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Original Article Issue
Lipoxygenase inhibits SFTSV replication by down-regulating autophagy
Military Medical Sciences 2025, 49(1): 27-34
Published: 25 January 2025
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Objective

To explore the effects of lipoxygenase (LOX) on severe fever with thrombocytopenia syndrome virus (SFTSV) in human umbilical vein endothelial cells (HUVECs).

Methods

The CCK-8 assay was used to assess the cytotoxicity of LOX in HUVECs. Real-time quantitative PCR (qPCR) was adopted to detect the replication of viral RNA in cells. The infection rate of SFTSV to HUVECs was observed via indirect immunofluorescence assay (IFA). The expressions of intracellular viral NP protein and autophagy related proteins microtubule-associated protein 1 light chain 3 (LC3) and adenosine 5’-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) were detected via Western blotting. Lipid metabolomics was used to analyze the differences in expressions of intracellular metabolites in the SFTSV-infected Huh 7 with or without LOX treatment.

Results

The results of CCK-8 showed no obvious cytotoxicity to HUVECs with LOX≤8 mg/mL. With the increase of LOX concentrations, the viral RNA level, viral infection rate, and expressions of SFTSV nucleoproteind (NP) protein were gradually decreased, respectively. The autophagy reaction was activated in SFTSV-infected HUVECs, evidenced by the increased expression level of LC3 Ⅱ protein. Compared with the untreated group, LOX treatment resulted in decreased levels of LC3 Ⅱ and AMPK phosphorylation, and enhanced phosphorylation of mTOR in SFTSV-infected HUVEC.

Conclusion

LOX negatively regulates autophagy by inhibiting AMPK/mTOR signaling pathway, thereby inhibiting SFTSV replication.

Open Access Editorial Issue
Bracing the artificial intelligence technology in viral infectious disease control
Infectious Medicine 2025, 4(2): 100186
Published: 01 June 2025
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Open Access Review Issue
Epidemiology, clinical characteristics, and treatment of severe fever with thrombocytopenia syndrome
Infectious Medicine 2022, 1(1): 40-49
Published: 10 January 2022
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Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by a novel phlebovirus (SFTS virus, SFTSV) in the family Phenuiviridae of the order Bunyavirales. The disease causes a wide spectrum of clinical signs and symptoms, ranging from mild febrile disease accompanied by thrombocytopenia and/or leukocytopenia to hemorrhagic fever, encephalitis, multiple organ failure, and death. SFTS was first identified in China and was subsequently reported in South Korea and Japan. The case-fatality rate ranges from 2.7% to 45.7%. Older age has been consistently shown to be the most important predictor of adverse disease outcomes. Older age exacerbates disease mainly through dysregulation of host immune cells and uncontrolled inflammatory responses. Tick-to-human transmission is the primary route of human infection with SFTSV, and Haemaphysalis longicornis is the primary tick vector of SFTSV. Despite its high case-fatality rate, vaccines and antiviral therapies for SFTS are not currently available. The therapeutic efficacies of several antiviral agents against SFTSV are currently being evaluated. Ribavirin was initially identified as a potential antiviral therapy for SFTS but was subsequently found to inefficiently improve disease outcomes, especially among patients with high viral loads. Favipiravir (T705) decreased both time to clinical improvement and mortality when administered early in patients with low viral loads. Anti-inflammatory agents including corticosteroids have been proposed to play therapeutic roles. However, the efficacy of other therapeutic modalities, such as convalescent plasma, is not yet clear.

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