| gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected b lymphocytes. | gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected b cells in vivo. recent evidence has linked plasma cell differentiation with reactivati ... | 2009 | 19956661 |
| induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency. | human gammaherpesviruses, epstein-barr virus, and human herpesvirus 8/kaposi's sarcoma-associated herpesvirus are important pathogens associated with diseases, including lymphomas and other malignancies. murine gammaherpesvirus 68 (mhv-68) is used as an experimental model system to study the host immune control of infection and explore novel vaccine strategies based on latency-deficient live viruses. we studied the properties and the potential of a recombinant mhv-68 (ac-rta) in which the genes ... | 2010 | 20015983 |
| two kinetic patterns of epitope-specific cd8 t-cell responses following murine gammaherpesvirus 68 infection. | murine gammaherpesvirus 68 (gammahv68) 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 p ... | 2010 | 20053740 |
| murine gammaherpesvirus 68 has evolved gamma interferon and stat1-repressible promoters for the lytic switch gene 50. | cytokines regulate viral gene expression with important consequences for viral replication and pathogenesis. gamma interferon (ifn-gamma) is a key regulator of chronic murine gammaherpesvirus 68 (gammahv68) infection and a potent inhibitor of gammahv68 reactivation from latency. macrophages are the cell type that is responsive to the ifn-gamma-mediated control of gammahv68 reactivation; however, the molecular mechanism of this ifn-gamma action is undefined. here we report that ifn-gamma inhibits ... | 2010 | 20071569 |
| pathogenesis of a model gammaherpesvirus in a natural host. | murine gammaherpesvirus 68 (mhv-68) infection of laboratory mice (mus musculus) is an established model of gammaherpesvirus pathogenesis. the fact that m. musculus is not a host in the wild prompted us to reassess mhv-68 infection in wood mice (apodemus sylvaticus), a natural host. here, we report significant differences in mhv-68 infection in the two species: (i) following intranasal inoculation, mhv-68 replicated in the lungs of wood mice to levels approximately 3 log units lower than in balb/ ... | 2010 | 20130062 |
| latent herpesvirus infection arms nk cells. | natural killer (nk) cells were identified by their ability to kill target cells without previous sensitization. however, without an antecedent "arming" event, nk cells can recognize, but are not equipped to kill, target cells. how nk cells become armed in vivo in healthy hosts is unclear. because latent herpesviruses are highly prevalent and alter multiple aspects of host immunity, we hypothesized that latent herpesvirus infection would arm nk cells. here we show that nk cells from mice latently ... | 2010 | 20139098 |
| three-dimensional visualization of gammaherpesvirus life cycle in host cells by electron tomography. | gammaherpesviruses are etiologically associated with human tumors. a three-dimensional (3d) examination of their life cycle in the host is lacking, significantly limiting our understanding of the structural and molecular basis of virus-host interactions. here, we report the first 3d visualization of key stages of the murine gammaherpesvirus 68 life cycle in nih 3t3 cells, including viral attachment, entry, assembly, and egress, by dual-axis electron tomography. in particular, we revealed the tra ... | 2010 | 20152152 |
| tumors induced by murine herpesvirus 60 or by cell line nb-78 derived from a tumor induced by murine herpesvirus 78 show presence of the inducing viruses. | murine herpesviruses 60 and 78 (mhv-60, mhv-78), closely related to mouse herpesvirus strain 68 (mhv-68), are oncogenic lymphotropic gammaherpesviruses, which may serve as models for study of human oncogenic gammaherpesviruses such as epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv). in this work, we attempted to detect an analog of the mhv-68 orf73 gene in tumors induced in mice either directly by mhv-60 or indirectly by mhv-78 via inoculation of nb-78 cells derived f ... | 2010 | 20201615 |
| murine gammaherpesvirus 68 lana is essential for virus reactivation from splenocytes but not long-term carriage of viral genome. | orf73, which encodes the latency-associated nuclear antigen (lana), is a conserved gamma-2-herpesvirus gene. the murine gammaherpesvirus 68 (mhv68) lana (mlana) is critical for efficient virus replication and the establishment of latent infection following intranasal inoculation. to test whether the initial host immune response limits the capacity of mlana-null virus to traffic to and establish latency in the spleen, we infected type i interferon receptor knockout (ifn-alpha/betar(-/-)) mice via ... | 2010 | 20444892 |
| use of a virus-encoded enzymatic marker reveals that a stable fraction of memory b cells expresses latency-associated nuclear antigen throughout chronic gammaherpesvirus infection. | an integral feature of gammaherpesvirus infections is the ability to establish lifelong latency in b cells. during latency, the viral genome is maintained as an extrachomosomal episome, with stable maintenance in dividing cells mediated by the viral proteins epstein-barr nuclear antigen 1 (ebna-1) for epstein-barr virus and latency-associated nuclear antigen (lana) for kaposi's sarcoma-associated herpesvirus. it is believed that the expression of episome maintenance proteins is turned off in the ... | 2010 | 20484501 |
| interleukin-27 expression following infection with the murine gammaherpesvirus 68. | il-27 is a heterodimeric cytokine composed of p28 and epstein barr virus induced gene 3 (ebi3) protein subunits. in the present study, we questioned whether murine gammaherpesvirus 68 (hv-68) could induce expression of ebi3, p28, and il-27 in this mouse model of an ebv-like infection. cultured macrophages and dendritic cells exposed to hv-68 upregulated p28 mrna expression and increased secretion of the p28 and il-27 (p28+ebi3) proteins. b220(+) and cd11b(+) cells also upregulated p28 mrna expre ... | 2010 | 20493722 |
| vaccination with murid herpesvirus-4 glycoprotein b reduces viral lytic replication but does not induce detectable virion neutralization. | herpesviruses characteristically disseminate from immune hosts. therefore in the context of natural infection, antibody neutralizes them poorly. murid herpesvirus-4 (muhv-4) provides a tractable model with which to understand gammaherpesvirus neutralization. muhv-4 virions blocked for cell binding by immune sera remain infectious for igg-fc receptor(+) myeloid cells, so broadly neutralizing antibodies must target the virion fusion complex - glycoprotein b (gb) or gh/gl. while gb-specific neutral ... | 2010 | 20519454 |
| cd4 t-cell help programs a change in cd8 t-cell function enabling effective long-term control of murine gammaherpesvirus 68: role of pd-1-pd-l1 interactions. | we previously showed that agonistic antibodies to cd40 could substitute for cd4 t-cell help and prevent reactivation of murine gammaherpesvirus 68 (mhv-68) in the lungs of major histocompatibility complex (mhc) class ii(-/-) (cii(-/-)) mice, which are cd4 t cell deficient. although cd8 t cells were required for this effect, no change in their activity was detected in vitro. a key question was whether anti-cd40 treatment (or cd4 t-cell help) changed the function of cd8 t cells or another cell typ ... | 2010 | 20534854 |
