Understanding the Neurotrophic Virus Mechanisms and Their Potential Effect on Systemic Lupus Erythematosus Development

Figure 1. Infection with neurotrophic viruses leads to several conditions that alter the CNS. (A) The neurotrophic viruses mentioned (AdV, CMV, EV, EBV, HSV, LCMV, and SARS-CoV-2) can enter the CNS via potentially different ways; these include via the nasal epithelium, CSF, via hematogenous spread, through nerves, and/or immune cells. When these viruses interact with the CNS, microglia and astrocytes can secrete inflammatory cytokines, including TNF-α, IL-1β, IL-6, and CCL2. Activating this inflammatory process initiates a range of neurological disorders commonly observed across various types of viruses. (B) The presence of LCMV and CMV infections during pregnancy poses significant risks to the proper development of the fetus. Both viruses can cause congenital infections, leading to the improper development of the fetus’s central nervous system. Consequently, the newborn may experience significant long-term effects, such as behavioral or physiological abnormalities (Created by BioRender; License # RU26AQJL7Z).

Figure 2. CMV, EBV, and LMCV are potential effector agents in developing SLE and NPSLE. (A) Infection with CMV in patients who do not have a history of autoimmune diseases can induce the production of anti-nuclear antibodies, anti-dsDNA, anti-Sm/RNP, and anti-cardiolipin antibodies. Furthermore, such infection may decrease complement levels and induce proteinuria. Additionally, 11 CMV genes (UL32, UL36, UL44, UL50, UL56, UL82, UL84, UL95, UL105, UL117, and US31) have been observed in PBMCs from SLE patients, inducing inflammatory phenotypes. Moreover, in BALB/c mice, the administration of the pp65 CMV antigen induces the production of anti-chromatin, anti-centriole, anti-mitotic spindle type I/II (MSA I/II), and anti-dsDNA antibodies. (B) The EBV EBNA2 protein can modulate the CD40, LYST, JAZF1, IRF5, BLK, IKZF2, IL12RB2, FAM167A, PTPRC, and SLC15A genes. All of them are associated with the development of SLE. Moreover, LMP2A and EBNA1 proteins induce the production of anti-Sm and anti-dsDNA antibodies. (C) LCMV infection in the early stages in the C57BL/6 model produces the generation of autoantibodies, especially anti-chromatin and anti-Sm/RNP. (D) Infections triggered by CMV, EBV, and…