scholarly journals Molecular mechanism underlying selective inhibition of mRNA nuclear export by herpesvirus protein ORF10

2020 ◽  
Vol 117 (43) ◽  
pp. 26719-26727
Author(s):  
Han Feng ◽  
Huabin Tian ◽  
Yong Wang ◽  
Qixiang Zhang ◽  
Ni Lin ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Nuclear Export ◽  
Rna Binding ◽  
Mrna Export ◽  
Direct Interaction ◽  
Selective Inhibition ◽  
Murine Gammaherpesvirus ◽  
Binding Groove ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

Viruses employ multiple strategies to inhibit host mRNA nuclear export. Distinct to the generally nonselective inhibition mechanisms, ORF10 from gammaherpesviruses inhibits mRNA export in a transcript-selective manner by interacting with Rae1 (RNA export 1) and Nup98 (nucleoporin 98). We now report the structure of ORF10 from MHV-68 (murine gammaherpesvirus 68) bound to the Rae1–Nup98 heterodimer, thereby revealing detailed intermolecular interactions. Structural and functional assays highlight that two highly conserved residues of ORF10, L60 and M413, play critical roles in both complex assembly and mRNA export inhibition. Interestingly, although ORF10 occupies the RNA-binding groove of Rae1–Nup98, the ORF10–Rae1–Nup98 ternary complex still maintains a comparable RNA-binding ability due to the ORF10–RNA direct interaction. Moreover, mutations on the RNA-binding surface of ORF10 disrupt its function of mRNA export inhibition. Our work demonstrates the molecular mechanism of ORF10-mediated selective inhibition and provides insights into the functions of Rae1–Nup98 in regulating host mRNA export.

scholarly journals Mex67p of Schizosaccharomyces pombeInteracts with Rae1p in Mediating mRNA Export

2000 ◽  
Vol 20 (23) ◽  
pp. 8767-8782 ◽  
Author(s):  
Jin Ho Yoon ◽  
Dona C. Love ◽  
Anjan Guhathakurta ◽  
John A. Hanover ◽  
Ravi Dhar
Keyword(s):  
Nuclear Export ◽  
Rna Binding ◽  
Fluorescent Protein ◽  
Synthetic Lethality ◽  
Sequence Similarity ◽  
Mrna Export ◽  
Nuclear Periphery ◽  
Nuclear Pore ◽  
Multicopy Suppressor ◽  
Accessory Factor

ABSTRACT We identified the Schizosaccharomyces pombe mex67 gene (spmex67) as a multicopy suppressor of rae1-167 nup184-1 synthetic lethality and the rae1-167 tsmutation. spMex67p, a 596-amino-acid-long protein, has considerable sequence similarity to the Saccharomyces cerevisiae Mex67p (scMex67p) and human Tap. In contrast toscMEX67, spmex67 is essential for neither growth nor nuclear export of mRNA. However, an spmex67 null mutation (Δmex67) is synthetically lethal with therae1-167 mutation and accumulates poly(A)+ RNA in the nucleus. We identified a central region (149 to 505 amino acids) within spMex67p that associates with a complex containing Rae1p that complements growth and mRNA export defects of therae1-167 Δmex67 synthetic lethality. This region is devoid of RNA-binding, N-terminal nuclear localization, and the C-terminal nuclear pore complex-targeting regions. The (149–505)-green fluorescent protein (GFP) fusion is found diffused throughout the cell. Overexpression of spMex67p inhibits growth and mRNA export and results in the redistribution of the diffused localization of the (149–505)-GFP fusion to the nucleus and the nuclear periphery. These results suggest that spMex67p competes for essential mRNA export factor(s). Finally, we propose that the 149–505 region of spMex67p could act as an accessory factor in Rae1p-dependent transport and that spMex67p participates at various common steps with Rae1p export complexes in promoting the export of mRNA.

scholarly journals Alpha beta-crystallin expression and presentation following infection with murine gammaherpesvirus 68