| the murine gammaherpesvirus-68 chemokine-binding protein m3 inhibits experimental autoimmune encephalomyelitis. | chemokines are critical mediators of immune cell entry into the central nervous system (cns), as occurs in neuroinflammatory disease such as multiple sclerosis. chemokines are also implicated in the immune response to viral infections. many viruses encode proteins that mimic or block chemokine actions, in order to evade host immune responses. the murine gammaherpesvirus-68 encodes a chemokine-binding protein called m3, which has unique biochemical features that enable it to bind to and inhibit a ... | 2010 | 20537410 |
| comparative study of murid gammaherpesvirus 4 infection in mice and in a natural host, bank voles. | gammaherpesviruses are archetypal pathogenic persistent viruses. the known human gammaherpesviruses (epstein-barr virus and kaposi's sarcoma-associated herpesvirus) are host-specific and therefore lack a convenient in vivo infection model. this makes related animal gammaherpesviruses an important source of information. infection by murid herpesvirus 4 (muhv-4), a virus originally isolated from bank voles (myodes glareolus), was studied here. muhv-4 infection of inbred laboratory mouse strains (m ... | 2010 | 20538905 |
| redefining the genetics of murine gammaherpesvirus 68 via transcriptome-based annotation. | viral genetic studies typically focus on large open reading frames (orfs) identified during genome annotation (orf-based annotation). here we describe tools for examining viral gene expression nucleotide by nucleotide across the genome. using these tools on the 119,450 base pair (bp) genome of murine gammaherpesvirus 68 (gammahv68) allowed us to establish that gammahv68 rna expression was significantly more complex than predicted from orf-based annotation, including over 73,000 nucleotides of un ... | 2010 | 20542255 |
| an in vitro system for studying murid herpesvirus-4 latency and reactivation. | the narrow species tropisms of epstein-barr virus (ebv) and the kaposi's sarcoma -associated herpesvirus (kshv) have made murid herpesvirus-4 (muhv-4) an important tool for understanding how gammaherpesviruses colonize their hosts. however, while muhv-4 pathogenesis studies can assign a quantitative importance to individual genes, the complexity of in vivo infection can make the underlying mechanisms hard to discern. furthermore, the lack of good in vitro muhv-4 latency/reactivation systems with ... | 2010 | 20552028 |
| inhibition of nf-kappab signaling reduces virus load and gammaherpesvirus-induced pulmonary fibrosis. | idiopathic pulmonary fibrosis (ipf) is a chronic progressive lung disorder of unknown etiology. several studies have demonstrated an association between pulmonary infection with a herpesvirus and ipf. based on those observations, we have developed a mouse model in which interferon (ifn)gammar(-/-) mice infected intranasally with murine gammaherpesvirus 68 (mhv68) develop lung fibrosis. we hypothesize that viral load was a critical factor for the development of fibrosis. because nuclear factor (n ... | 2010 | 20566741 |
| vaccination against a hit-and-run viral cancer. | cancers with viral aetiologies can potentially be prevented by antiviral vaccines. therefore, it is important to understand how viral infections and cancers might be linked. some cancers frequently carry gammaherpesvirus genomes. however, they generally express the same viral genes as non-transformed cells, and differ mainly in also carrying oncogenic host mutations. infection, therefore, seems to play a triggering or accessory role in disease. the hit-and-run hypothesis proposes that cumulative ... | 2010 | 20573854 |
| dendritic cells loaded with tumor b cells elicit broad immunity against murine gammaherpesvirus 68 but fail to prevent long-term latency. | it is still unknown whether a noninfectious gammaherpesvirus vaccine is able to prevent or reduce virus persistence. this led us to use dendritic cells loaded with tumor b cells as a vaccine approach for the murine gammaherpesvirus 68 (gammahv68) model of infection. dendritic cells loaded with uv-irradiated latently infected tumor b cells induce broad, strong, and long-lasting immunity against gammahv68. dendritic cell vaccination prevents the enlargement of lymph nodes and severely limits acute ... | 2010 | 20592077 |
| identification of novel microrna-like molecules generated from herpesvirus and host trna transcripts. | we applied deep sequencing technology to small rna fractions from cells lytically infected with murine gammaherpesvirus 68 (gammahv68) in order to define in detail small rnas generated from a cluster of trna-related polycistronic structures located at the left end of the viral genome. we detected 10 new candidate micrornas (mirnas), six of which were confirmed by northern blot analysis, leaving four as provisional. in addition, we determined that previously identified and annotated viral mirna m ... | 2010 | 20660200 |
| identification and analysis of expression of novel micrornas of murine gammaherpesvirus 68. | murine gammaherpesvirus 68 (mhv-68) is closely related to epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv) and provides a small-animal model with which to study the pathogenesis of gammaherpesvirus (gammahv) infections. to completely explore the potential of the mhv-68 system for the investigation of gammahv micrornas (mirnas), it would be desirable to know the number and expression patterns of all mirnas encoded by mhv-68. by deep sequencing of small rnas, we systemat ... | 2010 | 20668074 |
| important role for the murid herpesvirus 4 ribonucleotide reductase large subunit in host colonization via the respiratory tract. | viral enzymes that process small molecules provide potential chemotherapeutic targets. a key constraint-the replicative potential of spontaneous enzyme mutants-has been hard to define with human gammaherpesviruses because of their narrow species tropisms. here, we disrupted the murid herpesvirus 4 (muhv-4) orf61, which encodes its ribonucleotide reductase (rnr) large subunit. mutant viruses showed delayed in vitro lytic replication, failed to establish infection via the upper respiratory tract, ... | 2010 | 20668075 |
| mononucleosis and antigen-driven t cell responses have different requirements for interleukin-2 signaling in murine gammaherpesvirus infection. | interleukin-2 (il-2) has been implicated as being necessary for the optimal formation of primary cd8(+) t cell responses against various pathogens. here we have examined the role that il-2 signaling plays in several aspects of a cd8(+) t cell response against murine gammaherpesvirus 68 (mhv-68). exposure to mhv-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. our study indicates that cd25 is necessary for optimal expan ... | 2010 | 20686022 |
| placental viral infection sensitizes to endotoxin-induced pre-term labor: a double hit hypothesis. | among pregnant women, acquired viral infections with a concurrent bacterial infection is a detrimental factor associated to poor prognosis. we evaluate the effect of a viral infection that does not lead to pre-term labor on the response to low doses of lipopolysaccharide (lps). our objectives were (i) to characterize the effect of a viral infection concurrent with exposure to microbial products on pregnancy outcome and (ii) to characterize the placental and fetal immune responses to the viral se ... | 2011 | 20712808 |
| prospects of a novel vaccination strategy for human gamma-herpesviruses. | due to the oncogenic potential associated with persistent infection of human gamma-herpesviruses, including epstein-barr virus (ebv or hhv-4) and kaposi's sarcoma-associated herpesvirus (kshv or hhv-8), vaccine development has focused on subunit vaccines. however, the results using an animal model of mouse infection with a related rodent virus, murine gamma-herpesvirus 68 (mhv-68, γhv-68, or muhv-4), have shown that the only effective vaccination strategy is based on live attenuated viruses, inc ... | 2010 | 20717741 |
