Herpes Simplex Virus ICP27 Protein Inhibits AIM 2-Dependent Inflammasome Influencing Pro-Inflammatory Cytokines Release in Human Pigment Epithelial Cells (hTert-RPE 1)

被引:0
作者
Caproni, Anna [1 ]
Nordi, Chiara [1 ]
Fontana, Riccardo [1 ]
Facchini, Martina [1 ]
Melija, Sara [1 ]
Pappada, Mariangela [1 ]
Buratto, Mattia [1 ]
Marconi, Peggy [1 ,2 ]
机构
[1] Univ Ferrara, Dept Chem Pharmaceut & Agr Sci, I-44121 Ferrara, Italy
[2] LTTA Lab Adv Therapies, Technopole Ferrara, I-44121 Ferrara, Italy
关键词
viruses; host-virus interaction; innate immunity; inflammasome; NF-KAPPA-B; ACTIVATION; INNATE; EXPRESSION; DNA; INDUCTION; INFECTION; CASPASE-1; APOPTOSIS; SUSCEPTIBILITY;
D O I
10.3390/ijms25094608
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although Herpes simplex virus type 1 (HSV-1) has been deeply studied, significant gaps remain in the fundamental understanding of HSV-host interactions: our work focused on studying the Infected Cell Protein 27 (ICP27) as an inhibitor of the Absent-in-melanoma-2 (AIM 2) inflammasome pathway, leading to reduced pro-inflammatory cytokines that influence the activation of a protective innate immune response to infection. To assess the inhibition of the inflammasome by the ICP27, hTert-immortalized Retinal Pigment Epithelial cells (hTert-RPE 1) infected with HSV-1 wild type were compared to HSV-1 lacking functional ICP27 (HSV-1 triangle ICP27) infected cells. The activation of the inflammasome by HSV-1 triangle ICP27 was demonstrated by quantifying the gene and protein expression of the inflammasome constituents using real-time PCR and Western blot. The detection of the cleavage of the pro-caspase-1 into the active form was performed by using a bioluminescent assay, while the quantification of interleukins 1 beta (IL-1 beta) and 18 (IL-18)released in the supernatant was quantified using an ELISA assay. The data showed that the presence of the ICP27 expressed by HSV-1 induces, in contrast to HSV-1 triangle ICP27 vector, a significant downregulation of AIM 2 inflammasome constituent proteins and, consequently, the release of pro-inflammatory interleukins into the extracellular environment reducing an effective response in counteracting infection.
引用
收藏
页数:20
相关论文
共 92 条
[11]   HSV-1 ICP27 targets the TBK1-activated STING signalsome to inhibit virus-induced type I IFN expression [J].
Christensen, Maria H. ;
Jensen, Soren B. ;
Miettinen, Juho J. ;
Luecke, Stefanie ;
Prabakaran, Thaneas ;
Reinert, Line S. ;
Mettenleiter, Thomas ;
Chen, Zhijian J. ;
Knipe, David M. ;
Sandri-Goldin, Rozanne M. ;
Enquist, Lynn W. ;
Hartmann, Rune ;
Mogensen, Trine H. ;
Rice, Stephen A. ;
Nyman, Tuula A. ;
Matikainen, Sampsa ;
Paludan, Soren R. .
EMBO JOURNAL, 2016, 35 (13) :1385-1399
[12]   Control of innate and adaptive immunity by the inflammasome [J].
Ciraci, Ceren ;
Janczy, John R. ;
Sutterwala, Fayyaz S. ;
Cassel, Suzanne L. .
MICROBES AND INFECTION, 2012, 14 (14) :1263-1270
[13]   Transcriptional Regulation of Inflammasomes [J].
Cornut, Maxence ;
Bourdonnay, Emilie ;
Henry, Thomas .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (21)
[14]   The Intersection of Innate Immune Pathways with the Latent Herpes Simplex Virus Genome [J].
Cuddy, Sean R. ;
Cliffe, Anna R. .
JOURNAL OF VIROLOGY, 2023, 97 (05)
[15]   Inflammasome: structure, biological functions, and therapeutic targets [J].
Dai, Yali ;
Zhou, Jing ;
Shi, Chunmeng .
MEDCOMM, 2023, 4 (05)
[16]   Mucosal immunology of the ocular surface [J].
de Paiva, Cintia S. ;
St Leger, Anthony J. ;
Caspi, Rachel R. .
MUCOSAL IMMUNOLOGY, 2022, 15 (06) :1143-1157
[17]   Targeting Inflammasome Activation in Viral Infection: A Therapeutic Solution? [J].
Deng, Chuan-Han ;
Li, Tian-Qi ;
Zhang, Wei ;
Zhao, Qi ;
Wang, Ying .
VIRUSES-BASEL, 2023, 15 (07)
[18]   AIM2 inflammasome is activated by pharmacological disruption of nuclear envelope integrity [J].
Di Micco, Antonia ;
Frera, Gianluca ;
Lugrin, Jerome ;
Jamilloux, Yvan ;
Hsu, Erh-Ting ;
Tardivel, Aubry ;
De Gassart, Aude ;
Zaffalon, Lea ;
Bujisic, Bojan ;
Siegert, Stefanie ;
Quadroni, Manfredo ;
Broz, Petr ;
Henry, Thomas ;
Hrycyna, Christine A. ;
Martinon, Fabio .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (32) :E4671-E4680
[19]   An extended set of PRDM1/BLIMP1 target genes links binding motif type to dynamic repression [J].
Doody, Gina M. ;
Care, Matthew A. ;
Burgoyne, Nicholas J. ;
Bradford, James R. ;
Bota, Maria ;
Bonifer, Constanze ;
Westhead, David R. ;
Tooze, Reuben M. .
NUCLEIC ACIDS RESEARCH, 2010, 38 (16) :5336-5350
[20]  
Fraefel C, 2011, METHODS MOL BIOL, V737, P303, DOI 10.1007/978-1-61779-095-9_13