Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase

Abstract

Human endogenous retrovirus W env (HERV-W env) plays a critical role in many neuropsychological diseases such as schizophrenia and multiple sclerosis (MS). These diseases are accompanied by immunological reactions in the central nervous system (CNS). Microglia are important immunocytes in brain inflammation that can produce a gasotransmitter-nitric oxide (NO). NO not only plays a role in the function of neuronal cells but also participates in the pathogenesis of various neuropsychological diseases. In this study, we reported increased NO production in CHME-5 microglia cells after they were transfected with HERV-W env. Moreover, HERV-W env increased the expression and function of human inducible nitric oxide synthase (hiNOS) and enhanced the promoter activity of hiNOS. Microglial migration was also enhanced. These data revealed that HERV-W env might contribute to increase NO production and microglial migration ability in neuropsychological disorders by regulating the expression of inducible NOS. Results from this study might lead to the identification of novel targets for the treatment of neuropsychological diseases, including neuroinflammatory diseases, stroke, and neurodegenerative diseases.

The human microglial HMC3 cell line: where do we stand? A systematic literature review

“…Interestingly, the CHME-5 cells were not able to sustain persistent huCV-OC43 infection, and responded to the acute infection with increased MMP activity and NO production [105]. In contrast to the HMC3/CHME3 aliquots, increased iNOS expression and NO production was detected also after overexpression of the endogenous retrovirus W envelope protein [88] and in response to a mixture of pro-inflammatory cytokines, including TNFα, IL-1β, and IFNγ [106]. Furthermore, the CHME-5 cells displayed increased arginase (ARG) activity in response to IL-4, which was significantly reduced by several antiretroviral drugs [106].…”

“…The cytoprotective effect induced by HIV infection was mediated by the HIV TAT protein and subsequent activation of survival signaling depending on the AKT pathway [82]. Since this initial observation, the human microglial CHME-5 cell line has been widely used to study the biology of HIV-1, as documented by more than 15 publications [83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98]. The CHME-5 cells were resistant to murine norovirus MV1 infection [99], whereas they were successfully used to culture Chlamydia pneumoniae isolated from post-mortem brain tissue of two patients affected by Alzheimer's disease [100].…”

Microglial Activation and Inflammation as a Factor in the Pathogenesis of Progressive Supranuclear Palsy (PSP)

“…Microglial cells are currently viewed as a relevant source of HERV proteins in the diseased brain. In this regard, it is worth mentioning that NO production and cellular migration were found to be affected in response to the stimulation of rat microglia with a recombinant HERV protein ( Xiao et al, 2017 ). Pathological processes that use the dopaminergic system have diverse clinical manifestations.…”

CKLF1 Enhances Inflammation-Mediated Carcinogenesis and Prevents Doxorubicin-Induced Apoptosis via IL6/STAT3 Signaling in HCC

“…Following incubation of 48 hours, the cells that had migrated through the membrane were fixed and stained with crystal violet and counted under a microscope (Olympus CH-40; ref. 19).…”