MARCH8 Restricts Influenza A Virus Infectivity but Does Not Downregulate Viral Glycoprotein Expression at the Surface of Infected Cells

mBio, Journal Year: 2021, Volume and Issue: 12(5)

Published: Sept. 14, 2021

Membrane-associated RING-CH8 (MARCH8) impairs the cell surface expression of envelope glycoproteins from different viruses, reducing their incorporation into virions. Using stable lines with inducible MARCH8 expression, we show that did not alter susceptibility to influenza A virus (IAV) infection, but virions released infected cells were markedly less infectious. Knockdown endogenous confirmed its effect on IAV infectivity. The impaired infectivity both H3N2 and H1N1 strains was dependent E3 ligase activity. Although in presence expressed smaller amounts viral hemagglutinin (HA) neuraminidase (NA) proteins, there no impact levels HA, NA, or matrix 2 (M2) proteins detected cells. Moreover, mutation lysine residues cytoplasmic tails and/or M2, M1 protein, abrogate MARCH8-mediated restriction. While MARCH1 -8 target similar immunological ligands restrict HIV-1, only inhibited Deletion N-terminal (N-CT) domain it be a critical determinant inhibition. Of interest, deletion N-CT replacement resulted acquisition Together, these data demonstrate restricts late stage replication by mechanism distinct reported activity against other viruses. is essential for anti-IAV activity, whereas inhibits ability IAV. IMPORTANCE antiviral has been associated downregulation range resulting reduced nascent Here, at replication, this cells, pointing Our studies also differential infectivity, highlighting role each protein modulating Overall, provide novel insights regarding mechanisms which MARCH contribute cell-intrinsic immunity

Language: Английский

---

MARCH8 inhibits pseudorabies virus replication by trapping the viral cell-to-cell fusion complex in the trans-Golgi network

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 274, P. 133463 - 133463

Published: Aug. 1, 2024

Language: Английский

---

MARCH8: the tie that binds to viruses

FEBS Journal, Journal Year: 2021, Volume and Issue: 289(13), P. 3642 - 3654

Published: May 16, 2021

Membrane-associated RING-CH (MARCH) family member proteins are RING-finger E3 ubiquitin ligases that known to downregulate cellular transmembrane proteins. MARCH8 is a novel antiviral factor inhibits HIV-1 envelope glycoprotein and vesicular stomatitis virus G by downregulating these glycoproteins from the cell surface, resulting in their reduced incorporation into virions. More recently, we have found reduces viral infectivity via two different mechanisms. Additionally, several groups reported further or virus-supportive functions of protein its other In this review, summarize current knowledge about molecular mechanisms which can regulate homeostasis inhibit occasionally support enveloped infection.

Language: Английский

---

Role of E3 ubiquitin ligases and deubiquitinating enzymes in SARS-CoV-2 infection

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: June 9, 2023

Ever since its emergence in 2019, COVID-19 has rapidly disseminated worldwide, engendering a pervasive pandemic that profoundly impacted healthcare systems and the socio-economic milieu. A plethora of studies been conducted targeting pathogenic virus, SARS-CoV-2, to find ways combat COVID-19. The ubiquitin-proteasome system (UPS) is widely recognized as crucial mechanism regulates human biological activities by maintaining protein homeostasis. Within UPS, ubiquitination deubiquitination, two reversible modifications, substrate proteins have extensively studied implicated pathogenesis SARS-CoV-2. regulation E3 ubiquitin ligases DUBs(Deubiquitinating enzymes), which are key enzymes involved modification processes, determines fate proteins. Proteins associated with SARS-CoV-2 may be retained, degraded, or even activated, thus affecting ultimate outcome confrontation between host. In other words, clash host can viewed battle for dominance over DUBs, from standpoint regulation. This review primarily aims clarify mechanisms virus utilizes along own viral similar enzyme activities, facilitate invasion, replication, escape, inflammation. We believe gaining better understanding role DUBs offer novel valuable insights developing antiviral therapies.

Language: Английский

---

Furin Egress from the TGN is Regulated by Membrane‐Associated RING‐CH Finger (MARCHF) Proteins and Ubiquitin‐Specific Protease 32 (USP32) via Nondegradable K33‐Polyubiquitination

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 19, 2024

Abstract Furin primarily localizes to the trans ‐Golgi network (TGN), where it cleaves and activates a broad range of immature proproteins that play critical roles in cellular homeostasis, disease progression, infection. is retrieved from endosomes TGN after being phosphorylated, but still unclear how furin exits initiate post‐Golgi trafficking its activity regulated TGN. Here three membrane‐associated RING‐CH finger (MARCHF) proteins (2, 8, 9) are identified as E3 ubiquitin ligases, which catalyze K33‐polyubiquitination. Polyubiquitination prevents maturation by blocking ectodomain cleavage inside cells promotes egress shedding. Further ubiquitin‐specific protease 32 (USP32) deubiquitinase counteracts MARCHF inhibitory on furin. Thus, an interplay between polyubiquitination phosphorylation. required for anterograde transport inhibits proprotein convertase activity, phosphorylation retrograde produce fully active cells.

Language: Английский

---