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Background: Genetically polymorphic Superoxide Dismutase 1 G93A (SOD1-G93A) underlies one form of familial Amyotrophic Lateral Sclerosis (ALS). Exposures from viruses may also contribute to ALS, possibly by stimulating immune factors, such as IL-6, Interferon Stimulated Genes, and Nitric Oxide. Recently, chlorovirus ATCV-1, which encodes a SOD1, was shown to replicate in macrophages and induce inflammatory factors. Objective: This study aimed to determine if ATCV-1 influences development of motor degeneration in an ALS mouse model and to assess whether SOD1 of ATCV-1 influences production of inflammatory factors from macrophages. Methods: Sera from sporadic ALS patients were screened for antibody to ATCV-1. Active or inactivated ATCV-1, saline, or a viral mimetic, polyinosinic:polycytidylic acid (poly I:C) were injected intracranially into transgenic mice expressing human SOD1-G93A- or C57Bl/6 mice. RAW264.7 mouse macrophage cells were transfected with a plasmid vector expressing ATCV-1 SOD1 or an empty vector prior to stimulation with poly I:C with or without Interferon-gamma (IFN-γ). Results: Serum from sporadic ALS patients had significantly more IgG1 antibody directed against ATCV-1 than healthy controls. Infection of SOD1-G93A mice with active ATCV-1 significantly accelerated onset of motor loss, as measured by tail paralysis, hind limb tucking, righting reflex, and latency to fall in a hanging cage-lid test, but did not significantly affect mortality when compared to saline-treated transgenics. By contrast, poly I:C treatment significantly lengthened survival time but only minimally slowed onset of motor loss, while heat-inactivated ATCV-1 did not affect motor loss or survival. ATCV-1 SOD1 significantly increased expression of IL-6, IL-10, ISG promoter activity, and production of Nitric Oxide from RAW264.7 cells. Conclusion: ATCV-1 chlorovirus encoding an endogenous SOD1 accelerates pathogenesis but not mortality, while poly I:C that stimulates antiviral immune responses delays mortality in an ALS mouse model. ATCV-1 SOD1 enhances induction of inflammatory factors from macrophages. [ABSTRACT FROM AUTHOR]

BackgroundGenetically polymorphic Superoxide Dismutase 1 G93A (SOD1-G93A) underlies one form of familial Amyotrophic Lateral Sclerosis (ALS). Exposures from viruses may also contribute to ALS, possibly by stimulating immune factors, such as IL-6, Interferon Stimulated Genes, and Nitric Oxide. Recently, chlorovirus ATCV-1, which encodes a SOD1, was shown to replicate in macrophages and induce inflammatory factors.ObjectiveThis study aimed to determine if ATCV-1 influences development of motor degeneration in an ALS mouse model and to assess whether SOD1 of ATCV-1 influences production of inflammatory factors from macrophages.MethodsSera from sporadic ALS patients were screened for antibody to ATCV-1. Active or inactivated ATCV-1, saline, or a viral mimetic, polyinosinic:polycytidylic acid (poly I:C) were injected intracranially into transgenic mice expressing human SOD1-G93A- or C57Bl/6 mice. RAW264.7 mouse macrophage cells were transfected with a plasmid vector expressing ATCV-1 SOD1 or an empty vector prior to stimulation with poly I:C with or without Interferon-gamma (IFN-γ).ResultsSerum from sporadic ALS patients had significantly more IgG1 antibody directed against ATCV-1 than healthy controls. Infection of SOD1-G93A mice with active ATCV-1 significantly accelerated onset of motor loss, as measured by tail paralysis, hind limb tucking, righting reflex, and latency to fall in a hanging cage-lid test, but did not significantly affect mortality when compared to saline-treated transgenics. By contrast, poly I:C treatment significantly lengthened survival time but only minimally slowed onset of motor loss, while heat-inactivated ATCV-1 did not affect motor loss or survival. ATCV-1 SOD1 significantly increased expression of IL-6, IL-10, ISG promoter activity, and production of Nitric Oxide from RAW264.7 cells.ConclusionATCV-1 chlorovirus encoding an endogenous SOD1 accelerates pathogenesis but not mortality, while poly I:C that stimulates antiviral immune responses delays mortality in an ALS mouse model. ATCV-1 SOD1 enhances induction of inflammatory factors from macrophages.

The Chlorovirus genus of the Phycodnaviridae family includes large viruses with a double-stranded DNA genome. Chloroviruses are widely distributed in freshwater bodies around the world and have been isolated from freshwater sources in Europe, Asia, Australia, and North and South America. One representative of chloroviruses is Acanthocystis turfacea chlorella virus 1 (ATCV-1), which is hosted by Chlorella heliozoae. A few publications in the last ten years about the potential effects of ATCV-1 on the human brain sparked interest among specialists in the field of human infectious pathology. The goal of our viewpoint was to compile the scant research on the effects of ATCV-1 on the human body, to demonstrate the role of chloroviruses as new possible infectious agents for human health, and to indicate potential routes of virus transmission. We believe that ATCV-1 transmission routes remain unexplored. We also question whether chlorella-based nutritional supplements are dangerous for ATCV-1 infections. Further research will help to identify the routes of infection, the cell types in which ATCV-1 can persist, and the pathological mechanisms of the virus’s effect on the human body.

Summary of main observation and conclusion: The N‐glycans attached to some chloroviruses comprise a hyperbranched core structure without precedent. We are interested in the chemical synthesis of the hexasaccharide attached to ATCV‐1 (Acanthocystis turfacea Chlorella virus 1) for its distinct structure. After exploring four routes, the target hexasaccharide 2 was successfully synthesized for the first time in overall 10% yield over 8 steps from thioglycoside building blocks. This synthetic protocol is characterized by the three‐component one‐pot glycosylation and the regioselective glycosylation reactions. The disclosed synthetic approach to this new type of N‐glycans will facilitate the in‐depth understanding of their biological functions. A highly branched hexasaccharide was successfully synthesized by the three‐component preactivation‐based one‐pot glycosylation and the regioselective glycosylation reactions for the first time. [ABSTRACT FROM AUTHOR]

The Chlorovirus genus of the Phycodnaviridae family includes large viruses with a double-stranded DNA genome. Chloroviruses are widely distributed in freshwater bodies around the world and have been isolated from freshwater sources in Europe, Asia, Australia, and North and South America. One representative of chloroviruses is Acanthocystis turfacea chlorella virus 1 (ATCV-1), which is hosted by Chlorella heliozoae . A few publications in the last ten years about the potential effects of ATCV-1 on the human brain sparked interest among specialists in the field of human infectious pathology. The goal of our viewpoint was to compile the scant research on the effects of ATCV-1 on the human body, to demonstrate the role of chloroviruses as new possible infectious agents for human health, and to indicate potential routes of virus transmission. We believe that ATCV-1 transmission routes remain unexplored. We also question whether chlorella-based nutritional supplements are dangerous for ATCV-1 infections. Further research will help to identify the routes of infection, the cell types in which ATCV-1 can persist, and the pathological mechanisms of the virus's effect on the human body.