Autoimmunity ◽  
2013 ◽  
Vol 46 (6) ◽  
pp. 399-408 ◽  
Author(s):  
Vinita S. Chauhan ◽  
Daniel A. Nelson ◽  
Ian Marriott ◽  
Kenneth L. Bost
Keyword(s):  
Murine Gammaherpesvirus ◽  
Alpha Beta ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

scholarly journals Two Kinetic Patterns of Epitope-Specific CD8 T-Cell Responses following Murine Gammaherpesvirus 68 Infection

2010 ◽  
Vol 84 (6) ◽  
pp. 2881-2892 ◽  
Author(s):  
Michael L. Freeman ◽  
Kathleen G. Lanzer ◽  
Tres Cookenham ◽  
Bjoern Peters ◽  
John Sidney ◽  
...  
Keyword(s):  
T Cell ◽  
Expression Patterns ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Immune Control ◽  
Murine Gammaherpesvirus ◽  
Cell Responses ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT Murine gammaherpesvirus 68 (γHV68) provides an important experimental model for understanding mechanisms of immune control of the latent human gammaherpesviruses. Antiviral CD8 T cells play a key role throughout three separate phases of the infection: clearance of lytic virus, control of the latency amplification stage, and prevention of reactivation of latently infected cells. Previous analyses have shown that T-cell responses to two well-characterized epitopes derived from ORF6 and ORF61 progress with distinct kinetics. ORF6487-specific cells predominate early in infection and then decline rapidly, whereas ORF61524-specific cells continue to expand through early latency, due to sustained epitope expression. However, the paucity of identified epitopes to this virus has limited our understanding of the overall complexities of CD8 T-cell immune control throughout infection. Here we screened 1,383 predicted H-2b-restricted peptides and identified 33 responses, of which 21 have not previously been reported. Kinetic analysis revealed a spectrum of T-cell responses based on the rapidity of their decline after the peak acute response that generally corresponded to the expression patterns of the two previously characterized epitopes. The slowly declining responses that were maintained during latency amplification proliferated more rapidly and underwent maturation of functional avidity over time. Furthermore, the kinetics of decline was accelerated following infection with a latency-null mutant virus. Overall, the data show that γHV68 infection elicits a highly heterogeneous CD8 T-cell response that segregates into two distinctive kinetic patterns controlled by differential epitope expression during the lytic and latency amplification stages of infection.

scholarly journals The Gammaherpesvirus Chemokine Binding Protein Binds to the N Terminus of CXCL8

2003 ◽  
Vol 77 (15) ◽  
pp. 8588-8592 ◽  
Author(s):  
Louise M. C. Webb ◽  
Ian Clark-Lewis ◽  
Antonio Alcami
Keyword(s):  
Receptor Binding ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Binding Protein ◽  
Sequence Similarity ◽  
Structural Requirements ◽  
Murine Gammaherpesvirus ◽  
N Terminus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT Viruses encode proteins that disrupt chemokine responses. The murine gammaherpesvirus 68 gene M3 encodes a chemokine binding protein (vCKBP-3) which has no sequence similarity to chemokine receptors but inhibits chemokine receptor binding and activity. We have used a panel of CXCL8 analogs to identify the structural requirements for CXCL8 to bind to vCKBP-3 in a scintillation proximity assay. Our data suggest that vCKBP-3 acts by mimicking the binding of chemokine receptors to CXCL8.

scholarly journals Identification and functional characterization of the left origin of lytic replication of murine gammaherpesvirus 68

Virology ◽  
2009 ◽  
Vol 387 (2) ◽  
pp. 285-295 ◽  
Author(s):  
Danyang Gong ◽  
Jing Qi ◽  
Vaithilingaraja Arumugaswami ◽  
Ren Sun ◽  
Hongyu Deng
Keyword(s):  
Functional Characterization ◽  
Lytic Replication ◽  
Murine Gammaherpesvirus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

Altered host response to murine gammaherpesvirus 68 infection in mice lacking the tachykinin 1 gene and the receptor for substance P

Neuropeptides ◽  
2011 ◽  
Vol 45 (1) ◽  
pp. 49-53 ◽  
Author(s):  
John P. Quinn ◽  
Anja Kipar ◽  
David J. Hughes ◽  
Elaine Bennett ◽  
Helen Cox ◽  
...  
Keyword(s):  
Substance P ◽  
Host Response ◽  
Murine Gammaherpesvirus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68
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