| histone deacetylases and the nuclear receptor corepressor regulate lytic-latent switch gene 50 in murine gammaherpesvirus 68-infected macrophages. | gammaherpesviruses are important oncogenic pathogens that transit between lytic and latent life cycles. silencing the lytic gene expression program enables the establishment of latency and a lifelong chronic infection of the host. in murine gammaherpesvirus 68 (mhv68, γhv68), essential lytic switch gene 50 controls the interchange between lytic and latent gene expression programs. however, negative regulators of gene 50 expression remain largely undefined. we report that the mhv68 lytic cycle is ... | 2010 | 20719946 |
| immature and transitional b cells are latency reservoirs for a gammaherpesvirus. | gammaherpesviruses, including kaposi's sarcoma-associated herpesvirus (kshv; also known as human herpesvirus 8 [hhv-8]), epstein-barr virus (ebv), and murine gammaherpesvirus 68 (mhv68; also known as gammaherpesvirus 68 [γhv68] or murine herpesvirus 4 [muhv-4]), establish lifelong latency in the resting memory b cell compartment. however, little is known about how this reservoir of infected mature b cells is maintained for the life of the host. in the context of a normal immune system, the matur ... | 2010 | 20926565 |
| involvement of tlr2 in recognition of acute gammaherpesvirus-68 infection. | toll-like receptors (tlrs) play a crucial role in the activation of innate immunity in response to many viruses. we previously reported the implication of tlr2 in the recognition of epstein-barr virus (ebv) by human monocytes. because murine gammaherpesvirus-68 (mhv-68) is a useful model to study human gammaherpesvirus pathogenesis in vivo, we evaluated the importance of mouse tlr2 in the recognition of mhv-68. | 2010 | 21060793 |
| the bovine herpesvirus 4 bo10 gene encodes a nonessential viral envelope protein that regulates viral tropism through both positive and negative effects. | all gammaherpesviruses encode a glycoprotein positionally homologous to the epstein-barr virus gp350 and the kaposi's sarcoma-associated herpesvirus (kshv) k8.1. in this study, we characterized the positional homologous glycoprotein of bovine herpesvirus 4 (bohv-4), encoded by the bo10 gene. we identified a 180-kda gene product, gp180, that was incorporated into the virion envelope. a bo10 deletion virus was viable but showed a growth deficit associated with reduced binding to epithelial cells. ... | 2010 | 21068242 |
| altered host response to murine gammaherpesvirus 68 infection in mice lacking the tachykinin 1 gene and the receptor for substance p. | the tachykinins are implicated in neurogenic inflammation and the neuropeptide substance p in particular has been shown to be a proinflammatory mediator. a role for the tachykinins in host response to viral infection has been previously demonstrated using either tac1- or nk1 receptor-deficient transgenic mice. however, due to redundancy in the peptide-receptor complexes we wished determine whether a deficiency in tac1 and nk1(r) in combination exhibited an enhanced phenotype. tac1 and nk1(r)-def ... | 2010 | 21106239 |
| in vivo activation of toll-like receptor-9 induces an age-dependent abortive lytic cycle reactivation of murine gammaherpesvirus-68. | infection of mice with murine gammaherpesvirus-68 (γhv-68) serves as a model to understand the pathogenesis of persistent viral infections, including the potential for co-infections to modulate viral latency. we have previously found that infection of neonates (8-day-old mice) with γhv-68 resulted in a high level of persistence of the virus in the lungs as well as the spleen, in contrast to infection of adult mice, for which long-term latency was only readily detected in the spleen. in this stud ... | 2010 | 21142440 |
| construction and characterization of an infectious murine gammaherpesivrus-68 bacterial artificial chromosome. | here we describe the cloning of a sequenced wums isolate of murine gammaherpesvirus-68 (mhv-68, γhv-68, also known as muhv-4) as a bacterial artificial chromosome (bac). we engineered the insertion of the bac sequence flanked by loxp sites into the left end of the viral genome before the m1 open reading frame. the infectious viruses were reconstituted following transfection of the mhv-68 bac dna into cells. the mhv-68 bac-derived virus replicated indistinguishably from the wild-type virus in cul ... | 2010 | 21197474 |
| identification and sequencing of a novel rodent gammaherpesvirus that establishes acute and latent infection in laboratory mice. | gammaherpesviruses encode numerous immunomodulatory molecules that contribute to their ability to evade the host immune response and establish persistent, lifelong infections. as the human gammaherpesviruses are strictly species specific, small animal models of gammaherpesvirus infection, such as murine gammaherpesvirus 68 (γhv68) infection, are important for studying the roles of gammaherpesvirus immune evasion genes in in vivo infection and pathogenesis. we report here the genome sequence and ... | 2011 | 21209105 |
| pathogenesis and host control of gammaherpesviruses: lessons from the mouse. | gammaherpesviruses are lymphotropic viruses that are associated with the development of lymphoproliferative diseases, lymphomas, as well as other nonlymphoid cancers. most known gammaherpesviruses establish latency in b lymphocytes. research on epstein-barr virus (ebv) and murine gammaherpesvirus 68 (mhv68/γhv68/mhv4) has revealed a complex relationship between virus latency and the stage of b cell differentiation. available data support a model in which gammaherpesvirus infection drives b cell ... | 2011 | 21219186 |
| 3,4-methylenedioxymethamphetamine (mdma) alters acute gammaherpesvirus burden and limits interleukin 27 responses in a mouse model of viral infection. | to test whether 3,4-methylenedioxymethamphetamine (mdma, "ecstasy") abuse might increase the susceptibility, or alter the immune response, to murine gammaherpesvirus 68 (hv-68) and/or bacterial lipopolysaccharide. | 2011 | 21269783 |
| sleep and fatigue in mice infected with murine gammaherpesvirus 68. | fatigue, a common symptom of many acute and chronic medical conditions, reduces both quality of life and workplace productivity and can be disabling. however, the pathophysiologic mechanisms that underlie fatigue can be difficult to study in human populations due to the patient heterogeneity, the variety of underlying causes and potential triggering events, and an inability to collect samples that may be essential to elucidation of mechanisms (e.g., brain). although the etiology of chronic fatig ... | 2011 | 21272632 |
| vertical transmission of murine gammaherpesvirus 68 in mice. | the mouse infected with murine gammaherpesvirus 68 (mhv-68) is accepted animal model for investigation of pathogenesis, oncogenesis, immunology and molecular biology of gammaherpesviruses in their natural host. however, little is known about the host range, epidemiology and pathogenesis of this natural pathogen of free-living murid rodents. therefore we addressed the question of transplacental transmission of mhv-68 from pregnant balb/c mice chronically infected with the virus to their fetuses a ... | 2011 | 21434705 |
