitumor immunity in breast cancer, requiring specific activation of type I IFN signaling. High levels of EZH2 and low levels of STAT2 in breast cancer patients are associated with the worst antitumor immune responses.
Article
Virology
Nico Becker, Andrea Maisner
Summary: Nipah virus (NiV) inhibits the antiviral response of infected cells by sequestering STAT1 and STAT2 into cytosolic inclusion bodies (IBs), thereby blocking IFN signaling. This mechanism, involving the virus phosphoprotein (P), limits the phosphorylation/activation and nuclear translocation of STAT proteins, leading to a lack of nuclear pSTAT in NiV-infected cells. This study provides the first evidence that cytosolic NiV IBs play a functional role in IFN antagonism.
Article
Microbiology
Callum Talbot-Cooper, Teodors Pantelejevs, John P. Shannon, Christian R. Cherry, Marcus T. Au, Marko Hyvonen, Heather D. Hickman, Geoffrey L. Smith
Summary: This study reports that the poxvirus protein 018 inhibits interferon-induced signaling by binding to the SH2 domain of STAT1. The crystal structure of the 018:STAT1 complex reveals a phosphotyrosine-independent mode of 018 binding to STAT1, and the STAT1-binding motif of 018 shows similarity to STAT1-binding proteins from Nipah virus.
CELL HOST & MICROBE
(2022)
Article
Virology
Pathum Ekanayaka, Byeong-Hoon Lee, Asela Weerawardhana, Kiramage Chathuranga, Jong-Hyeon Park, Jong-Soo Lee
Summary: Research has shown that the Foot-and-mouth disease virus protein VP3 interacts specifically with the transmembrane domain of MAVS, inhibiting the localization of MAVS to mitochondria and suppressing the type-I IFN response, thus promoting viral replication.
Article
Virology
Qingsen Wang, Wenliang Pan, Song Wang, Chen Pan, Hongya Ning, Shile Huang, Shih-Hsin Chiu, Ji-Long Chen
Summary: The study demonstrates that influenza A virus (IAV) suppresses antiviral innate immunity by activating EGFR/ERK signaling and induces activation of protein tyrosine phosphatase SHP2, which modulates EGFR-mediated ERK activity and antiviral effectiveness. SHP2 acts as a key signal transducer between EGFR and ERK during IAV infection, playing a crucial role in suppressing host innate immunity.
JOURNAL OF VIROLOGY
(2021)
Article
Medicine, Research & Experimental
Eun-Bin Kwon, Young Soo Kim, Sang Mi Han, Se-Gun Kim, Jang-Gi Choi
Summary: This study found that Tilia amurensis honey (TH) can suppress influenza A virus infection by regulating the immune response in macrophages. TH increases the production of type-1 interferon and proinflammatory cytokines, and enhances the phosphorylation of related proteins, which interfere with virus replication and entry.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
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
Pharmacology & Pharmacy
Wei -Chun Chen, Chung-Hao Huang, Wangta Liu, Jin-Ching Lee
Summary: Dengue virus (DENV) infection is a life-threatening disease with no effective treatment options. However, a study found that sulforaphane (SFN) has significant antiviral activity against DENV by inducing heme oxygenase-1 (HO-1) expression and inhibiting viral protease activity. This suggests that SFN could be a promising candidate for treating DENV.
ANTIVIRAL RESEARCH
(2022)
Article
Immunology
Farjana Ahmed, Matloob Husain
Summary: NAA60, a recently discovered N-terminal acetyltransferase, plays a proviral role during influenza A virus infection by interfering with the interferon alpha signaling pathway.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Daniel Schnepf, Stefania Crotta, Thiprampai Thamamongood, Megan Stanifer, Laura Polcik, Annette Ohnemus, Juliane Vier, Celia Jakob, Miriam Llorian, Hans Henrik Gad, Rune Hartmann, Birgit Strobl, Susanne Kirschnek, Steeve Boulant, Martin Schwemmle, Andreas Wack, Peter Staeheli
Summary: Selective TYK2 inhibitors preferentially block potentially detrimental type I interferon signaling while preserving IFN-lambda responses, suggesting a superior treatment option for type I interferonopathies. In contrast, JAK1/2 inhibitors equally block IFN-alpha/beta or IFN-gamma-driven responses.
