scholarly journals Distinct Domains in ORF52 Tegument Protein Mediate Essential Functions in Murine Gammaherpesvirus 68 Virion Tegumentation and Secondary Envelopment

2011 ◽  
Vol 86 (3) ◽  
pp. 1348-1357 ◽  
Author(s):  
L. Wang ◽  
H. Guo ◽  
N. Reyes ◽  
S. Lee ◽  
E. Bortz ◽  
...  
Keyword(s):  
Tegument Protein ◽  
Murine Gammaherpesvirus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

scholarly journals Murine Gammaherpesvirus 68 Open Reading Frame 75c Tegument Protein Induces the Degradation of PML and Is Essential for Production of Infectious Virus

2008 ◽  
Vol 82 (16) ◽  
pp. 8000-8012 ◽  
Author(s):  
Paul D. Ling ◽  
Jie Tan ◽  
Jaturong Sewatanon ◽  
RongSheng Peng
Keyword(s):  
Infectious Virus ◽  
Nuclear Body ◽  
Tegument Protein ◽  
Suitable Model ◽  
Virus Infections ◽  
Reading Frame ◽  
Murine Gammaherpesvirus ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT Promyelocytic Leukemia nuclear body (PML NB) proteins mediate an intrinsic cellular host defense response against virus infections. Herpesviruses express proteins that modulate PML or PML-associated proteins by a variety of strategies, including degradation of PML or relocalization of PML NB proteins. The consequences of PML-herpesvirus interactions during infection in vivo have yet to be investigated in detail, largely because of the species-specific tropism of many human herpesviruses. Murine gammaherpesvirus 68 (γHV68) is emerging as a suitable model to study basic biological questions of virus-host interactions because it naturally infects mice. Therefore, we sought to determine whether γHV68 targets PML NBs as part of its natural life cycle. We found that γHV68 induces PML degradation through a proteasome-dependent mechanism and that loss of PML results in more robust virus replication in mouse fibroblasts. Surprisingly, γHV68-mediated PML degradation was mediated by the virion tegument protein ORF75c, which shares homology with the cellular formylglycinamide ribotide amidotransferase enzyme. In addition, we show that ORF75c is essential for production of infectious virus. ORF75 homologs are conserved in all rhadinoviruses but so far have no assigned functions. Our studies shed light on a potential role for this unusual protein in rhadinovirus biology and suggest that γHV68 will be a useful model for investigation of PML-herpesvirus interactions in vivo.

scholarly journals Tegument Protein ORF45 Plays an Essential Role in Virion Morphogenesis of Murine Gammaherpesvirus 68

2016 ◽  
Vol 90 (16) ◽  
pp. 7587-7592 ◽  
Author(s):  
Xing Jia ◽  
Sheng Shen ◽  
Ying Lv ◽  
Ziwei Zhang ◽  
Haitao Guo ◽  
...  
Keyword(s):  
Essential Role ◽  
Ultrastructural Localization ◽  
Tegument Protein ◽  
Murine Gammaherpesvirus ◽  
Tegument Proteins ◽  
Virion Morphogenesis ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

Tegument proteins play critical roles in herpesvirus morphogenesis. ORF45 is a conserved tegument protein of gammaherpesviruses; however, its role in virion morphogenesis is largely unknown. In this work, we determined the ultrastructural localization of murine gammaherpesvirus 68 (MHV-68) ORF45 and found that this protein was incorporated into virions around the site of host-derived vesicles. Notably, the absence of ORF45 inhibited nucleocapsid egress and blocked cytoplasmic virion maturation, demonstrating that ORF45 is essential for MHV-68 virion morphogenesis.

scholarly journals Structural and Functional Studies of the Abundant Tegument Protein ORF52 from Murine Gammaherpesvirus 68

2007 ◽  
Vol 282 (43) ◽  
pp. 31534-31541 ◽  
Author(s):  
Jordi Benach ◽  
Lili Wang ◽  
Yang Chen ◽  
Chi Kent Ho ◽  
Shaoying Lee ◽  
...  
Keyword(s):  
Tegument Protein ◽  
Murine Gammaherpesvirus ◽  
Functional Studies ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

scholarly journals Murine Gammaherpesvirus 68 ORF52 Encodes a Tegument Protein Required for Virion Morphogenesis in the Cytoplasm

