PMID- 23720728 OWN - NLM STAT- MEDLINE DCOM- 20130918 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 87 IP - 15 DP - 2013 Aug TI - Constitutive interferon-inducible protein 16-inflammasome activation during Epstein-Barr virus latency I, II, and III in B and epithelial cells. PG - 8606-23 LID - 10.1128/JVI.00805-13 [doi] AB - Epstein-Barr virus (EBV), etiologically linked with human B-cell malignancies and nasopharyngeal carcinoma (NPC), establishes three types of latency that facilitate its episomal genome persistence and evasion of host immune responses. The innate inflammasome responses recognize the pathogen-associated molecular patterns which lead into the association of a cytoplasmic sensor such as NLRP3 and AIM2 proteins or nuclear interferon-inducible protein 16 (IFI16) with adaptor ASC protein (apoptosis-associated speck-like protein with a caspase recruitment domain) and effector procaspase-1, resulting in active caspase-1 formation which cleaves the proforms of inflammatory interleukin-1beta (IL-1beta), IL-18, and IL-33 cytokines. Whether inflammasome responses recognize and respond to EBV genome in the nuclei was not known. We observed evidence of inflammasome activation, such as the activation of caspase-1 and cleavage of pro-IL-1beta, -IL-18, and -IL-33, in EBV latency I Raji cells, latency II NPC C666-1 cells, and latency III lymphoblastoid cell lines (LCL). Interaction between ASC with IFI16 but not with AIM2 or NLRP3 was detected in all three latencies and during EBV infection of primary human B cells. IFI16 and cleaved caspase-1, IL-1beta, IL-18, and IL-33 were detected in the exosomes from Raji cells and LCL. Though EBV nuclear antigen 1 (EBNA1) and EBV-encoded small RNAs (EBERs) are common to all forms of EBV latency, caspase-1 cleavage was not detected in cells expressing EBNA1 alone, and blocking EBER transcription did not inhibit caspase-1 cleavage. In fluorescence in situ hybridization (FISH) analysis, IFI16 colocalized with the EBV genome in LCL and Raji cell nuclei. These studies demonstrated that constant sensing of latent EBV genome by IFI16 in all types of latency results in the constitutive induction of the inflammasome and IL-1beta, IL-18, and IL-33 maturation. FAU - Ansari, Mairaj Ahmed AU - Ansari MA AD - H. M. Bligh Cancer Research Laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois USA. FAU - Singh, Vivek Vikram AU - Singh VV FAU - Dutta, Sujoy AU - Dutta S FAU - Veettil, Mohanan Valiya AU - Veettil MV FAU - Dutta, Dipanjan AU - Dutta D FAU - Chikoti, Leela AU - Chikoti L FAU - Lu, Jie AU - Lu J FAU - Everly, David AU - Everly D FAU - Chandran, Bala AU - Chandran B LA - eng GR - CA 168472/CA/NCI NIH HHS/United States GR - R01 CA075911/CA/NCI NIH HHS/United States GR - R01 CA180758/CA/NCI NIH HHS/United States GR - R01 CA168472/CA/NCI NIH HHS/United States GR - CA 075911/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130529 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (IL33 protein, human) RN - 0 (Inflammasomes) RN - 0 (Interleukin-18) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-33) RN - 0 (Interleukins) RN - 0 (Nuclear Proteins) RN - 0 (Phosphoproteins) RN - 148998-64-5 (IFI16 protein, human) SB - IM EIN - J Virol. 2017 Nov 14;91(23 ):. PMID: 29138330 MH - B-Lymphocytes/*immunology/virology MH - Cells, Cultured MH - Epithelial Cells/*immunology/virology MH - Herpesvirus 4, Human/*immunology/*physiology MH - Humans MH - Hydrolysis MH - Inflammasomes/*metabolism MH - Interleukin-18/metabolism MH - Interleukin-1beta/metabolism MH - Interleukin-33 MH - Interleukins/metabolism MH - Nuclear Proteins/*metabolism MH - Phosphoproteins/*metabolism MH - *Virus Latency PMC - PMC3719826 EDAT- 2013/05/31 06:00 MHDA- 2013/09/21 06:00 PMCR- 2014/02/01 CRDT- 2013/05/31 06:00 PHST- 2013/05/31 06:00 [entrez] PHST- 2013/05/31 06:00 [pubmed] PHST- 2013/09/21 06:00 [medline] PHST- 2014/02/01 00:00 [pmc-release] AID - JVI.00805-13 [pii] AID - 00805-13 [pii] AID - 10.1128/JVI.00805-13 [doi] PST - ppublish SO - J Virol. 2013 Aug;87(15):8606-23. doi: 10.1128/JVI.00805-13. Epub 2013 May 29.