Regulation of viral replication by host restriction factors

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 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.

Language: Английский

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Ubiquitin-dependent proteasomal degradation of small hepatitis B virus surface antigen mediated by TRIM21 and antagonized by OTUD4

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

Published: April 25, 2025

ABSTRACT The small hepatitis B surface antigen (SHBs) is the most abundant virus (HBV) protein in individuals infected with HBV, and clearance of HBV antigen, which primarily composed SHBs, considered a surrogate biomarker for achieving functional cure chronic HBV. Understanding SHBs degradation crucial its elimination targeted eradication strategies. This study demonstrates that undergoes via ubiquitin/proteasome pathway, through K48-linked ubiquitination, K122 as critical ubiquitination site. Utilizing immunoprecipitation mass spectrometry, we identified TRIM21 (an E3 ubiquitin ligase) OTUD4 (a deubiquitinase) key regulators SHBs. We verified direct interaction between TRIM21’s coiled-coil domain, well N-terminal amino acids 1–180 OTUD4, using coimmunoprecipitation glutathione S-transferase (GST) pull-down assays both vivo vitro settings. was observed to reduce stability abundance by promoting polyubiquitination, whereas acted negate effects TRIM21-induced thereby stabilizing increasing levels Notably, TRIM21-mediated substantially impaired subviral particle virion production biological activities such migratory angiogenic capabilities, opposite effect produced introduction OTUD4. These findings suggest modulate function ubiquitination-dependent proteasomal offering new insights into clearing intervening progression HBV-related liver diseases. IMPORTANCE structural component particles infection. Gaining better understanding pathways may help inform strategies potentially support design therapies. However, specific mechanisms processes involved remain largely unexplored. reveals degraded specifically at promotes enhancing while stabilizes counteracting effects. reduces stability, production, related activities, accumulation. highlight roles regulating function, potential interventions

Language: Английский

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dNTP depletion and beyond: the multifaceted nature of SAMHD1-mediated viral restriction

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

Published: April 25, 2025

ABSTRACT SAMHD1 is a dNTPase of mammalian cells. In 2011, was found to be host restriction factor against retroviruses through dNTP reduction. Recent research provides evidence that the antiviral mechanisms cannot explained solely by its activity. Instead, versatility SAMHD1-mediated various viruses suggests extend beyond depletion. This explains multifaceted and broad functions play significant role in innate immunity.

Language: Английский

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SAMHD1 Impairs HIV-1 Gene Expression and Negatively Modulates Reactivation of Viral Latency in CD4 ⁺ T Cells

Journal of Virology, Journal Year: 2018, Volume and Issue: 92(15)

Published: May 23, 2018

A critical barrier to developing a cure for HIV-1 infection is the long-lived viral reservoir that exists in resting CD4 + T cells, main targets of HIV-1. The maintained through variety mechanisms, including regulation LTR promoter. host protein SAMHD1 restricts replication nondividing but its role latency remains unknown. Here we report new function regulating latency. We found suppressed promoter-driven gene expression and reactivation cell lines primary cells. Furthermore, bound vitro latently infected T-cell line, suggesting binding may negatively modulate Our findings indicate novel latency, which enhances our understanding mechanisms proviral

Language: Английский

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TRIM21 inhibits porcine epidemic diarrhea virus proliferation by proteasomal degradation of the nucleocapsid protein

Archives of Virology, Journal Year: 2021, Volume and Issue: 166(7), P. 1903 - 1911

Published: April 26, 2021

Language: Английский

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