Stress response contributes to autonomous immune responses. Many stresses
including infection induce integrated stress response (ISR). ISR is mediated by a set of
kinases PKR, PERK, HRI, and GCN2. Viral dsRNA activates PKR. Viral proteins are
produced in the endoplasmic reticulum and may cause ER stress, which activates
PERK. Infection also can cause iron deficiency sensed by HRI kinase and amino acid
shortage sensed by GCN2. The arrest of translation caused by ISR inhibits viral
replication and activates NFkB, a major regulator of immunity. Therefore, ISR acts as
an immunodefense mechanism. Other stress responses that contribute to immune
defense include unfolded protein response (UPR). UPR activates degradation of ERassociated
mRNAs and proteins including viral ones. DNA damage response leads to
NFkB activation, and so does oxidative stress through various mechanisms. The major
stress response factor p53 has anti-viral activity. Autophagy activated by many stresses
also plays a role in immunodefense by degrading intracellular pathogens.
Keywords: DNA damage response, ERAD, Homeostasis, Immune response,
Integrated stress response, NLRP3 inflammasome, Nrf2, Oxidative stress, RIDD,
Unfolded protein response, Xenophagy.
