Cholesterol 25-hydroxylase inhibits Newcastle disease virus replication by enzyme activity-dependent and direct interaction with nucleocapsid protein

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Newcastle disease virus (NDV) is a significant enveloped within the Paramyxoviridae family, posing major threat to global poultry industry. Increasing evidence suggests that cholesterol-25-hydroxylase (CH25H) and its enzymatic product, 25-hydroxycholesterol (25HC), exhibit broad-spectrum antiviral activity properties by modulating lipid metabolism various signaling pathways. However, specific role of CH25H in regulating NDV infection replication remains unclear. In this study, we demonstrate significantly inhibits blocking viral entry through 25HC. Notably, catalytic mutant (CH25H-M), which lacks hydroxylase activity, still retains partial ability inhibit replication, suggesting involvement an enzyme-independent mechanism. Furthermore, found interacts with nucleoprotein (NP), leading reduction NP expression inhibition ribonucleoprotein (RNP) complex activity. These findings reveal exerts effects both enzyme-dependent -independent mechanisms, providing new insights into host defense offering potential targets for development therapies. IMPORTANCE Cholesterol 25-hydroxylase multifunctional protein has been implicated life cycles viruses. As prototype paramyxovirus, poses industry, causing substantial economic losses. Uncovering mechanisms NDV-host interactions crucial unraveling pathogenesis immune response, can drive effective Here, CH25H, whose induced upon infection, plays pivotal restricting replication. Specifically, RNP expand our understanding CH25H’s functions offer virus-host interactions, novel drugs against related pathogens.

Language: Английский

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The role of lipids and lipids lowering drugs in human papillomavirus (HPV) and HPV-associated cancers

Infectious Agents and Cancer, Journal Year: 2025, Volume and Issue: 20(1)

Published: Jan. 28, 2025

Both women and men are now confronted with the grave threat of cancers caused by human papillomavirus (HPV). It is estimated that 80% may encounter HPV over their lives. In preponderance cases involving anal, head neck, oral, oropharyngeal, penile, vaginal, vulvar, cervical malignancies, high-risk (HR-HPV) causative agent. 2019, believed to have been cause 620,000 new cancer in 70,000 worldwide. The bulk 530,000 (~ 270,000 fatalities) infection (86% cases, 88% deaths) happen poor nations each year. Lipid metabolism crucial development related HPV. One most noticeable metabolic abnormalities lipid reprogramming, which cells dysregulate obtain sufficient energy, building blocks for cell membranes, signaling molecules necessary invasion, metastasis, proliferation, survival. Moreover, proteins' stimulation production infected will probably a significant effect on oncogenesis. addition, lipids critical producing cellular epithelial-mesenchymal transition (EMT) process, therapy resistance HPV-related (HRCs). Therefore, essential HRC also be an important target approaches associated treatments during or development. This review study looked at role lipid-lowering drugs cancers.

Language: Английский

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CH25H/25-HC promotes pulmonary fibrosis via AMPK/STAT6 pathway-dependent M2 macrophage polarization in COPD

Immunobiology, Journal Year: 2025, Volume and Issue: 230(3), P. 152908 - 152908

Published: April 25, 2025

Chronic obstructive pulmonary disease (COPD) is intricately linked to fibrosis, yet the underlying mechanisms remain unclear. This study investigates whether CH25H/25-hydroxycholesterol (25-HC) promotes fibrosis in COPD by modulating AMPK/STAT6-dependent M2 macrophage polarization. Using GEO datasets and a cigarette smoke-induced mouse model, we analyzed CH25H expression fibrotic pathology. was silenced via adeno-associated virus (AAV)-delivered shRNA. Histopathology, flow cytometry, qPCR, Western blotting assessed polarization (M1/M2), AMPK/STAT6 pathway activity. Bone marrow-derived macrophages (BMDMs) were employed validate mechanisms. The role of investigated using specific activator. Analysis database experimental verification showed significantly increased both lung tissues from mice. knockdown alleviated alveolar damage, airway remodeling, mice, evidenced reduced fibrosis-related proteins, improved function, attenuated inflammatory responses. Moreover, inhibited decreased proportion M2-type macrophages. Importantly, levels 25-HC following asso ciated with suppressed activation pathway. Rescue experiments demonstrated that protective effects could be reversed adding AMPKα activator GSK621. Our findings demonstrate CH25H/25-HC exacerbates COPD-associated promoting Targeting may represent novel therapeutic strategy for mitigating COPD.

Language: Английский

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The role of cholesterol 25-hydroxylase in viral infections: Mechanisms and implications

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 249, P. 154783 - 154783

Published: Aug. 24, 2023

Language: Английский

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