RRC ID 85885
Author Hirai M, Amaliin K, Huang JR, Aktar S, Mori Y, Arii J.
Title HHV-6B ribonucleotide reductase sequesters NF-κB subunit p65 to inhibit innate immune responses.
Journal iScience
Abstract Human herpesvirus 6B (HHV-6B) belongs to the genus Roseolovirus of the betaherpesvirus subfamily, causing exanthema subitum and encephalitis. Although viral ribonucleotide reductase (RNR) is conserved in betaherpesviruses, it has lost its enzymatic activity. Human cytomegalovirus (HCMV) belongs to the other betaherpesvirus genus, Cytomegalovirus; its RNR inhibits nuclear factor-kappa B (NF-κB) signaling via interaction with the adaptor molecule RIPK1. However, the significance of enzymatically inactive RNR in roseoviruses is unclear. Here, we show that the RNRs from all three human roseoloviruses inhibit NF-κB activation. HHV-6B RNR sequesters NF-κB subunit p65 in the cytoplasm and inhibits its translocation into the nucleus. Silencing HHV-6B RNR increased the expression of inflammatory molecules in infected cells. This study reveals that inhibiting NF-κB is a conserved role of the RNR in betaherpesviruses but that the precise mechanisms responsible for these effects are different.
Volume 28(2)
Pages 111710
Published 2024-1-1
DOI 10.1016/j.isci.2024.111710
PII S2589-0042(24)02937-7
PMID 39877902
PMC PMC11772975
IF 4.447
Resource
Cord blood stem cells for research