Article
Microbiology
Emily R. Albright, Clayton K. Mickelson, Robert F. Kalejta
Summary: This study identified that the HCMV latency protein UL138 inhibits the cGAS/STING/TBK1 innate immunity pathway, not only during infection but also during viral latency. This finding helps to understand how innate immunity or its neutralization impacts long-term persistence by HCMV and other latent viruses.
Review
Immunology
Ximing Jin, Wenjia Wang, Xinwei Zhao, Wenhua Jiang, Qingqing Shao, Zhuo Chen, Cong Huang
Summary: The incidence of human herpesvirus (HHVs) is increasing and has impacted a wide range of population. The cGAS-STING pathway plays a crucial role in human diseases, particularly in HHV infections, and viruses have evolved strategies to evade this pathway to escape immune detection. The modulation of the cGAS-STING pathway has become a potential therapeutic target for the development of antiviral drugs and vaccines, as well as the investigation of disease models related to this pathway.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Virology
Huifang Zhu, Rongzhao Zhang, Li Yi, Yan-Dong Tang, Chunfu Zheng
Summary: This study demonstrates that UNC93B1 acts as a crucial regulator of STING, attenuating its signaling pathway through autophagy-lysosome degradation, and provides novel insights into UNC93B1's function in antiviral innate immunity.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Review
Cell Biology
Yang Yu, Jingyang Liu, Cun Liu, Ruijuan Liu, Lijuan Liu, Zhenhai Yu, Jing Zhuang, Changgang Sun
Summary: Innate immune mechanisms initiate immune responses through pattern-recognition receptors (PRRs). Cyclic GMP-AMP synthase (cGAS), a member of PRRs, senses various pathogenic or endogenous DNA and activates innate immune signaling pathways, regulating the development of adaptive immune response. Post-translational modifications (PTMs) of the cGAS-STING pathway play a crucial role in its functional regulation.
Article
Biochemistry & Molecular Biology
Yutong Li, Juntao Bie, Chen Song, Yunfei Li, Tianzhuo Zhang, Haishuang Li, Long Zhao, Fuping You, Jianyuan Luo
Summary: This study reveals that SIRT2 negatively regulates the activation of cGAS through deacetylating G3BP1, indicating a potential antiviral strategy by modulating SIRT2 activity.
Article
Biochemistry & Molecular Biology
Wenwen Zheng, Zhenbang Zhou, Yajuan Rui, Runxin Ye, Fengyan Xia, Fei Guo, Xiaoman Liu, Jiaming Su, Meng Lou, Xiao-Fang Yu
Summary: It was discovered in this study that EV-A71 infection triggers STING activation through cGAS sensing. EV-A71 infection leads to mitochondrial damage and release of mitochondrial DNA into the cytosol. The viral protease 2A(pro) of EV-A71 was found to inhibit cGAS-STING activation. Restoring TRAF3 expression rescued the inhibition of cGAS-STING activation by 2A(pro).
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Review
Cell Biology
Yuting Yang, Yiming Huang, Zhenguo Zeng
Summary: Pathogens can produce conserved pathogen-associated molecular patterns (PAMPs) that are recognized by host pattern recognition receptors (PRRs). Recent studies have shown that cytoplasmic DNA receptors can specifically recognize exogenous DNA and activate interferon 1 (IFN1), which is a significant advancement in various research fields. The cGAS-STING signaling pathway is a critical natural immune pathway in cells and plays a crucial role in pathogen infection, tumors, and various autoimmune diseases in humans.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Immunology
Nanxin Liu, Xiaoxiao Pang, Hua Zhang, Ping Ji
Summary: The cGAS-STING pathway is crucial in protecting the host against viral infections and has also been found to play a role in response to bacterial infections. However, its functions in bacterial infections are more complex and diverse compared to viral infections, as the effects on the host vary depending on the bacterial species and infection mode.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Yang Du, Zhiqiang Hu, Yien Luo, Helen Y. Wang, Xiao Yu, Rong-Fu Wang
Summary: The DNA-sensing receptor cGAS and its downstream signaling adaptor STING play crucial roles in immune defense against infectious pathogens, and the interplay between the cGAS-STING pathway and pathogens provides insight into the development of pharmacological approaches for treating infectious diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Oncology
Rui Wang, Aashiq Hussain, Quanquan Guo, Meimei Ma
Summary: DNA is highly immunogenic and can activate the cGAS-STING pathway, which plays a crucial role in the pathogenesis and progression of neoplastic diseases. The modulation of cGAS-STING signaling holds great promise for cancer therapy, although there are disagreements on whether to activate or inhibit this pathway.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2024)
Article
Immunology
Weijie Ouyang, Shoubi Wang, Jiaoyue Hu, Zuguo Liu
