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Journal of Molecular Cell Biology 2022年第4期14卷 18-26页

作者： Jun Li Samuel F.Bakhoum Human Oncology and Pathogenesis Program Memoria loan Kettering Cancer CenterNew YorkNY 10065USA Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA

Cytosolic dna is prevalent in cells constituting the tumor microenvironment(TME)and can activate the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)innate immune *** initiation,transmission,and execution of the cGAS-STING pathway can take place among different cell types within the TME and thus cGAS-STING may play opposing roles in driving tumor progression in addition to its tumor cell-intrinsic ***,we review recent advances in the cGAS-STING field with a focus on its crosstalk with other signaling pathways in the *** efforts to depict a more detailed picture of the roles of cGAS-STING signaling in the TME wil help design a better cancer treatment regime by targeting the cGAS-STING pathway more precisely.

关键词： immunity the tumor microenvironment dna sensing

The multifaceted functions of cGAS

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Journal of Molecular Cell Biology 2022年第5期14卷 16-26页

作者： Haipeng Liu Fei Wang Yajuan Cao Yifang Dang Baoxue Ge Clinical and Translational Research Center Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai 200433China Shanghai Key Laboratory of Tuberculosis Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai 200433China Central Laboratory Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghai 200433China

Pattern recognition receptors arecritical forthe sensing of pathogen-associated molecular patterns or danger-associated molecular patterns and subsequent mounting of innate immunityandshaping ofadaptive *** identification of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate(cGAMP)synthase(cGAS)as a major cytosolic dna receptor is a milestone in the field of dna *** engagement of cGAS by double-stranded dna from different origins,including invading pathogens,damaged mitochondria,ruptured micronuclei,and genomic dna results in the generation of cGAMP and activation of stimulator of interferon genes,which thereby activates innate immunity mainly characterized by the activation of type I interferon *** recent years,great progress has been made in understanding the subcellular localization and novel functions of *** this review,we particularlyfocus on summarizingthe multifaceted roles ofcGAS in regulating senescence,autophagy,cell stemness,apoptosis,angiogenesis,cell proliferation,antitumor effect,dna replication,dna damage repair,micronucleophagy,as well as cell metabolism.

关键词： cyclic GMP-AMP synthase(cGAS) stimulator of interferon genes(STING) dna sensing innate immunity micronucleophagy

The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies

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Virologica Sinica 2024年第5期39卷 709-718页

作者： Dong Fang Yan Liu Dou Dou Bin Su Department of Health Sciences National Natural Science Foundation of ChinaBeijing100085China Beijing Key Laboratory for HIV/AIDS Research Beijing Youan HospitalCapital Medical UniversityBeijing100069China Central Laboratory Beijing Youan HospitalCapital Medical UniversityBeijing100069China

Mpox is an infectious and contagious zoonotic disease caused by the mpox virus(MPXV),which belongs to the genus *** 2022,MPXV has posed a signiﬁcant threat to global public *** emergence of thousands of cases across the Western Hemisphere prompted the World Health Organization to declare an *** extensive coevolutionary history of poxviruses with humans has enabled these viruses to develop sophisticated mechanisms to counter the human immune ***ﬁcally,MPXV employs unique immune evasion strategies against a wide range of immunological elements,presenting a considerable challenge for treatment,especially following the discontinuation of routine smallpox vaccination among the general *** this review,we start by discussing the entry of the mpox virus and the onset of early infection,followed by an introduction to the mechanisms by which the mpox virus can evade the innate and adaptive immune *** caspase-1 inhibitory proteins and a PKR escape-related protein have been identiﬁed as phylogenomic hubs involved in modulating the immune environment during the MPXV *** respect to adaptive immunity,mpox viruses exhibit unique and exceptional T-cell inhibition capabilities,thereby comprehensively remodeling the host immune *** viral envelope also poses challenges for the neutralizing effects of antibodies and the complement *** unique immune evasion mechanisms employed by MPXV make novel multi-epitope and nucleic acid-based vaccines highly promising research directions worth ***,we brieﬂy discuss the impact of MPXV infection on immunosuppressed patients and the current status of MPXV vaccine *** review may provide valuable information for the development of new immunological treatments for mpox.

关键词： Immune response Immune evasion Mpox virus(MPXV) Immunopathology dna sensing

The Regulation of cGAS

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Virologica Sinica 2018年第2期33卷 117-124页

作者： Meiguang Xiong Suyun Wang Yan-Yi Wang Yong Ran Wuhan Institute of Virology Chinese Academy of Science

The cGAS-MITA pathway of cytosolic dna sensing plays essential roles in immune response against pathogens that contain dna or with dna production in their life cycles. The cGAS-MITA pathway also detects leaked or aberrant accumulated self dna in the cytoplasm under certain pathological conditions, such as virus induced cell death, dna damage, mitochondria damage, gene mutations, which results in autoimmune diseases. Therefore, the cGAS-MITA pathway must be tightly controlled to ensure proper immune response against pathogens and to avoid autoimmune diseases. The regulation of cGAS-MITA pathway at MITA-level have been extensively explored and reviewed elsewhere,here we provide a summary and perspective on recent advances in understanding of the cGAS regulation.

关键词： cGAS dna sensing Regulation Autoimmune

Viral evasion of dna-stimulated innate immune responses

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Cellular & Molecular Immunology 2017年第1期14卷 4-13页

作者： Maria H Christensen Sфren R Paludan Department of Biomedicine Aarhus University Aarhus DK-8000 Denmark Aarhus Research Center for Innate Immunology Aarhus University Aarhus DK-8000 Denmark

Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of dna sensing proteins, including cyclic GMP-AMP synthase （cGAS） and gamma-interferon- inducible protein （IFI16）, has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying dna genomes. The signaling stimulated by dna sensors depends on the adaptor protein STING （stimulator of interferon genes）, to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host dna sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.

关键词： dna sensing evasion innate immunology STING