Initial Characterization of the Epstein–Barr Virus BSRF1 Gene Product

Yanagi, Yusuke; Masud, H. M. Abdullah Al; Watanabe, Takahiro; Sato, Yoshitaka; Goshima, Fumi; Kimura, Hiroshi; Murata, Takayuki

doi:10.3390/v11030285

Cited by 19 publications

(37 citation statements)

References 27 publications

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“…2b). These results are consistent with the previously reported association between HSV-1 pUL7 and pUL51 12 , and a recent study of BSRF1 interaction partners in HEK293T cells with an incorporated EBV genome 14 . Therefore, these two tegument proteins clearly form a functional complex in a conserved manner across Herpesviridae and we focused on studying the structure of the BBRF2-BSRF1 complex to understand the molecular basis of their association.…”

Section: Resultssupporting

confidence: 93%

“…BBRF2 is an EBV tegument protein that has putative homologues in all three herpesvirus subfamilies 10 . BBRF2 was recently shown to be a binding partner of BSRF1, another poorly characterized EBV tegument protein 14 . Complexing of the two proteins alters the subcellular localization of BBRF2, and prevents BSRF1 from degradation, which ultimately augments viral infectivity 15 .…”

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confidence: 99%

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Structure of Epstein-Barr virus tegument protein complex BBRF2-BSRF1 reveals its potential role in viral envelopment

Luo

Cao

et al. 2020

Nat Commun

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Epstein-Barr virus (EBV) is a γ-herpesvirus associated with the occurrence of several human malignancies. BBRF2 and BSRF1 are two EBV tegument proteins that have been suggested to form a hetero-complex and mediate viral envelopment, but the molecular basis of their interaction and the functional mechanism of this complex remains unknown. Here, we present crystal structures of BBRF2 alone and in complex with BSRF1. BBRF2 has a compact globular architecture featuring a central β-sheet that is surrounded by 10 helices, it represents a novel fold distinct from other known protein structures. The central portion of BSRF1 folds into two tightly associated antiparallel α-helices, forming a composite four-helix bundle with two α-helices from BBRF2 via a massive hydrophobic network. In vitro, a BSRF1-derived peptide binds to BBRF2 and reduces the number of viral genome copies in EBV-positive cells. Exogenous BBRF2 and BSRF1 co-localize at the Golgi apparatus. Furthermore, BBRF2 binds capsid and capsid-associated proteins, whereas BSRF1 associates with glycoproteins. These findings indicate that the BBRF2-BSRF1 complex tethers EBV nucleocapsids to the glycoprotein-enriched Golgi membrane, facilitating secondary envelopment.

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Section: Resultssupporting

confidence: 93%

mentioning

confidence: 99%

Structure of Epstein-Barr virus tegument protein complex BBRF2-BSRF1 reveals its potential role in viral envelopment

Luo

Cao

et al. 2020

Nat Commun

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“…Last but not least, modulation of autophagy by BALF0 and BALF1 may directly or indirectly contribute to virion morphogenesis. Although initial work by Johannsen and colleagues did not identify BALF0 and BALF1 in purified EBV virions [67], another study led to co-purification of BALF0 and BALF1 with BSRF1 [68], an EBV tegument protein that is homologous to HSV-1 unique long 51 (UL51) and HCMV UL71, which is involved in virion egress. This result, which shed new light on the putative function of BALF0 and BALF1 during the EBV lytic cycle, is strongly reminiscent of a recent report indicating that vBcl-2 from KSHV could similarly interact with tegument protein ORF55 [69].…”

Section: Discussionmentioning

confidence: 99%

Epstein–Barr Virus BALF0 and BALF1 Modulate Autophagy

Shao

Borde

Quignon

et al. 2019

Viruses

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Autophagy is an essential catabolic process that degrades cytoplasmic components within the lysosome, therefore ensuring cell survival and homeostasis. A growing number of viruses, including members of the Herpesviridae family, have been shown to manipulate autophagy to facilitate their persistence or optimize their replication. Previous works showed that the Epstein–Barr virus (EBV), a human transforming gammaherpesvirus, hijacked autophagy during the lytic phase of its cycle, possibly to favor the formation of viral particles. However, the viral proteins that are responsible for an EBV-mediated subversion of the autophagy pathways remain to be characterized. Here we provide the first evidence that the BALF0/1 open reading frame encodes for two conserved proteins of the Bcl-2 family, BALF0 and BALF1, that are expressed during the early phase of the lytic cycle and can modulate autophagy. A putative LC3-interacting region (LIR) has been identified that is required both for BALF1 colocalization with autophagosomes and for its ability to stimulate autophagy.

