Rta is an Epstein-Barr virus tegument protein that improves the stability of capsid protein BORF1

Huang, Hsiang-Hung; Wang, Wen‐Hung; Feng, Tzu-Hui; Chang, Li-Kwan

doi:10.1016/j.bbrc.2020.01.017

Cited by 4 publications

(7 citation statements)

References 32 publications

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“…Our earlier study showed that EBV Rta interacts with TRIM5α [ 26 ]. As Rta is closely associated with the EBV capsid and present in the tegument layer [ 31 ], this study, therefore, investigated whether TRIM5α could similarly interact with EBV capsid proteins. As BORF1 plays a pivotal role in bringing EBV capsid proteins into the nucleus for capsid assembly [ 29 ], this study investigated whether TRIM5α interacted with BORF1.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, our earlier study revealed that TRIM5α is mainly localized in the cytosol during latency but colocalizes with Rta in the nucleus after lytic activation [ 26 ]. Rta is a tegument protein that colocalizes with BORF1 in the nucleus during lytic induction [ 31 ], suggesting that TRIM5α is involved in nucleocapsid assembly. Whether TRIM5α recognizes EBV capsids during lytic activation will be further elucidated.…”

Section: Discussionmentioning

confidence: 99%

“…Protein samples were mixed with sample buffer (62.5 mM Tris-HCl pH 6.8, 2% sodium dodecyl sulfate (SDS), 5% β-mercaptoethanol, 10% glycerol, 2 mM ethylenediaminetetraacetic acid (EDTA), 0.005% bromophenol blue). After heating at 95 °C for 5 min, proteins were then separated by 10–12% SDS-polyacrylamide gel electrophoresis (SDS-PAGE) gel at 168V and electro-transferred to nitrocellulose (NC) membrane (Merck Millipore, Burlington, MA, USA) in transfer buffer (25 mM Tris-HCl, 5.5% glycine, 20% methanol) at 94V, 400 mA, for 1 h. After blocking with 5% defatted milk (Anchor, Auckland, New Zealand) in TBST buffer (50 mM Tris-HCl pH 7.5, 150 mM NaCl, 0.05% Tween 20) for 20 min, membranes were then probed by anti-TRIM5α (Santa Cruz, Dallas, TX, USA), anti-Flag (Sigma, St. Louis, MO, USA), anti-BORF1 [ 31 ], anti-HA (Roche, Basel, Switzerland, Cell Signaling, Danvers, MA, USA), anti-GFP (Santa Cruz, Dallas, TX, USA), anti-His (Sigma), anti-GST (Santa Cruz, Dallas, TX, USA), anti-LC3B (GeneTex, Irvine, CA, USA), anti-Ub (Santa Cruz, Dallas, TX, USA), and anti-α-tubulin (Sigma, St. Louis, MO, USA) antibodies.…”

Section: Methodsmentioning

confidence: 99%

“…Of these capsid proteins, BORF1 has a nuclear localization signal (NLS) to facilitate nuclear transport [ 29 ]; the nuclear import of BDLF1 and VCA relies on their interaction with BORF1 [ 30 ]. A recent study showed that Rta is an EBV tegument protein that binds to the capsid [ 31 ]. Therefore, in this study, we wished to elucidate if TRIM5α could interact with EBV capsid proteins, possibly via the interaction with Rta, and examine how such interaction would affect EBV replication.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α

Huang

et al. 2022

IJMS

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TRIM5α is a host anti-retroviral restriction factor that destroys human immunodeficiency virus (HIV) virions and triggers innate immune signaling. TRIM5α also mediates the autophagic degradation of target proteins via TRIMosome formation. We previously showed that TRIM5α promotes Epstein-Barr virus (EBV) Rta ubiquitination and attenuates EBV lytic progression. In this study, we sought to elucidate whether TRIM5α can interact with and induce the degradation of EBV capsid proteins. Glutathione S-transferase (GST) pulldown and immunoprecipitation assays were conducted to identify interacting proteins, and mutants were generated to investigate key binding domains and ubiquitination sites. Results showed that TRIM5α binds directly with BORF1, an EBV capsid protein with a nuclear localization signal (NLS) that enables the transport of EBV capsid proteins into the host nucleus to facilitate capsid assembly. TRIM5α promotes BORF1 ubiquitination, which requires the surface patch region in the TRIM5α PRY/SPRY domain. TRIM5α expression also decreases the stability of BORF1(6KR), a mutant with all lysine residues mutated to arginine. However, chloroquine treatment restores the stability of BORF1(6KR), suggesting that TRIM5α destabilizes BORF1 via direct recognition of its substrate for autophagic degradation. These results reveal novel insights into the antiviral impact of TRIM5α beyond retroviruses.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α

Huang

et al. 2022

IJMS

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“…Endogenous BRRF2 protein was detectable by western blotting of EBV virion using our antibody [ 14 ], and its KSHV homolog ORF48 protein is also identified by mass spectrometry in the virion fraction [ 18 ]. BRLF1 protein is recently identified in EBV virion fraction by western blotting [ 19 ], and the KSHV homolog ORF50 is detected by western blotting of KSHV virion proteins [ 11 ].…”

Section: Composition Of Ebv Tegument Proteinsmentioning

confidence: 99%

Tegument proteins of Epstein-Barr virus: Diverse functions, complex networks, and oncogenesis

Murata

2023

Tumour Virus Research

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Transcriptional regulators of human oncoviruses: structural and functional implications for anticancer therapy

et al. 2022

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Transcription is often the first biosynthetic event of viral infection. Viruses produce preferentially viral transcriptional regulators (vTRs) essential for expressing viral genes and regulating essential host cell proteins to enable viral genome replication. As vTRs are unique viral proteins that promote the transcription of viral nucleic acid, vTRs interact with host proteins to suppress detection and immune reactions to viral infection. Thus, vTRs are promising therapeutic targets that are sequentially and structurally distinct from host cell proteins. Here, we review vTRs of three human oncoviruses: HBx of hepatitis B virus, HBZ of human T-lymphotropic virus type 1, and Rta of Epstein–Barr virus. We present three cunningly exciting and dangerous transcription strategies that make viral infections so efficient. We use available structural and functional knowledge to critically examine the potential of vTRs as new antiviral-anticancer therapy targets. For each oncovirus, we describe (i) the strategy of viral genome transcription; (ii) vTRs’ structure and binding partners essential for transcription regulation; and (iii) advantages and challenges of vTR targeting in antiviral therapies. We discuss the implications of vTR regulation for oncogenesis and perspectives on developing novel antiviral and anticancer strategies.

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Rta is an Epstein-Barr virus tegument protein that improves the stability of capsid protein BORF1

Cited by 4 publications

References 32 publications

Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α

Regulation of Epstein-Barr Virus Minor Capsid Protein BORF1 by TRIM5α

Tegument proteins of Epstein-Barr virus: Diverse functions, complex networks, and oncogenesis

Transcriptional regulators of human oncoviruses: structural and functional implications for anticancer therapy

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