SCIENCE IMMUNOLOGY
(2021)
Article
Virology
Yishu Wang, Yiling Chen, Ying Lin, Yingqin Quan, Xiaoping Xiao, Renli Zhang
Summary: RSV infection is a major cause of lower respiratory tract disease, with no effective treatments found yet. Recent studies have shown that TRIM family member TRIM22 plays a crucial role in resisting RSV infection. RSV infection induces TRIM22 expression through the activation of JAK-STAT1/2 signaling.
JOURNAL OF MEDICAL VIROLOGY
(2021)
Editorial Material
Microbiology
Curt M. Horvath
CELL HOST & MICROBE
(2015)
Review
Biochemistry & Molecular Biology
Annie M. Bruns, Curt M. Horvath
Article
Biochemistry & Molecular Biology
Akihiko Komuro, Yuya Homma, Takaharu Negoro, Glen N. Barber, Curt M. Horvath
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2016)
Article
Microbiology
Darja Pollpeter, Maddy Parsons, Andrew E. Sobala, Sashika Coxhead, Rupert D. Lang, Annie M. Bruns, Stelios Papaioannou, James M. McDonnell, Luis Apolonia, Jamil A. Chowdhury, Curt M. Horvath, Michael H. Malim
NATURE MICROBIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Jean-Patrick Parisien, Jessica J. Lenoir, Roli Mandhana, Kenny R. Rodriguez, Kenin Qian, Annie M. Bruns, Curt M. Horvath
Article
Biochemistry & Molecular Biology
Roli Mandhana, Lily K. Qian, Curt M. Horvath
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
(2018)
Review
Biochemistry & Molecular Biology
Nancy Au-Yeung, Curt M. Horvath
CYTOKINE & GROWTH FACTOR REVIEWS
(2018)
Article
Biochemistry & Molecular Biology
Diana Saleiro, Gavin T. Blyth, Ewa M. Kosciuczuk, Patrick A. Ozark, Beata Majchrzak-Kita, Ahmet D. Arslan, Mariafausta Fischietti, Neha K. Reddy, Curt M. Horvath, Roger J. Davis, Eleanor N. Fish, Leonidas C. Platanias
Article
Multidisciplinary Sciences
Roli Mandhana, Curt M. Horvath
SCIENTIFIC REPORTS
(2018)
Article
Biochemistry & Molecular Biology
Kendra M. Quicke, Kristin Y. Kim, Curt M. Horvath, Mehul S. Suthar
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
(2019)
Article
Multidisciplinary Sciences
Rogan A. Grant, Luisa Morales-Nebreda, Nikolay S. Markov, Suchitra Swaminathan, Melissa Querrey, Estefany R. Guzman, Darryl A. Abbott, Helen K. Donnelly, Alvaro Donayre, Isaac A. Goldberg, Zasu M. Klug, Nicole Borkowski, Ziyan Lu, Hermon Kihshen, Yuliya Politanska, Lango Sichizya, Mengjia Kang, Ali Shilatifard, Chao Qi, Jon W. Lomasney, A. Christine Argento, Jacqueline M. Kruser, Elizabeth S. Malsin, Chiagozie O. Pickens, Sean B. Smith, James M. Walter, Anna E. Pawlowski, Daniel Schneider, Prasanth Nannapaneni, Hiam Abdala-Valencia, Ankit Bharat, Cara J. Gottardi, G. R. Scott Budinger, Alexander Misharin, Benjamin D. Singer, Richard G. Wunderink
Summary: The study found that patients infected with SARS-CoV-2 have enriched T cells and monocytes in the alveolar space, suggesting that the virus infects alveolar macrophages and induces T cell production of interferon-, leading to inflammation and persistent alveolitis.
Article
Cell Biology
Jessica J. Lenoir, Jean-Patrick Parisien, Curt M. Horvath
Summary: The study reveals that LGP2 inhibits K63-Ub chains by associating with and sequestering the K63-Ub-conjugating enzyme Ubc13/UBE2N, thereby affecting the regulation of a range of K63-Ub ligase proteins and immune signaling pathways.
Article
Virology
Curt M. Horvath, Rebecca E. Dutch, Charles J. Russell
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Jean-Patrick Parisien, Jessica J. Lenoir, Gloria Alvarado, Curt M. Horvath
Summary: The ability of Zika virus to degrade STAT2 protein in order to evade the host immune response is investigated in this study. The interaction between NS5 and STAT2 is found to be essential for proteasome-mediated degradation of STAT2. This research provides new insights into the mechanisms of Zika virus evasion and identifies potential targets for antiviral therapies.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Nancy Au-Yeung, Curt M. Horvath