Summary: Dry eye is a common ocular surface disease that significantly affects the quality of life. The mechanism of dry eye, an immune-related disease, is not fully understood. The newly discovered cGAS-STING pathway plays an important role in autoimmune and inflammatory diseases by recognizing dsDNA. The release of dsDNA is associated with dry eye.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Wanglong Zheng, Anjing Liu, Nengwen Xia, Nanhua Chen, Francois Meurens, Jianzhong Zhu
Summary: The cGAS-STING signaling axis is activated by cytosolic DNA, both non-self and self DNA. This pathway is used by the innate immune system to monitor invading pathogens and/or damage. It not only facilitates inflammatory responses and IFN production, but also activates other cellular processes like apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Wanglong Zheng, Nengwen Xia, Jiajia Zhang, Nanhua Chen, Francois Meurens, Zongping Liu, Jianzhong Zhu
Summary: The cGAS-STING pathway is involved in triggering both canonical and non-canonical autophagy, which plays crucial roles in balancing innate immune responses, maintaining intracellular environmental homeostasis, alleviating liver injury, and limiting tumor growth and transformation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Yongai Xiong, Yan-Dong Tang, Chunfu Zheng
Summary: The manuscript discusses the role of cytosolic nucleic acid sensors during microbial infections and cell death, as well as the interaction between the caspase family and the cGAS-STING signaling pathway. This sheds light on novel therapeutic approaches targeting antiviral innate immunity, cancer, inflammatory diseases, and autoimmunity.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Review
Immunology
Zhe Ge, Shuzhe Ding
Summary: This paper summarizes the regulatory mechanism of the cGAS/STING signaling pathway and the immune escape mechanism of corresponding viruses, aiming to provide targeted immunotherapy ideas for specific viral infections in the future.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Dermatology
Cinzia Borgogna, Licia Martuscelli, Carlotta Olivero, Irene Lo Cigno, Marco De Andrea, Valeria Caneparo, Renzo Boldorini, Girish Patel, Marisa Gariglio
Summary: The combination of HPV infection, immune defects, and UVB exposure promotes skin cancer development.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Silvia Albertini, Licia Martuscelli, Cinzia Borgogna, Sanamjeet Virdi, Daniela Indenbirken, Irene Lo Cigno, Gloria Griffante, Federica Calati, Renzo Boldorini, Nicole Fischer, Marisa Gariglio
Summary: The tumor microenvironment, consisting of extracellular matrix, blood vessels, immune cells, and fibroblasts, plays a crucial role in cancer development. However, its involvement in Merkel cell carcinoma (MCC) is unknown. In this study, we characterized cancer-associated fibroblasts (CAFs) in patient-derived xenografts of MCC. We found that injection of patient-derived CAFs with MCC cells promoted tumor growth and metastasis, mainly localized around blood vessels. We identified aminopeptidase A as a potential marker for MCC prognosis and therapeutic target.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Virology
Alice Monzani, Cinzia Borgogna, Daniela Ferrante, Benedetta Ciacchini, Enrico Felici, Marisa Gariglio, Ivana Rabbone
Summary: The choice of the best SARS-CoV-2 detection approach is crucial to predict the high-risk spreaders among children. This study found that children with nasopharyngeal symptoms have higher levels of viral load in saliva, indicating a greater likelihood of spreading the virus. In contrast, asymptomatic children have low viral load and are unlikely to transmit the virus.
Article
Dermatology
Angelo Valerio V. Marzano, Chiara Moltrasio, Giovanni Genovese, Marco De Andrea, Valeria Caneparo, Pamela Vezzoli, Denise Morotti, Paolo Sena, Marina Venturini, Simonetta Battocchio, Valentina Caputo, Nathalie Rizzo, Carlo Alberto Maronese, Luigia Venegoni, Francesca Laura Boggio, Franco Rongioletti, Piergiacomo Calzavara-Pinton, Emilio Berti
Summary: This study aimed to investigate the relationship between COVID-19 and skin manifestations, and found that SARS-CoV-2 was detected in only 38% of patients' skin samples. The research suggests that the occurrence of skin lesions mainly depends on the activation of the immune system, rather than a specific cutaneous phenotype.
Article
Oncology
Judit Kisistok, Ditte Sigaard Christensen, Mads Heilskov Rasmussen, Lone Duval, Ninna Aggerholm-Pedersen, Adam Andrzej Luczak, Boe Sandahl Sorensen, Martin Roelsgaard Jakobsen, Trine Heide Oellegaard, Nicolai Juul Birkbak
Summary: Immunotherapy has dramatically improved the treatment outcomes for metastatic melanoma patients, but it also brings immune-related adverse events. Identifying nonresponding patients early is crucial, and this study explores the use of circulating tumor DNA (ctDNA) analysis as a minimally invasive tool. In a cohort of 24 melanoma patients, the presence of ctDNA was associated with poor prognosis, suggesting its potential to be used in clinical practice.