| reconstitution of interactions of murine gammaherpesvirus 68 m11 with bcl-2 family proteins in yeast. | one of the mechanisms of defense against viral infection is induction of apoptosis in infected cells. to escape this line of protection, genomes of many viruses encode for proteins that inhibit apoptosis. murid herpesvirus 4 gene m11 encodes for homologue of cellular bcl-2 proteins that inhibits apoptosis and autophagy in infected cell. to study a role of m11 in regulation of apoptosis we have established a yeast model system in which the action of m11 together with proapoptotic proteins bax, ba ... | 2011 | 21439939 |
| chemokine binding protein m3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host. | murine ?-herpesvirus 68 (mhv-68) infection of mus musculus-derived strains of mice is an attractive model of ?-herpesvirus infection. surprisingly, however, ablation of expression of mhv-68 m3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. here we demonstrate that m3 indeed contributes significantly to mhv-68 infection, but only in the context of a natural host, the wood mouse (apodemus sylv ... | 2011 | 21445235 |
| in vivo function of the murid herpesvirus-4 ribonucleotide reductase small subunit. | the difficulty of eliminating herpesvirus carriage makes host entry a key target for infection control. however, its viral requirements are poorly defined. murid herpesvirus-4 (muhv-4) can potentially provide insights into gammaherpesvirus host entry. upper respiratory tract infection requires the muhv-4 thymidine kinase (tk) and ribonucleotide reductase large subunit (rnr-l), suggesting a need for increased nucleotide production. however, both tk and rnr-l are likely to be multifunctional. we t ... | 2011 | 21471322 |
| mhv-68 producing mifnα1 is severely attenuated in vivo and effectively protects mice against challenge with wt mhv-68. | human gammaherpesviruses such as epstein-barr virus (ebv) cause lifelong infections and associated diseases, by virtue of their ability to establish latent infection. many studies performed in the past years in murine herpesvirus 68 (mhv-68) model of infection suggested that the limited immunity generated against isolated viral components by subunit vaccines cannot counteract the multiple immune evasion strategies operated by gammaherpesviruses. indeed, a significant inhibition of long-term late ... | 2011 | 21481326 |
| the human cytomegalovirus gene products essential for late viral gene expression assemble into pre- replication complexes before viral dna replication. | the regulation of human cytomegalovirus (hcmv) late gene expression by viral proteins is poorly understood and these viral proteins could be a target for novel antivirals. hcmv open reading frames (orfs) ul79, 87, and 95 have homology with late gene transcription factors of murine gammaherpesvirus 68 orfs 18, 24, and 34, respectively. to determine whether these hcmv proteins are also essential for late gene transcription of a betaherpesvirus, we mutated hcmv orfs ul79, 87, or 95. cells were infe ... | 2011 | 21507978 |
| deep sequencing reveals direct targets of gammaherpesvirus-induced mrna decay and suggests that multiple mechanisms govern cellular transcript escape. | one characteristic of lytic infection with gammaherpesviruses, including kaposi's sarcoma-associated herpesvirus (kshv), epstein-barr virus (ebv) and murine herpesvirus 68 (mhv68), is the dramatic suppression of cellular gene expression in a process known as host shutoff. the alkaline exonuclease proteins (kshv sox, mhv-68 musox and ebv bglf5) have been shown to induce shutoff by destabilizing cellular mrnas. here we extend previous analyses of cellular mrna abundance during lytic infection to c ... | 2011 | 21573023 |
| a mechanistic basis for potent, gb-directed gammaherpesvirus neutralization. | glycoprotein b is a conserved, essential component of gammaherpes virions and so potentially vulnerable to neutralization. however, few good gb-specific neutralizing antibodies have been identified. here we show that murid herpesvirus-4 is strongly neutralized by monoclonal antibodies that recognize an epitope close to one of the gb fusion loops. antibody binding did not stop gb interacting with its cellular ligands or initiating its fusion-associated conformation change, but did stop gb resolvi ... | 2011 | 21593277 |
| suppression of tlr9 immunostimulatory motifs in the genome of a gammaherpesvirus. | multiple receptors within the innate immune system have evolved to recognize nucleic acids as signatures of viral infection. it is believed that this specificity is essential for viral detection, as viruses often lack other invariant features that can serve as suitable targets for innate receptors. one such innate receptor, tlr9, has been implicated in the detection of many dsdna viruses. in this study, we investigate the detection of murine gammaherpesvirus 68 (mhv68) by tlr9. we find that the ... | 2011 | 21666062 |
| global mrna degradation during lytic gammaherpesvirus infection contributes to establishment of viral latency. | during a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3' end processing of mrna. this host shutoff phenotype is orchestrated by the viral sox protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of sox. using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (mhv68) sox homolog, we isolated a single amino acid point mutant that is sel ... | 2011 | 21811408 |
| tlr9-induced interferon beta is associated with protection from gammaherpesvirus-induced exacerbation of lung fibrosis. | abstract: background: we have demonstrated previously that murine gammaherpesvirus 68 (gamma-hv68) infection exacerbates established pulmonary fibrosis. because tlr9 may be important in controlling the immune response to gamma-hv68 infection, we examined how tlr9 signaling effects exacerbation of fibrosis in response to viral infection using models of bleomycin- and fluorescein isothiocyanate-induced pulmonary fibrosis in wild-type (balb/c) and tlr9-/- mice. results: we demonstrate that in the a ... | 2011 | 21810214 |
| neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions. | previously, we reported that murine ?herpesvirus-68 (m1-mhv-68) induces pulmonary artery (pa) neointimal lesions in s100a4-overexpressing, but not in wild-type (c57), mice. lesions were associated with heightened lung elastase activity and pa elastin degradation. we now investigate a direct relationship between elastase and pa neointimal lesions, the nature and source of the enzyme, and its presence in clinical disease. we found an association exists between the percentage of pas with neointimal ... | 2011 | 21763677 |
| ccaat/enhancer binding proteins play a role in orilyt-dependent genome replication during mhv-68 de novo infection. | murine gammaherpesvirus 68 (mhv-68), a member of the gammaherpesvirus family, replicates robustly in permissive cell lines and is able to infect laboratory mice. mhv-68 has emerged as a model for studying the basic aspects of viral replication and host-virus interactions of its human counterparts. herpesvirus genome replication is mediated through a cis-element in the viral genome called the origin of lytic replication (orilyt). a family of transcription factors, ccaat/enhancer binding proteins ... | 2011 | 21748596 |
| strain-dependent requirement for ifn-+¦ for respiratory control and immunotherapy in murine gammaherpesvirus infection. | abstract interferon-+¦ (ifn-+¦) and perforin (pfp) are important effector mechanisms used by cd8 t cells to clear virus-infected cells. in this study, we used ifn-+¦/pfp double knockout mice to address if these two effector molecules play redundant roles in the control of acute infection with murine gammaherpesvirus-68 (mhv-68) in balb/c mice. perforin knockout (ko) mice and wild-type mice cleared infectious virus from the lungs, even following high-dose infection. however, the ifn-+¦ ko and ifn ... | 2011 | 21830899 |