2007 ◽  
Vol 81 (18) ◽  
pp. 10137-10150 ◽  
Author(s):  
Eric Bortz ◽  
Lili Wang ◽  
Qingmei Jia ◽  
Ting-Ting Wu ◽  
Julian P. Whitelegge ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Cultured Cells ◽  
Artificial Chromosome ◽  
Tegument Protein ◽  
Flag Epitope ◽  
Murine Gammaherpesvirus ◽  
Virion Morphogenesis ◽  
Virion Envelope ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT The tegument, a semiordered matrix of proteins overlying the nucleocapsid and underlying the virion envelope, in viruses in the gamma subfamily of Herpesviridae is poorly understood. Murine gammaherpesvirus 68 (MHV-68) is a robust model for studying gammaherpesvirus virion structure, assembly, and composition, as MHV-68 efficiently completes the lytic phase and productively infects cultured cells. We have found that MHV-68 ORF52 encodes an abundant tegument protein conserved among gammaherpesviruses. Detergent sensitivity experiments revealed that the MHV-68 ORF52 protein is more tightly bound to the virion nucleocapsid than the ORF45 tegument protein but could be dissociated from particles that retained the ORF65 small capsomer protein. ORF52, tagged with enhanced green fluorescent protein or FLAG epitope, localized to the cytoplasm. A recombinant MHV-68 bacterial artificial chromosome mutant with a nonsense mutation incorporated into ORF52 exhibited viral DNA replication, expression of late lytic genes, and capsid assembly and packaging at levels near those of the wild type. However, the MHV-68 ORF52-null virus was deficient in the assembly and release of infectious virion particles. Instead, partially tegumented capsids produced by the ORF52-null mutant accumulated in the cytoplasm, containing conserved capsid proteins, the ORF64 and ORF67 tegument proteins, but virtually no ORF45 tegument protein. Thus, ORF52 is essential for the tegumentation and egress of infectious MHV-68 particles in the cytoplasm, suggesting an important conserved function in gammaherpesvirus virion morphogenesis.

scholarly journals A Gammaherpesvirus Ubiquitin-Specific Protease Is Involved in the Establishment of Murine Gammaherpesvirus 68 Infection

2009 ◽  
Vol 83 (20) ◽  
pp. 10644-10652 ◽  
Author(s):  
Sara Gredmark-Russ ◽  
Marisa K. Isaacson ◽  
Lisa Kattenhorn ◽  
Evelyn J. Cheung ◽  
Nicki Watson ◽  
...  
Keyword(s):  
Acute Infection ◽  
Mutant Virus ◽  
Tegument Protein ◽  
Murine Gammaherpesvirus ◽  
Enzymatic Function ◽  
Significant Difference ◽  
Gammaherpesvirus 68 ◽  
Murine Gammaherpesvirus 68

ABSTRACT Murine gammaherpesvirus 68 (MHV-68) contains a ubiquitin (Ub)-specific cysteine protease (USP) domain embedded within the large tegument protein ORF64, as do all other herpesviruses. The biological role of this protease is still unclear, but for the alphaherpesvirus Marek's disease virus, its USP is involved in T-cell lymphoma formation. We here study the role of the MHV-68 USP, encoded by ORF64. By constructing a mutant virus with a single cysteine-to-alanine replacement in the active site of ORF64, we demonstrate that the USP activity of ORF64 is abolished. The mutant virus replicates less efficiently in vitro, and plaque size is reduced compared to that of a revertant virus. Electron microscopy of infected cells did not reveal any obvious differences in virion morphogenesis or differences in egress for the mutant and revertant viruses. Intraperitoneal infection of C57/BL6 mice demonstrates that the mutant virus is generally cleared by day 7, indicating a role for the USP in the persistence of MHV-68 infection or efficient replication. However, the USP activity in MHV-68 is unlikely to be involved in the establishment of latency or reactivation, since we observed no significant difference in viral DNA genome copy number in the spleen or in the number of cells that reactivate MHV-68 from latency. Our results for MHV-68 ORF64 are consistent with an enzymatic function of the tegument protein that is beneficial to the virus during acute infection, particularly in vivo.

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.

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