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Mutant cellular AP-1 proteins promote expression of a subset of Epstein-Barr virus late genes in the absence of lytic viral DNA replication
Danielle E. Lyons, Kuan-Ping Yu, Jason A. Vander Heiden, Lee Heston, Dirk P. Dittmer, Ayman El-Guindy, George Miller
Published: 18 July 2018 by American Society for Microbiology in Journal of Virology
American Society for Microbiology, 10.1128/jvi.01062-18
Epstein-Barr virus (EBV) ZEBRA protein activates the EBV lytic cycle. Cellular AP-1 proteins with alanine-to-serine substitutions homologous to ZEBRA(S186) assume some functions of EBV ZEBRA. These AP-1(A/S) mutants bind methylated EBV DNA and activate expression of some EBV genes. Here we compare expression of 67 viral genes induced by ZEBRA versus induced AP-1(A/S) proteins. AP-1(A/S) activated 24 genes to high levels and 15 genes to intermediate levels; activation of 28 genes by AP-1(A/S) was severely impaired. We show that AP-1(A/S) proteins are defective at stimulating viral lytic DNA replication. The impairment of expression of many late genes, when compared to ZEBRA, is likely due to the inability of AP-1(A/S) proteins to promote viral DNA replication. However, even in the absence of detectable viral DNA replication, AP-1(A/S) proteins stimulated expression of a subgroup of late genes that encode viral structural proteins and immune-modulators. In response to ZEBRA, expression of this subgroup of late genes was inhibited by phosphonoacetic acid (PAA), which is a potent viral replication inhibitor. However, when the lytic cycle was activated by AP-1(A/S), PAA did not reduce expression of this subgroup of late genes. We also provide genetic evidence, using the BMRF1 knockout bacmid, that these genes are true late genes in response to ZEBRA. AP-1(A/S) binds to the promoter region of at least one of these late genes, BDLF3, encoding an immune-modulator. IMPORTANCE Mutant c-Jun and c-Fos proteins selectively activate expression of EBV lytic genes, including a subgroup of viral late genes, in the absence of viral DNA replication. These findings indicate that newly synthesized viral DNA is not invariably required for viral late gene expression. While viral DNA replication may be obligatory for late gene expression driven by viral transcription factors, it does not limit the ability of cellular transcription factors to activate expression of some viral late genes. Our results show that expression of all late genes may not be strictly dependent on viral lytic DNA replication. The c-Fos A151S mutation has been identified in a human cancer. c-Fos A151S in combination with wild-type c-Jun activates the EBV lytic cycle. Our data provides proof of principle that mutant cellular transcription factors could cause aberrant regulation of viral lytic cycle gene expression and play important roles in EBV-associated diseases.
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Epilogue: Collecting Fragments—Towards (Post-)Yugoslav Activist Archives
Bojan Bilić
Published: 18 July 2018 by Springer-Verlag in Lesbian Activism in the (Post-)Yugoslav Space
Springer-Verlag, 10.1007/978-3-319-77754-2_9
This chapter takes a look at the four volumes on the politics of activism in the (post-)Yugoslav space that we, as an affective-epistemic community of more than 50 authors, have published over the last six years. Our volumes have documented and analysed activist initiatives that have tried to take issue with powerful nationalist paradigms based on exclusion and discrimination. Our texts represent archives of both documentary material, including personal testimonies, documents, leaflets, activist publications, as well as emotional states, such as fears, disappointments, hopes, and joys that accompany activism. These archives are not only a resource for responding to a traumatic experience that we, as post-Yugoslavs, share, but they can also offer new perspectives for activist endeavours in a post-conflict/post-socialist environment.
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Nucleotide-Driven Triple-State Remodeling of the AAA-ATPase Channel in the Activated Human 26S Proteasome
Y. Zhu, W.L. Wang, D. Yu, Q. Ouyang, Y. Lu, Y. Mao
Published: 18 July 2018 by Protein Data Bank
Protein Data Bank, 10.2210/pdb5vfs/pdbx
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Ternary complex crystal structure of DNA polymerase Beta with a dideoxy terminated primer with dATP
V.K. Batra, S.H. Wilson
Published: 18 July 2018 by Protein Data Bank
Protein Data Bank, 10.2210/pdb6cr4/pdb
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Structure of Salmonella Effector SseK3 E258Q mutant
I.Y.W. Chung, M. Cygler
Published: 18 July 2018 by Protein Data Bank
Protein Data Bank, 10.2210/pdb6dus/pdb
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Structure of the HAD domain of effector protein Lem4 (lpg1101) from Legionella pneumophila
K.A. Beyrakhova, C. Xu, M. Cygler
Published: 18 July 2018 by Protein Data Bank
Protein Data Bank, 10.2210/pdb6cgj/pdb
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But What Is Accountability?
Russ Glennon, Laurence Ferry, Peter Murphy, Kirsten Greenhalgh
Published: 18 July 2018 by Springer-Verlag in Public Service Accountability
Springer-Verlag, 10.1007/978-3-319-93384-9_1
The genesis of this book originally derives from a report for the National Audit Office. This examined the government’s ability to demonstrate the quality of service delivery in locally delivered public services in England, a responsibility, previously overseen by the former Audit Commission, between the 2010 and 2015 general elections. The Audit Commission formally closed on 31st March 2015 and part of its role transferred to the NAO. The report to the NAO provided a ‘state of play’ evaluation for the four areas of Local Government, Health and Social Care, the Police, and Fire and Rescue Services. It identified, adapted, and tested some of the dominant concepts of financial, service, and organisational accountability that had been applied and used in the contemporary UK context.
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PanDDA analysis group deposition of models with modelled events (e.g. bound ligands) -- Crystal Structure of HAO1 in complex with FMOPL000388a
S. MacKinnon, G.A. Bezerra, T. Krojer, A.R. Bradley, R. Talon, J. Brandao-Neto, A. Douangamath, F. Von Delft, C.H. Arrowsmith, A. Edwards, C. Bountra, U. Oppermann, P.E. Brennan, W.W. Yue
Published: 18 July 2018 by Protein Data Bank
Protein Data Bank, 10.2210/pdb5qib/pdb
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Cryo-EM structure of human TRPV6-Y467A in complex with 2-Aminoethoxydiphenyl borate (2-APB)
A.K. Singh, K. Saotome, L.L. McGoldrick, A.I. Sobolevsky
Published: 18 July 2018 by Protein Data Bank
Protein Data Bank, 10.2210/pdb6d7t/pdb
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Crystal structure of human GDP-D-mannose 4,6-dehydratase in complex with GDP-4k6d-Man
M. Pfeiffer, T. Krojer, C. Johansson, F. Von Delft, C. Bountra, C.H. Arrowsmith, A. Edwards, B. Nidetzky, U. Oppermann, Structural Genomics Consortium
Published: 18 July 2018 by Protein Data Bank
Protein Data Bank, 10.2210/pdb6gpl/pdb
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