PMID- 37503036
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231129
DP  - 2023 Jul 23
TI  - KSHV vIL-6 Enhances Inflammatory Responses by Epigenetic Reprogramming.
LID - 2023.06.25.546454 [pii]
LID - 10.1101/2023.06.25.546454 [doi]
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) inflammatory cytokine syndrome 
      (KICS) is a newly described chronic inflammatory disease condition caused by KSHV 
      infection and is characterized by high KSHV viral load and sustained elevations 
      of serum KSHV-encoded IL-6 (vIL-6) and human IL-6 (hIL-6). KICS has significant 
      immortality and possesses greater risks of having other complications, which 
      include malignancies. Although prolonged inflammatory vIL-6 exposure by 
      persistent KSHV infection is expected to have key roles in subsequent disease 
      development, the biological effects of prolonged vIL-6 exposure remain elusive. 
      Using thiol-Linked Alkylation for the Metabolic Sequencing and Cleavage Under 
      Target & Release Using Nuclease analysis, we studied the effect of prolonged 
      vIL-6 exposure in chromatin landscape and resulting cytokine production. The 
      studies showed that prolonged vIL-6 exposure increased Bromodomain containing 4 
      (BRD4) and histone H3 lysine 27 acetylation co-occupancies on chromatin, and the 
      recruitment sites were frequently co-localized with poised RNAPII with associated 
      enzymes. Increased BRD4 recruitment on promoters was associated with increased 
      and prolonged NF-kappaB p65 binding after the lipopolysaccharide stimulation. The p65 
      binding resulted in quicker and sustained transcription bursts from the 
      promoters; this mechanism increased total amounts of hIL-6 and IL-10 in tissue 
      culture. Pretreatment with the BRD4 inhibitor, OTX015, eliminated the enhanced 
      inflammatory cytokine production. These findings suggest that persistent vIL-6 
      exposure may establish a chromatin landscape favorable for the reactivation of 
      inflammatory responses in monocytes. This epigenetic memory may explain the 
      greater risk of chronic inflammatory disease development in KSHV-infected 
      individuals.
FAU - Inagaki, Tomoki
AU  - Inagaki T
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
FAU - Wang, Kang-Hsin
AU  - Wang KH
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
FAU - Kumar, Ashish
AU  - Kumar A
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
FAU - Izumiya, Chie
AU  - Izumiya C
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
FAU - Miura, Hiroki
AU  - Miura H
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
FAU - Komaki, Somayeh
AU  - Komaki S
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
FAU - Davis, Ryan R
AU  - Davis RR
AD  - Department of Pathology and Laboratory Medicine, School of Medicine, UC Davis, 
      Sacramento, California USA.
FAU - Tepper, Clifford G
AU  - Tepper CG
AD  - Department of Biochemistry and Molecular Medicine, School of Medicine, UC Davis, 
      Sacramento, California USA.
FAU - Katano, Harutaka
AU  - Katano H
AD  - Department of Pathology, National Institute of Infectious Diseases, Shinjuku, 
      Tokyo, Japan.
FAU - Shimoda, Michiko
AU  - Shimoda M
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
FAU - Izumiya, Yoshihiro
AU  - Izumiya Y
AD  - Department of Dermatology, School of Medicine, the University of California Davis 
      (UC Davis), Sacramento, California USA.
AD  - Department of Biochemistry and Molecular Medicine, School of Medicine, UC Davis, 
      Sacramento, California USA.
LA  - eng
GR  - P30 CA093373/CA/NCI NIH HHS/United States
GR  - R01 CA232845/CA/NCI NIH HHS/United States
GR  - R01 AI167663/AI/NIAID NIH HHS/United States
GR  - R01 CA225266/CA/NCI NIH HHS/United States
GR  - R21 AI155515/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20230723
PL  - United States
TA  - bioRxiv
JT  - bioRxiv : the preprint server for biology
JID - 101680187
UIN - PLoS Pathog. 2023 Nov 7;19(11):e1011771. PMID: 37934757
PMC - PMC10370004
EDAT- 2023/07/28 06:42
MHDA- 2023/07/28 06:43
PMCR- 2023/07/26
CRDT- 2023/07/28 04:25
PHST- 2023/07/28 06:42 [pubmed]
PHST- 2023/07/28 06:43 [medline]
PHST- 2023/07/28 04:25 [entrez]
PHST- 2023/07/26 00:00 [pmc-release]
AID - 2023.06.25.546454 [pii]
AID - 10.1101/2023.06.25.546454 [doi]
PST - epublish
SO  - bioRxiv [Preprint]. 2023 Jul 23:2023.06.25.546454. doi: 
      10.1101/2023.06.25.546454.