Tibetan PHD2D4E;C127S variant protects from viral diseases in hypoxia, but predispose to infections in normoxia via HIFα:IFN axis.

ABSTRACT: We previously reported that Tibetan-specific variant of prolyl-hydroxylase-2 (PHD2)D4E;C127S protects highlanders from hypoxia-triggered pathologies by destabilizing hypoxia-inducible factor (HIF)-1α. Others have reported that stabilized HIF1α negatively regulates interferon (IFN)-regulating factor (IRF)-3 under hypoxia. We examined the role of PHD2D4E;C127S variant in IFN synthesis in immune cells during viral infections. Primary monocytes and cells engineered to express the PHD2D4E;C127S variant displayed protection against dengue virus (DENV)-2 infection by suppressing HIF1α, in turn promoting IRF-3 and IFNα/β synthesis in hypoxia (3% O2) in vitro. However, under normoxia (21% O2), these mutant cells increased reactive oxygen species (ROS) generation following DENV2 infection. Increased

SUBMITTER: Ghosh R 

PROVIDER: S-EPMC12212868 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature