8 26

Cited 0 times in

Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP

Authors
 Yeon-Mi Hong  ;  Seo Yeon Min  ;  Dayeong Kim  ;  Subin Kim  ;  Daekwan Seo  ;  Kyoung Hwa Lee  ;  Sang Hoon Han 
Citation
 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.23(5) : 2769, 2022-03 
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Issue Date
2022-03
MeSH
3' Untranslated Regions ; Cytomegalovirus / genetics ; Humans ; Immediate-Early Proteins* / genetics ; Latent Infection* ; MicroRNAs* / genetics ; MicroRNAs* / metabolism ; Serine / genetics ; Transcription Factor RelA / genetics
Keywords
HCMV ; MIEP ; NF-κB ; RelA/p65 ; immediate early protein ; latent infection ; microRNA ; phosphorylation ; serine 536
Abstract
Attenuating the expression of immediate early (IE) proteins is essential for controlling the lytic replication of human cytomegalovirus (HCMV). The human microRNAs (hsa-miRs), miR-200b-3p and miR-200c-3p, have been identified to bind the 3'-untranslated region (3'-UTR) of the mRNA encoding IE proteins. However, whether hsa-miRs can reduce IE72 expression and HCMV viral load or exhibit a crosstalk with the host cellular signaling machinery, most importantly the NF-κB cascade, has not been evaluated. In this study, argonaute-crosslinking and immunoprecipitation-seq revealed that miR-200b-3p and miR-200c-3p bind the 3'-UTR of UL123, which is a gene that encodes IE72. The binding of these miRNAs to the 3'-UTR of UL123 was verified in transfected cells stably expressing GFP. We used miR-200b-3p/miR-200c-3p mimics to counteract the downregulation of these miRNA after acute HCMV infection. This resulted in reduced IE72/IE86 expression and HCMV VL during lytic infection. We determined that IE72/IE86 alone can inhibit the phosphorylation of RelA/p65 at the Ser536 residue and that p-Ser536 RelA/p65 binds to the major IE promoter/enhancer (MIEP). The upregulation of miR-200b-3p and miR-200c-3p resulted in the phosphorylation of RelA/p65 at Ser536 through the downregulation of IE, and the binding of the resultant p-Ser536 RelA/p65 to MIEP resulted in a decreased production of pro-inflammatory cytokines. Overall, miR-200b-3p and miR-200c-3p-together with p-Ser536 RelA/p65-can prevent lytic HCMV replication during acute and latent infection.
Files in This Item:
T202200766.pdf Download
DOI
10.3390/ijms23052769
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Dayeong(김다영)
Lee, Kyoung Hwa(이경화) ORCID logo https://orcid.org/0000-0003-0033-1398
Han, Sang Hoon(한상훈) ORCID logo https://orcid.org/0000-0002-4278-5198
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188291
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links