Article
Oncology
Carlo Girone, Federica Calati, Irene Lo Cigno, Valentina Salvi, Valentina Tassinari, Tiziana Schioppa, Cinzia Borgogna, Ludovica Lospinoso Severini, John Hiscott, Cristina Cerboni, Alessandra Soriani, Daniela Bosisio, Marisa Gariglio
Summary: Activation of RIG-I pathway can effectively treat HPV-associated malignancies by inducing cell apoptosis and enhancing immune cell activity. This strategy has shown promising results in in vitro experiments and mouse models, and holds important implications for clinical treatment and research.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Virology
Alessia Spadavecchia, Francesco Cresi, Agata Leone, Valentina Dell'Oste, Matteo Biolatti, Ganna Galitska, Alessandra Coscia, Sonia Deantoni, Cinzia Valenza, Enrico Bertino, Chiara Peila
Summary: This short communication explores the correlation between virological features of different HCMV strains and clinical phenotypes of congenitally infected newborns, proposing new possible prognostic factors.
JOURNAL OF CLINICAL VIROLOGY
(2023)
Article
Virology
Elisa Fanunza, Adam Z. Z. Cheng, Ashley A. Auerbach, Bojana Stefanovska, Sofia N. Moraes, James R. Lokensgard, Matteo Biolatti, Valentina Dell'Oste, Craig J. Bierle, Wade A. Bresnahan, Reuben S. Harris
Summary: Human cytomegalovirus (HCMV) infections can range from asymptomatic to severe. HCMV has developed strategies to overcome host-encoded antiviral defenses. HCMV infection causes APOBEC3B to relocalize from the nuclear compartment to the cytoplasm, suggesting a potential antiviral strategy against HCMV.
JOURNAL OF VIROLOGY
(2023)
Article
Chemistry, Medicinal
Matteo Biolatti, Marco Blangetti, Melissa Baggieri, Antonella Marchi, Silvia Gioacchini, Greta Bajetto, Davide Arnodo, Paola Bucci, Raoul Fioravanti, Maedeh Kojouri, Matteo Bersani, Giulia D'Arrigo, Lydia Siragusa, Simone Ghinato, Marco De Andrea, Francesca Gugliesi, Camilla Albano, Selina Pasquero, Ivan Visentin, Emilio D'Ugo, Francesca Esposito, Paolo Malune, Enzo Tramontano, Cristina Prandi, Francesca Spyrakis, Fabio Magurano, Valentina Dell'Oste
Summary: The SARS-CoV-2 pandemic and the possibility of emerging coronavirus strains highlight the urgent need for new pan-coronavirus inhibitors. Strigolactones (SLs), a class of plant hormones, have been found to have antiviral activity against herpesviruses including human cytomegalovirus (HCMV). This study shows that synthetic SLs can inhibit the replication of β-coronaviruses such as SARS-CoV-2 and HCoV-OC43. In silico simulations suggest that SLs bind to the active site of the SARS-CoV-2 main protease, which was confirmed by in vitro assays. These findings indicate the potential efficacy of SLs as broad-spectrum antivirals against β-coronaviruses and suggest their possible repurposing for COVID-19 treatment.
ACS INFECTIOUS DISEASES
(2023)
Article
Cell Biology
Aida S. S. Hansen, Lea S. S. Jensen, Kristine R. R. Gammelgaard, Kristoffer G. G. Ryttersgaard, Christian Krapp, Jesper Just, Kasper L. L. Jonsson, Pia B. B. Jensen, Thomas Boesen, Mogens Johansen, Anders Etzerodt, Bent W. W. Deleuran, Martin R. R. Jakobsen
Summary: This article introduces the highly immunosuppressive tumor microenvironment, and explores a novel method to improve immunotherapy effectiveness by activating the STING signaling pathway. The researchers found that extracellular vesicles derived from activated CD4(+) T cells can sensitize macrophages and activate the STING pathway, effectively disrupting the immune suppressive environment in the tumor and priming for a robust immune response towards STING activation.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Multidisciplinary Sciences
Lamin B. Cham, Jesper D. Gunst, Mariane H. Schleimann, Giacomo S. Frattari, Miriam Rosas-Umbert, Line K. Vibholm, Renee M. van der Sluis, Martin R. Jakobsen, Rikke Olesen, Lin Lin, Martin Tolstrup, Ole S. Sogaard
Summary: In this study, single-cell RNA sequencing was used to obtain four distinct pDC clusters, including a cytotoxic-like pDC cluster, which expressed both antiviral and cytotoxic genes. The cytotoxic-like pDCs showed similar communication signals to other pDCs, and were found to be distinct from NK and T cells.