Human endogenous retrovirus W family envelope protein (HERV-W env) facilitates the production of TNF-α and IL-10 by inhibiting MyD88s in glial cells

• Published in: Archives of virology 2021-04, Vol.166 (4), p.1035-1045
• Main Authors: Wang, Xiuling, Wu, Xiulin, Huang, Jin, Li, Haiyan, Yan, Qiujin, Zhu, Fan
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cell Line, Tumor; Endogenous Retroviruses - metabolism; Gene Products, env - metabolism; Glial cells; Humans; Infectious Diseases; Inflammation; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - metabolism; Medical Microbiology; Mental disorders; Molecular modelling; mRNA; Multiple sclerosis; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Neuroglia - immunology; Neuroglia - metabolism; Neurological diseases; Original Article; Proteins; RNA, Messenger - metabolism; Schizophrenia; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Viral envelope proteins; Virology
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-020-04933-8

Human endogenous retrovirus W family envelope protein (HERV-W env) is associated with several neurological and psychiatric disorders, including multiple sclerosis (MS) and schizophrenia. Clinical studies have demonstrated a common link between inflammatory abnormalities and HERV-W env in neuropsychiatric diseases. Nonetheless, the molecular mechanisms by which HERV-W env mediates neuroinflammation are still unclear. In this study, we found that HERV-W env significantly increased the mRNA and protein levels of TNF-α and IL-10 in U251 and A172 cells. HERV-W env also induced a notable increase in Toll-like receptor 4 (TLR4). Knockdown of TLR4 impaired the expressions of TNF-α and IL-10 induced by HERV-W env. Overexpression of HERV-W env led to the upregulation of MyD88 but caused a decrease in MyD88s. MyD88s overexpression suppressed the expressions of TNF-α and IL-10 induced by HERV-W env. These findings indicate that HERV-W env upregulates the expressions of IL-10 and TNF-α by inhibiting the production of MyD88s in glial cells. This work sheds light on the immune pathogenesis of HERV-W env in neuropsychiatric disorders.