| a role for dna-dependent activator of interferon regulatory factor in the recognition of herpes simplex virus type 1 by glial cells. | abstract: | 2011 | 21838860 |
| molecular detection of murine herpesvirus 68 in ticks feeding on free-living reptiles. | the mhv-68 (designed as murid herpesvirus 4 (muhv 4) strain 68) isolated from two rodents, myodes glareolus and apodemus flavicollis, is considered as a natural pathogen of free-living murid rodents. recently, the detection of mhv antibodies in the blood of animals living in the same biotope as mhv-infected mice has suggested that ticks may have a role in the transmission of this pathogen. ixodes ricinus is one the most abundant tick species in europe known to transmit multiple pathogens causing ... | 2011 | 21732020 |
| murid herpesvirus-4 exploits dendritic cells to infect b cells. | dendritic cells (dcs) play a central role in initiating immune responses. some persistent viruses infect dcs and can disrupt their functions in vitro. however, these viruses remain strongly immunogenic in vivo. thus what role dc infection plays in the pathogenesis of persistent infections is unclear. here we show that a persistent, b cell-tropic gamma-herpesvirus, murid herpesvirus-4 (muhv-4), infects dcs early after host entry, before it establishes a substantial infection of b cells. dc-specif ... | 2011 | 22102809 |
| Dynamic association of gammaherpesvirus DNA with core histone during de novo lytic infection of primary cells. | Association of herpesvirus DNA with histones has important implications for lytic and latent infections; thus herpesviruses arbitrate interactions with histones to productively infect host cells. While regulation of alpha and betaherpesvirus chromatin during lytic infection has been actively investigated, very little is known about interaction of gammaherpesvirus DNA with histones upon de novo lytic infection. Murine gammaherpesvirus-68 (MHV68) is a rodent pathogen that offers a tractable system ... | 2011 | 22018782 |
| Persistent infection of a gammaherpesvirus in the central nervous system. | Human gammaherpesvirus infections of the central nervous system (CNS) have been linked to various neurological diseases. Murine gammaherpesvirus 68 (MHV-68), genetically related and biologically similar to human gammaherpesviruses, infects the CNS in laboratory mice. However, viral persistency of MHV-68 has not been studied following CNS infection. In this study, we undertook the noninvasive bioluminescence imaging of a recombinant MHV-68 expressing the firefly luciferase (M3FL) to monitor virus ... | 2011 | 22169075 |
| distinct domains in orf52 tegument protein mediate essential functions in murine gammaherpesvirus 68 virion tegumentation and secondary envelopment. | epstein-barr virus and kaposi's sarcoma-associated herpesvirus are etiologically associated with several types of human malignancies. however, as these two human gammaherpesviruses do not replicate efficiently in cultured cells, the morphogenesis of gammaherpesvirus virions is poorly understood. murine gammaherpesvirus 68 (mhv-68) provides a tractable model to define common, conserved features of gammaherpesvirus biology. orf52 of mhv-68 is conserved among gammaherpesviruses. we have previously ... | 2011 | 22090138 |
| a gammaherpesvirus cooperates with interferon-alpha/beta-induced irf2 to halt viral replication, control reactivation, and minimize host lethality. | the gammaherpesviruses, including epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv), establish latency in memory b lymphocytes and promote lymphoproliferative disease in immunocompromised individuals. the precise immune mechanisms that prevent gammaherpesvirus reactivation and tumorigenesis are poorly defined. murine gammaherpesvirus 68 (mhv68) is closely related to ebv and kshv, and type i (alpha/beta) interferons (ifnαβ) regulate mhv68 reactivation from both b cells a ... | 2011 | 22114555 |
| partial genome sequence of murine gammaherpesvirus 72 and its analysis. | murine gammaherpesvirus 68 (mhv-68)-infected mouse is a well known model for studies of epstein-barr virus (ebv)-related lymphoproliferative diseases (lpd). murine gammaherpesvirus 72 (mhv-72) has been considered a close relative of mhv-68 but its replication in murine mammary gland cells and kinetics of infection of mice were found to be different. pathological studies of a long-term-infection of mice revealed a similar or higher malignancy development rate in mhv-72-infected mice as compared w ... | 2011 | 22149497 |
| de novo infection of b cells during murine gammaherpesvirus 68 latency. | the mechanisms by which gammaherpesviruses maintain latency are unclear. here we used a murine gammaherpesvirus model to show that previously uninfected b cells in immunocompetent mice can acquire virus during latency. in vivo depletion of t cells allowed viral reactivation, as measured by increased viral loads, but not enhanced transfer of virus to new cells. in the absence of both immune t cells and antibody following the transfer of latently infected cells into naïve animals, there was robust ... | 2011 | 21849446 |
| virally-induced upregulation of heparan sulfate on b cells via the action of type i ifn. | cell surface heparan sulfate (hs) is an important coreceptor for many cytokines, chemokines, and growth factors. in this study, we report that splenic murine b cells express very little hs and that upon infection with either gammaherpesvirus (murine gammaherpesvirus 68) or betaherpesvirus (murine cytomegalovirus), hs is rapidly upregulated at the surface of b cells. hs upregulation was not observed in mice deficient for the type i ifn (ifn-i) receptor. additionally, treatment of wild-type mice w ... | 2011 | 22048770 |
| murine γ-herpesvirus 68 evades host cytokine production via rta-induced rela degradation. | cytokines play crucial roles in curtailing the propagation and spread of pathogens within the host. as obligate pathogens, γ-herpesviruses have evolved a plethora of mechanisms to evade host immune responses. we have previously shown that murine γ-herpesvirus 68 (γhv68) induces the degradation of rela, an essential subunit of the transcriptionally active nfκb dimer, to evade cytokine production. here, we report that the immediately early gene product of γhv68, replication transactivator (rta), f ... | 2011 | 22130545 |
| specific mutation of a γ-herpesvirus-expressed antigen in response to cd8 t cell selection in vivo. | herpesviruses are thought to be highly genetically stable and their use as vaccine vectors has been proposed. however, studies of the human γ-herpesvirus, epstein-barr virus, have found viral isolates containing mutations in hla class i-restricted epitopes. using murine γ-herpesvirus 68 expressing ovalbumin (ova), we examined the stability of a γ-herpesvirus antigenic locus under strong cd8 t cell selection in vivo. ova-specific cd8 t cells selected viral isolates containing mutations in the ova ... | 2011 | 22171269 |
| bovine herpesvirus 4 glycoprotein l is non-essential for infectivity but triggers virion endocytosis during entry. | the core entry machinery of mammalian herpesviruses comprises glycoproteins b, h and l (gb, gh and gl). gh and gl form a heterodimer with a central role in viral membrane fusion. when archetypal alpha- or beta-herpesviruses lack gl, gh misfolds and progeny virions are non-infectious. however, the gl of the rhadinovirus murid herpesvirus 4 (muhv-4) is non-essential for infection. in order to define more generally what role gl plays in rhadinovirus infections, we disrupted its coding sequence in b ... | 2011 | 22205754 |
