Endoplasmic reticulum-associated degradation potentiates the infectivity of influenza A virus by regulating the host redox state.

Endoplasmic reticulum-associated degradation potentiates the infectivity of influenza A virus by regulating the host redox state.
Free Radic Biol Med. 2019 Mar 21;:
Authors: Jung KI, Shin N, Ko DH, Pyo CW, Choi SY
Abstract
During influenza A virus (IAV) infection, significant effects of oxidative stress often emerge due to the disruption of the redox balance. Reactive oxygen species (ROS) generated during IAV infection have been known to exert various effects on both the virus and host tissue. However, the mechanisms underlying the accumulation of ROS and their physiological significance in IAV infection have been extensively studied but remain to be fully understood. Here, we show that the levels of Sp1, a key controller of Cu-Zn superoxide dismutase (SOD1) gene expression, and SOD1 are mainly dependent upon the activity of X-box-binding protein 1 (XBP1), which is a downstream factor of the endoplasmic reticulum (ER) transmembrane sensor inositol-requiring enzyme 1 (IRE1) during ER stress. In IRE1-deficient mouse embryo fibroblasts (MEFs) or A549 human lung cells treated with XBP1 siRNA, IAV-induced Sp1 loss was mitigated. However, overexpression of the spliced form of XBP1 in IRE1-deficient MEFs resulted in a further decrease in Sp1 levels, whereas the unspliced form showed no significant differences. Treatment with proteasome inhibitor MG132 markedly inhibited the IRE1/XBP1-mediated loss of Sp1 and SOD, suggesting the involvement ...

Source: Free Radical Biology and Medicine - March 20, 2019 Category: Biology Authors: Jung KI, Shin N, Ko DH, Pyo CW, Choi SY Tags: Free Radic Biol Med Source Type: research