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“…Both the pUL7 and pUL51 homologues from murine γ-herpesvirus 68 are essential for virus replication (22). The putative pUL51 homologue BSRF1 from Epstein-Barr virus associates with Golgi membranes and siRNA knock-down of BSRF1 in B95-8 cells prevents virion production (23). The KSHV homologue of pUL7, pORF42, is similarly required for efficient virion production (24).…”

Section: Main Text Introductionmentioning

confidence: 99%

“…The KSHV homologue of pUL7, pORF42, is similarly required for efficient virion production (24). While a direct interaction has not been shown for the pUL7 and pUL51 homologues from β-or γ-herpesviruses, the EBV homologues BBRF2 and BSRF1 have been shown to co-precipitate from transfected cells (23).…”

Section: Main Text Introductionmentioning

confidence: 99%

Structure of herpes simplex virus pUL7:pUL51, a conserved complex required for efficient herpesvirus assembly

Butt

Owen

Jeffries³

et al. 2019

Preprint

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Herpesviruses are an ancient family of highly-prevalent human and animal pathogens that acquire their membrane envelopes in the cytoplasm of infected cells. While multiple conserved viral proteins are known to be required for efficient herpesvirus production, many of these proteins lack identifiable structural homologues and the molecular details of herpesvirus assembly remain unclear. We have characterized the complex of assembly proteins pUL7 and pUL51 from herpes simplex virus (HSV)-1, an α-herpesvirus, using multi-angle light scattering and small-angle X-ray scattering with chemical crosslinking. HSV-1 pUL7 and pUL51 form a stable 1:2 complex that is capable of higher-order oligomerization in solution. We solved the crystal structure of this complex, revealing a core heterodimer comprising pUL7 bound to residues 41-125 of pUL51. While pUL7 adopts a previously-unseen compact fold, the extended helix-turn-helix conformation of pUL51 resembles the cellular endosomal complex required for transport (ESCRT)-III component CHMP4B, suggesting a direct role for pUL51 in promoting membrane scission during virus assembly. We demonstrate that the interaction between pUL7 and pUL51 homologues is conserved across human α-, β-and γ-herpesviruses, as is their association with trans-Golgi membranes in cultured cells. However, pUL7 and pUL51 homologues do not form complexes with their respective partners from different virus families, suggesting that the molecular details of the interaction interface have diverged. Our results demonstrate that the pUL7:pUL51 complex is conserved across the herpesviruses and provide a structural framework for understanding its role in herpesvirus assembly. Significance StatementHerpesviruses are extremely common human pathogens that cause diseases ranging from cold sores to cancer. Herpesvirus acquire their membrane envelope in the cytoplasm via a conserved pathway, the molecular details of which remain unclear. We have solved the structure of a complex between herpes simplex virus (HSV)-1 proteins pUL7 and pUL51, two proteins that are required for efficient HSV-1 assembly. We show that formation of this complex is conserved across distantly-related human herpesviruses, as is the association of these homologues with cellular membranes that are used for virion assembly. While pUL7 adopts a previously-unseen fold, pUL51 resembles key cellular membrane-remodeling complex components, suggesting that the pUL7:pUL51 complex may play a direct role in deforming membranes to promote virion assembly.

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Initial Characterization of the Epstein–Barr Virus BSRF1 Gene Product

Cited by 19 publications

References 27 publications

Structure of Epstein-Barr virus tegument protein complex BBRF2-BSRF1 reveals its potential role in viral envelopment

Structure of Epstein-Barr virus tegument protein complex BBRF2-BSRF1 reveals its potential role in viral envelopment

Epstein–Barr Virus BALF0 and BALF1 Modulate Autophagy

Structure of herpes simplex virus pUL7:pUL51, a conserved complex required for efficient herpesvirus assembly

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