SAMHD1 silencing cooperates with radiotherapy to enhance anti-tumor immunity through IFI16-STING pathway in lung adenocarcinoma

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Дек. 29, 2022

Abstract Background Sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (SAMHD1) is a DNA end resection factor, which involved in damage repair innate immunity. However, the role of SAMHD1 anti-tumor immunity still unknown. This study investigated effects on stimulator interferon genes (STING)-type I (IFN) pathway radiation-induced immune responses. Methods The roles activation cytosolic sensing STING lung adenocarcinoma (LUAD) cells were with flow cytometry, immunofluorescence, immunoblotting qPCR. combined silencing radiation tumor cell growth also evaluated colony formation CCK8 assay. Lewis cancer mouse model was used to evaluate efficiency radiotherapy vivo. Macrophage M1 polarization cytotoxic T infiltration cytometry. Results single-stranded (ssDNA) accumulated cytosol SAMHD1-deficient cells, accompanied by upregulated sensor IFN-γ-inducible 16 (IFI16) activated pathway. translocation IFI16 from nucleus detected cells. acquired STING-IFN-I LUAD promoted macrophage vitro. synergized activate ssDNA-STING-IFN-I pathway, inhibit proliferation, promote apoptosis regulate cycle. cooperated increase CD86 + MHC-II high proportion CD8 Conclusions deficiency induced IFN-I production through IFI16-STING Moreover, downregulation enhance responses infiltration. Combination inhibition may be potentially therapeutic strategy for patients.

Язык: Английский

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Foot-and-mouth disease virus downregulates vacuolar protein sorting 28 to promote viral replication

Journal of Virology, Год журнала: 2023, Номер 97(8)

Опубликована: Авг. 11, 2023

Vacuolar protein sorting 28 (Vps28), a component of the ESCRT-I (endosomal complex required for transport I), plays an important role in pathogen life cycle. Here, we investigated reciprocal regulation between Vps28 and foot-and-mouth disease virus (FMDV). Overexpression decreased FMDV replication. On contrary, knockdown increased viral Subsequently, mechanistic study showed that destabilized replication (RC) by associating with 3A rather than 2C protein. In addition, targeted VP0, VP1, VP3 degradation to inhibit To counteract this, utilized tactics restrict promote degraded mainly through ubiquitin-proteasome pathway. Additional data demonstrated 2B proteins recruited E3 ubiquitin ligase tripartite motif-containing 21 degrade at Lys58 Lys25, respectively, 3Cpro autophagy its protease activity. Meantime, 3Cpro-mediated principally alleviated ability propagation. Intriguingly, also N-terminal C-terminal domains were responsible suppression replication, which suggested elaborated counteraction Vps28. Collectively, our results first investigate ESCRTs host defense against picornavirus unveil underlying strategies evade machinery triumphant IMPORTANCE ESCRT positive roles entry, budding. However, little has been reported on negative effects during infection. uncovered novel subunit The indicated RC impaired structural hijacked intracellular pathways downregulate expression thus promoted Our findings provide insights into how regulates cycles elucidate additional information regarding antiviral

Язык: Английский

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SAMHD1 enhances HIV-1-induced apoptosis in monocytic cells via the mitochondrial pathway

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

SUMMARY Sterile alpha motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) inhibits HIV-1 replication in non-dividing cells by reducing the intracellular dNTP pool. SAMHD1 enhances spontaneous apoptosis cells, but its effects on HIV-1-induced underlying mechanisms remain unknown. Here we uncover a new mechanism which monocytic through mitochondrial pathway. We found that endogenous levels induced infection dividing THP-1 cells. Mechanistically, expression decreases membrane potential promotes cytochrome c release thereby enhancing apoptotic SAMHD1-enhanced is associated with increased of pro-apoptotic BCL-2-interacting killer (BIK) further demonstrated BIK contributes to during infection. Overall, our results reveal an unappreciated regulatory via pathway

Язык: Английский

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Regulation of viral replication by host restriction factors

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 23, 2025

Viral infectious diseases, caused by numerous viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), enterovirus (EV), human immunodeficiency (HIV), hepatitis B (HBV), and papillomavirus (HPV), pose a continuous threat to global health. As obligate parasites, rely on host cells replicate, have developed defense mechanisms counteract viral infection. Host restriction factors (HRFs) are critical components of the early antiviral response. These cellular proteins inhibit replication spread impeding essential steps in life cycle, such as entry, genome transcription replication, protein translation, particle assembly, release. This review summarizes current understanding how with primary focus their diverse against range viruses, SARS-CoV-2, virus, enteroviruses, papillomavirus. In addition, we highlight crucial role these shaping host-virus interactions discuss potential targets for drug development.

Язык: Английский

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TRIM21-mediated PRMT1 degradation attenuates colorectal cancer malignant progression

Cell Death and Disease, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 31, 2025

Язык: Английский

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