| Replication and transcription activator (RTA) of murine gammaherpesvirus 68 binds to an RTA-responsive element and activates the expression of ORF18. | The replication and transcription activator (RTA), mainly encoded by open reading frame 50, is an immediate-early gene product that is conserved among all characterized gammaherpesviruses. Previous studies have demonstrated that RTA proteins of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) can activate the promoter of many viral early lytic genes through direct or indirect mechanisms. Murine gammaherpesvirus 68 (MHV-68) is genetically related to KSHV and EBV, and th ... | 2011 | 21849436 |
| murine gamma-herpesvirus immortalization of fetal liver-derived b cells requires both the viral cyclin d homolog and latency-associated nuclear antigen. | human gammaherpesviruses are associated with the development of lymphoproliferative diseases and b cell lymphomas, particularly in immunosuppressed hosts. understanding the molecular mechanisms by which human gammaherpesviruses cause disease is hampered by the lack of convenient small animal models to study them. however, infection of laboratory strains of mice with the rodent virus murine gammaherpesvirus 68 (mhv68) has been useful in gaining insights into how gammaherpesviruses contribute to t ... | 2011 | 21931547 |
| the virion-associated open reading frame 49 of murine gammaherpesvirus 68 promotes viral replication both in vitro and in vivo as a derepressor of rta. | replication and transcription activator (rta), an immediate-early gene, is a key molecular switch to evoke lytic replication of gammaherpesviruses. open reading frame 49 (orf49) is conserved among gammaherpesviruses and shown to cooperate with rta in regulating virus lytic replication. here we show a molecular mechanism and in vivo functions of murine gammaherpesvirus 68 (mhv-68 or γhv-68) orf49. mhv-68 orf49 was transcribed and translated as a late gene. the orf49 protein was associated with a ... | 2012 | 22090108 |
| open reading frame 23 of murine gammaherpesvirus 68 is nonessential for in vitro and in vivo infection. | although open reading frame (orf) 23 is conserved among gammaherpesviruses, its role during infection is not known. here, we studied the expression of orf23 of murine gammaherpesvirus 68 (mhv-68) and its role during infection. orf23 mrna was detected in infected cells as a late transcript. the orf23 protein product could be expressed and detected as an n-terminally flag-tagged protein by western blot and indirect immunofluorescence. to investigate the role of orf23 in the infection cycle of a ga ... | 2012 | 22258865 |
| zap inhibits murine gammaherpesvirus 68 orf64 expression and is antagonized by rta. | zinc finger antiviral protein (zap) is an interferon-inducible host antiviral factor that specifically inhibits the replication of certain viruses, including hiv-1 and ebola virus. zap functions as a dimer formed through intermolecular interactions of its n-terminal tails. zap binds directly to specific viral mrnas and inhibits their expression by repressing translation and/or promoting degradation of the target mrna. zap is not a universal antiviral factor, since some viruses grow normally in z ... | 2012 | 23255809 |
| zinc finger antiviral protein inhibits murine gammaherpesvirus 68 m2 expression and regulates viral latency in cultured cells. | zinc finger antiviral protein (zap) is a host factor that specifically inhibits the replication of certain viruses by binding to specific viral mrnas and repressing mrna expression. here we report that zap inhibits expression of murine gammaherpesvirus 68 (mhv-68) m2, which plays important roles in establishment and maintenance of viral latency. downregulation of endogenous zap in cells harboring latent mhv-68 promoted lytic replication of the virus. these results suggest that zap inhibits m2 ex ... | 2012 | 22951821 |
| autophagy genes enhance murine gammaherpesvirus 68 reactivation from latency by preventing virus-induced systemic inflammation. | host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. murine gammaherpesvirus 68 (mhv68) infection is characterized by latency in macrophages, and reactivation is inhibited by interferon-γ (ifn-γ). using a lysozyme-m-cre (lysmcre) expression system, we show that deletion of autophagy-related (atg) genes fip200, beclin 1, atg14, atg16l1, atg7, atg3, and atg5, in the myeloid compartment, inhibited mhv68 reactivation in macrophages. atg5 deficiency ... | 0 | 26764599 |
| the interferon-inducible mouse apolipoprotein l9 and prohibitins cooperate to restrict theiler's virus replication. | apolipoprotein l9b (apol9b) is an interferon-stimulated gene (isg) that has antiviral activity and is weakly expressed in primary mouse neurons as compared to other cell types. here, we show that both apol9 isoforms (apol9b and apol9a) inhibit replication of theiler's murine encephalomyelitis virus (tmev) but not replication of vesicular stomatitis virus (vsv), murid herpesvirus-4 (muhv-4), or infection by a lentiviral vector. apol9 genes are strongly expressed in mouse liver and, to a lesser ex ... | 2015 | 26196674 |
| a gammaherpesvirus bcl-2 ortholog blocks b cell receptor-mediated apoptosis and promotes the survival of developing b cells in vivo. | gammaherpesviruses such as epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv, hhv-8) establish lifelong latency in their hosts and are associated with the development of several types of malignancies, including a subset of b cell lymphomas. these viruses are thought to co-opt the process of b cell differentiation to latently infect a fraction of circulating memory b cells, resulting in the establishment of a stable latency setpoint. however, little is known about how thi ... | 2014 | 24516386 |
| subcapsular sinus macrophages limit acute gammaherpesvirus dissemination. | lymphocyte proliferation, mobility and longevity make them prime targets for virus infection. myeloid cells that process and present environmental antigens to lymphocytes are consequently an important line of defence. subcapsular sinus macrophages (ssms) filter the afferent lymph and communicate with b-cells. how they interact with b-cell-tropic viruses is unknown. we analysed their encounter with murid herpesvirus-4 (muhv-4), an experimentally accessible gammaherpesvirus related to kaposi's sar ... | 2015 | 25872742 |
| immune protection against virus challenge in aging mice is not affected by latent herpesviral infections. | latent herpesvirus infections alter immune homeostasis. to understand if this results in aging-related loss of immune protection against emerging infections, we challenged old mice carrying latent mouse cytomegalovirus (cmv), herpes simplex virus 1 (hsv-1), and/or murine gammaherpesvirus 68 (mhv-68) with influenza virus, west nile virus (wnv), or vesicular stomatitis virus (vsv). we observed no increase in mortality or weight loss compared to results seen with herpesvirus-negative counterparts a ... | 2015 | 26339051 |
