Central Zika virus infection causes hypothalamic inflammation and persistent insulin resistance in adult mice.

ABSTRACT: Zika virus (ZIKV) is a neurotropic flavivirus capable of infecting the adult brain, however its impact on hypothalamic function and metabolic regulation remains unclear. Here, we show that ZIKV invades the hypothalamus of immunocompetent adult mice, where it replicates and persists, leading to sustained insulin resistance. Following infection, ZIKV RNA and negative strand were detected in the hypothalamus of mice and immunostaining confirmed viral proteins in neurons, especially POMC-positive cells. At 6 dpi, ZIKV induced hypothalamic neuroinflammation, as shown by the upregulation of TNF-α, IL-6, IFN-β, and ISG-15, as well as microglial activation. These inflammatory responses were associated with impaired insulin signaling, characterized by reduced phosphorylation of IRS-1 and S6K, downr

SUBMITTER: de Lima EV 

PROVIDER: S-EPMC12518652 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature