MARCH8 Restricts RSV Replication by Promoting Cellular Apoptosis Through Ubiquitin-Mediated Proteolysis of Viral SH Protein

Viruses, Journal Year: 2024, Volume and Issue: 16(12), P. 1935 - 1935

Published: Dec. 18, 2024

Numerous host factors function as intrinsic antiviral effectors to attenuate viral replication. MARCH8 is an E3 ubiquitin ligase that has been identified a restriction factor inhibits the replication of various viruses. This study elucidated mechanism by which restricts respiratory syncytial virus (RSV) through selective degradation small hydrophobic (SH) protein. We demonstrated directly interacts with RSV-SH and catalyzes its ubiquitination at lysine 13, leading SH via ubiquitin-lysosomal pathway. Functionally, expression enhances RSV-induced apoptosis degradation, ultimately reducing titers. Conversely, RSV strain harboring SH-K13R mutation exhibited prolonged protein stability attenuated in infected cells, even presence MARCH8. Targeted depletion cellular survival potentially increases persistence. These findings demonstrate promotes early elimination virus-infected cells abrogating anti-apoptotic SH, thereby transmission. Our provides novel insights into interplay between evasion strategies, providing new therapeutic approaches for infections.

Language: Английский

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Determining the antiviral mechanism of MARCH2

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 19, 2023

Abstract Membrane-associated RING-CH (MARCH) 2 protein is a member of the MARCH family finger E3 ubiquitin ligases that have important functions in regulating levels proteins found on cell surface. MARCH1, and 8 inhibit HIV-1 infection by preventing incorporation envelope glycoproteins nascent virions. However, better understanding mechanism utilized to restrict needed. In this report, we identify an amino acid human MARCH2, absent mouse critical for its antiretroviral function. Moreover, map domains MARCH2 restricting as well binding glycoproteins. Our findings reveal new aspects antiviral potential implications all with functions.

Language: Английский

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A Glu-Glu-Tyr Sequence in the Cytoplasmic Tail of the M2 Protein Renders Influenza A Virus Susceptible to Restriction of the Hemagglutinin-M2 Association in Primary Human Macrophages

Journal of Virology, Journal Year: 2022, Volume and Issue: 96(18)

Published: Sept. 13, 2022

Influenza A virus (IAV) assembly at the plasma membrane is orchestrated by least five viral components, including hemagglutinin (HA), neuraminidase (NA), matrix (M1), ion channel M2, and ribonucleoprotein (vRNP) complexes, although particle formation observed with expression of only HA and/or NA. While these components are expressed efficiently in primary human monocyte-derived macrophages (MDMs) upon IAV infection, this cell type does not support efficient HA-M2 association membrane. Both defects specific to MDMs can be reversed disruption F-actin. However, relationship between two unclear. Here, we examined whether M2 contributes if so, which region determines susceptibility MDM-specific actin-dependent suppression. An analysis using correlative fluorescence scanning electron microscopy showed that an M2-deficient failed form budding structures surface even after F-actin was disrupted, indicating essential for MDM surface. Notably, proximity ligation revealed a single amino acid substitution Glu-Glu-Tyr sequence (residues 74 76) cytoplasmic tail allowed occur intact actin cytoskeleton. This phenotype did correlate known phenotypes mutants regarding M1 interaction or vRNP packaging epithelial cells. Overall, our study identified as target restriction assembly, requires tail. IMPORTANCE Human represent nonpermissive influenza (IAV). We previously close proteins blocked MDMs. express factor against they lack dependency promoting remained unknown. In current study, determined protein necessary but also molecular suppression assembly. Substitutions alleviated block both production These findings suggest factors factor(s) inhibits formation. High conservation rendering highlights potential antiviral strategies.

Language: Английский

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The membrane-associated ubiquitin ligase MARCHF8 stabilizes the human papillomavirus oncoprotein E7 by degrading CUL1 and UBE2L3 in head and neck cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 4, 2023

The human papillomavirus (HPV) oncoprotein E7 is a relatively short-lived protein required for HPV-driven cancer development and maintenance. degraded through ubiquitination mediated by cullin 1 (CUL1) the ubiquitin-conjugating enzyme E2 L3 (UBE2L3). However, proteins are maintained at high levels in most HPV-positive cells. A previous proteomics study has shown that UBE2L3 CUL1 increased knockdown of E3 ubiquitin ligase membrane-associated ring-CH-type finger 8 (MARCHF8). We have recently demonstrated HPV upregulates MARCHF8 expression keratinocytes head neck (HPV+ HNC) Here, we report stabilizes degrading components SKP1-CUL1-F-box (SCF) complex HPV+ HNC found

Language: Английский

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