| type i interferon signaling enhances cd8+ t cell effector function and differentiation during murine gammaherpesvirus 68 infection. | cd8(+) t cell responses are critical to the control of replication and reactivation associated with gammaherpesvirus infection. type i interferons (ifns) have been shown to have direct and indirect roles in supporting cd8(+) t cell development and function during viral infection; however, the role of type i interferons during latent viral infection has not been examined. mice deficient in type i ifn signaling (ifnar1(-/-) mice) have high levels of reactivation during infection with murine gammah ... | 2014 | 25253356 |
| gammaherpesvirus latency differentially impacts the generation of primary versus secondary memory cd8+ t cells during subsequent infection. | unlike laboratory animals, humans are infected with multiple pathogens, including the highly prevalent herpesviruses. the purpose of these studies was to determine the effect of gammaherpesvirus latency on t cell number and differentiation during subsequent heterologous viral infections. mice were first infected with murine gammaherpesvirus 68 (mhv68), a model of epstein-barr virus (ebv) infection, and then after latency was established, they were challenged with the armstrong strain of lymphocy ... | 2014 | 25142586 |
| stabilization of myc through heterotypic poly-ubiquitination by mlana is critical for γ-herpesvirus lymphoproliferation. | host colonization by lymphotropic γ-herpesviruses depends critically on expansion of viral genomes in germinal center (gc) b-cells. myc is essential for the formation and maintenance of gcs. yet, the role of myc in the pathogenesis of γ-herpesviruses is still largely unknown. in this study, myc was shown to be essential for the lymphotropic γ-herpesvirus muhv-4 biology as infected cells exhibited increased expression of myc signature genes and the virus was unable to expand in myc defficient gc ... | 2013 | 23950719 |
| the role of latently infected b cells in cns autoimmunity. | the onset of multiple sclerosis (ms) is caused by both genetic and environmental factors. among the environmental factors, it is believed that previous infection with epstein-barr virus (ebv) may contribute in the development of ms. ebv has been associated with other autoimmune diseases, such as systemic lupus erythematous, and cancers like burkitt's lymphoma. ebv establishes a life-long latency in b cells with occasional reactivation of the virus throughout the individual's life. the role playe ... | 2015 | 26579121 |
| murine cytomegalovirus exploits olfaction to enter new hosts. | viruses transmit via the environmental and social interactions of their hosts. herpesviruses have colonized mammals since their earliest origins, suggesting that they exploit ancient, common pathways. cytomegaloviruses (cmvs) are assumed to enter new hosts orally, but no site has been identified. we show by live imaging that murine cmv (mcmv) infects nasally rather than orally, both after experimental virus uptake and during natural transmission. replication-deficient virions revealed the primar ... | 2016 | 27118588 |
| alveolar macrophages are a prominent but nonessential target for murine cytomegalovirus infecting the lungs. | cytomegaloviruses (cmvs) infect the lungs and cause pathological damage there in immunocompromised hosts. how lung infection starts is unknown. inhaled murine cmv (mcmv) directly infected alveolar macrophages (ams) and type 2 alveolar epithelial cells (aec2s) but not type 1 alveolar epithelial cells (aec1s). in contrast, herpes simplex virus 1 infected aec1s and murid herpesvirus 4 (muhv-4) infected aec1s via ams. mcmv-infected ams prominently expressed viral reporter genes from a human cmv ie1 ... | 2015 | 26719275 |
| mouse cmv infection delays antibody class switch upon an unrelated virus challenge. | poor immune protection upon vaccination is a critical determinant of immunosenescence. latent cytomegalovirus (cmv) infection has been associated with poor antibody responses to vaccination, but a causative role for cmv in the poor immune response requires experimental evidence and thus could not be confirmed in clinical studies. to test the hypothesis that latent cmv infection causes poor antibody responses, we infected young or adult mice with mouse cmv and challenged them with vesicular stoma ... | 2014 | 24462805 |
| soluble m3 proteins of murine gammaherpesviruses 68 and 72 expressed in escherichia coli: analysis of chemokine-binding properties. | m3 protein of murine gammaherpesvirus 68 (mhv-68) was identified as a viral chemokine-binding protein 3 (vckbp-3) capable to bind a broad spectrum of chemokines and their receptors. during both acute and latent infection mhv-68 m3 protein provides a selective advantage for the virus by inhibiting the antiviral and inflammatory response. a unique mutation asp307gly was identified in the m3 protein of murine gammaherpesvirus 72 (mhv-72), localized near chemokine-binding domain. study on chemokine- ... | 2015 | 26666184 |
| b cell response to herpesvirus infection of the olfactory neuroepithelium. | viruses commonly infect the respiratory tract. analyses of host defense have focused on the lungs and the respiratory epithelium. spontaneously inhaled murid herpesvirus 4 (muhv-4) and herpes simplex virus 1 (hsv-1) instead infect the olfactory epithelium, where neuronal cilia are exposed to environmental antigens and provide a route across the epithelial mucus. we used muhv-4 to define how b cells respond to virus replication in this less well-characterized site. olfactory infection elicited ge ... | 2014 | 25253348 |
| herpesvirus delivery to the murine respiratory tract. | herpesvirus transmission is sporadic, and infection may be asymptomatic or present only with secondary lesions after dissemination. consequently host entry remains ill-understood. experimental infections can be informative, but depend on inoculations that are inherently artificial and so need validation. mice are a widely used experimental host. alert mice inhale readily small (5 μl) liquid volumes, and indian ink, luciferase or radiolabel delivered thus distributed to the nasopharynx and oropha ... | 2014 | 24928692 |
| activity and mechanism of action of hdvd, a novel pyrimidine nucleoside derivative with high levels of selectivity and potency against gammaherpesviruses. | a novel nucleoside analogue, 1-[(2s,4s-2-(hydroxymethyl)-1,3-dioxolan-4-yl]5-vinylpyrimidine-2,4(1h,3h)-dione, or hdvd, was evaluated against a wide variety of herpesviruses and was found to be a highly selective inhibitor of replication of the gammaherpesviruses kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv). hdvd had also a pronounced inhibitory activity against murine herpesvirus 68 (mhv-68) and herpes simplex virus 1 (hsv-1). in contrast, replication of herpesvir ... | 2013 | 23345517 |
| nanoparticle exposure reactivates latent herpesvirus and restores a signature of acute infection. | inhalation of environmental (nano) particles (np) as well as persistent herpesvirus-infection are potentially associated with chronic lung disease and as both are omnipresent in human society a coincidence of these two factors is highly likely. we hypothesized that np-exposure of persistently herpesvirus-infected cells as a second hit might disrupt immune control of viral latency, provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage. | 2017 | 28069010 |
| regulation of the viral life cycle by murine gammaherpesvirus 68 micrornas. | γ-herpesviruses (γhv) such as epstein-barr virus and kaposi's sarcoma-associated herpesvirus are important human pathogens involved in lymphoproliferation and tumorigenesis. murine gammaherpesvirus 68 (mhv-68, γhv-68) is an effective model for the study of γhv pathogenesis and host-virus interaction because it is closely related to human γhv. similarly to human γhv, mhv-68 encodes 15 micrornas (mirnas). although their functions remain unknown, they are thought to regulate the viral life cycle or ... | 2017 | 27837274 |
| interplay of murine gammaherpesvirus 68 with nf-kappab signaling of the host. | herpesviruses establish a chronic infection in the host characterized by intervals of lytic replication, quiescent latency, and reactivation from latency. murine gammaherpesvirus 68 (mhv68) naturally infects small rodents and has genetic and biologic parallels with the human gammaherpesviruses (ghvs), kaposi's sarcoma-associated herpesvirus and epstein-barr virus. the murine gammaherpesvirus model pathogen system provides a platform to apply cutting-edge approaches to dissect the interplay of ga ... | 2016 | 27582728 |
| the small noncoding rnas (sncrnas) of murine gammaherpesvirus 68 (mhv-68) are involved in regulating the latent-to-lytic switch in vivo. | the human gammaherpesviruses epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv), which are associated with a variety of diseases including tumors, produce various small noncoding rnas (sncrnas) such as micrornas (mirnas). like all herpesviruses, they show two stages in their life cycle: lytic replication and latency. during latency, hardly any viral proteins are expressed to avoid recognition by the immune system. thus, sncrnas might be exploited since they are less like ... | 2016 | 27561205 |
| ablation of stat3 in the b cell compartment restricts gammaherpesvirus latency in vivo. | a challenging property of gammaherpesviruses is their ability to establish lifelong persistence. the establishment of latency in b cells is thought to involve active virus engagement of host signaling pathways. pathogenic effects of these viruses during latency or following reactivation can be devastating to the host. many cancers, including those associated with members of the gammaherpesvirus family, kaposi's sarcoma-associated herpesvirus and epstein-barr virus, express elevated levels of act ... | 2016 | 27486189 |
| latency-associated nuclear antigen e3 ubiquitin ligase activity impacts gammaherpesvirus-driven germinal center b cell proliferation. | viruses have evolved mechanisms to hijack components of cellular e3 ubiquitin ligases, thus modulating the ubiquitination pathway. however, the biological relevance of such mechanisms for viral pathogenesis in vivo remains largely unknown. here, we utilized murid herpesvirus 4 (muhv-4) infection of mice as a model system to address the role of muhv-4 latency-associated nuclear antigen (mlana) e3 ligase activity in gammaherpesvirus latent infection. we show that specific mutations in the mlana so ... | 2016 | 27307564 |
| a gammaherpesvirus noncoding rna is essential for hematogenous dissemination and establishment of peripheral latency. | recent intense investigations have uncovered important functions for a diverse array of novel noncoding rna (ncrna) species, including micrornas (mirnas) and long noncoding rnas. not surprisingly, viruses from multiple families have evolved to encode their own regulatory rnas; however, the specific in vivo functions of these ncrnas are largely unknown. the human gammaherpesviruses epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv) are highly ubiquitous pathogens that are ... | 2016 | 27110595 |
| murine gammaherpesvirus 68 orf35 is required for efficient lytic replication and latency. | murine gammaherpesvirus (mhv) 68, a natural pathogen of field mice, is related to human gammaherpesviruses, epstein–barr virus (ebv; human herpesvirus 4) and kaposi’s sarcoma-associated herpesvirus (kshv; human herpesvirus 8). the orf35 of mhv-68 and its homologues of ebv and kshv are located in the gene cluster composed of orf34–orf38 in which each gene overlaps with adjacent genes. although mhv-68 orf35 was reported to be an essential gene, its function during infection is presently unknown. i ... | 2015 | 26459827 |
| host entry by gamma-herpesviruses--lessons from animal viruses? | the oncogenicity of gamma-herpesviruses (γhvs) motivates efforts to control them and their persistence makes early events key targets for intervention. human γhvs are often assumed to enter naive hosts orally and infect b cells directly. however, neither assumption is supported by direct evidence, and vaccination with the epstein-barr virus (ebv) gp350, to block virion binding to b cells, failed to reduce infection rates. thus, there is a need to re-evaluate assumptions about γhv host entry. giv ... | 2015 | 26246389 |
| gammaherpesvirus co-infection with malaria suppresses anti-parasitic humoral immunity. | immunity to non-cerebral severe malaria is estimated to occur within 1-2 infections in areas of endemic transmission for plasmodium falciparum. yet, nearly 20% of infected children die annually as a result of severe malaria. multiple risk factors are postulated to exacerbate malarial disease, one being co-infections with other pathogens. children living in sub-saharan africa are seropositive for epstein barr virus (ebv) by the age of 6 months. this timing overlaps with the waning of protective m ... | 2015 | 25996913 |
| roles of epstein-barr virus bglf3.5 gene and two upstream open reading frames in lytic viral replication in hek293 cells. | the epstein-barr virus (ebv) predominantly establishes a latent infection in b lymphocytes, but a small percentage of infected cells switch from the latent state to the lytic cycle, leading to potent viral dna replication and progeny viruses production. we here focused on a lytic gene bglf3.5, and first established bglf3.5 mutants by marker cassette insertion. unexpectedly, this insertion mutant failed to produce bglf4 protein and thus progeny production was severely inhibited. then we carefully ... | 2015 | 25965794 |
| gammaherpesvirus tegument protein orf33 is associated with intranuclear capsids at an early stage of the tegumentation process. | herpesvirus nascent capsids, after assembly in the nucleus, must acquire a variety of tegument proteins during maturation. however, little is known about the identity of the tegument proteins that are associated with capsids in the nucleus or the molecular mechanisms involved in the nuclear egress of capsids into the cytoplasm, especially for the two human gammaherpesviruses epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv), due to a lack of efficient lytic replication ... | 2015 | 25717105 |
| murine gammaherpesvirus-68 (mhv-68) is not horizontally transmitted amongst laboratory mice by cage contact. | murine gammaherpesvirus-68 (mhv-68), a natural pathogen of mice, is being evaluated as a model of epstein barr virus (ebv) infection for use in investigation of the effects of immunomodulatory therapy on herpesvirus pathogenesis in humans. immunosuppressive agents are used for treatment of a variety of autoimmune diseases as well as for prevention of tissue rejection after organ transplantation and can result in recrudescence of latent herpesvirus infections. prior to examination of mhv-68 as a ... | 2015 | 25412621 |
| murine gammaherpesvirus 68 reactivation from b cells requires irf4 but not xbp-1. | gammaherpesviruses display tropism for b cells and, like all known herpesviruses, exhibit distinct lytic and latent life cycles. one well-established observation among members of the gammaherpesvirus family is the link between viral reactivation from latently infected b cells and plasma cell differentiation. importantly, a number of studies have identified a potential role for a creb/atf family member, x-box binding protein 1 (xbp-1), in trans-activating the immediate early bzlf-1 or brlf1/gene ... | 2014 | 25078688 |