| virus-encoded micrornas facilitate gammaherpesvirus latency and pathogenesis in vivo. | gammaherpesviruses, including epstein-barr virus (ebv), kaposi sarcoma-associated herpesvirus (kshv, or hhv-8), and murine gammaherpesvirus 68 (mhv68, γhv68, or muhv-4), are b cell-tropic pathogens that each encode at least 12 micrornas (mirnas). it is predicted that these regulatory rnas facilitate infection by suppressing host target genes involved in a wide range of key cellular pathways. however, the precise contribution that gammaherpesvirus mirnas make to viral life cycle and pathogenesis ... | 2014 | 24865551 |
| expansion of murine gammaherpesvirus latently infected b cells requires t follicular help. | x linked lymphoproliferative disease (xlp) is an inherited immunodeficiency resulting from mutations in the gene encoding the slam associated protein (sap). one of the defining characteristics of xlp is extreme susceptibility to infection with epstein-barr virus (ebv), a gammaherpesvirus belonging to the genus lymphocryptovirus, often resulting in fatal infectious mononucleosis (fim). however, infection of sap deficient mice with the related murine gammaherpesvirus 68 (mhv68), a gammaherpesvirus ... | 2014 | 24789087 |
| a shutoff and exonuclease mutant of murine gammaherpesvirus-68 yields infectious virus and causes rna loss in type i interferon receptor knockout cells. | significant loss of rna followed by severely reduced cellular protein pool, a phenomenon termed host shutoff, is associated with a number of lytic virus infections and is a critical player in viral pathogenesis. until recently, viral dna exonucleases were associated only with processing of viral genomic dna and its encapsidation. however, recent observations have identified host shutoff and exonuclease function for the highly conserved viral exonucleases in γ-herpesviruses, which include kaposi' ... | 2014 | 24552788 |
| is murine gammaherpesvirus-68 (mhv-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence? | immunosuppressive agents are used for treatment of a variety of autoimmune diseases including rheumatoid arthritis (ra), systemic lupus erythematosis (sle), and psoriasis, as well as for prevention of tissue rejection after organ transplantation. recrudescence of herpesvirus infections, and increased risk of carcinogenesis from herpesvirus-associated tumors are related with immunosuppressive therapy in humans. post-transplant lymphoproliferative disorder (ptld), a condition characterized by deve ... | 2014 | 24512328 |
| baff receptor deficiency limits gammaherpesvirus infection. | lymphocyte colonization by gammaherpesviruses (γhvs) is an important target for cancer prevention. however, how it works is not clear. epstein-barr virus drives autonomous b cell proliferation in vitro but in vivo may more subtly exploit the proliferative pathways provided by lymphoid germinal centers (gcs). murid herpesvirus 4 (muhv-4), which realistically infects inbred mice, provides a useful tool with which to understand further how a γhv colonizes b cells in vivo. not all γhvs necessarily b ... | 2014 | 24501409 |
| murine gammaherpesvirus-68 orf38 encodes a tegument protein and is packaged into virions during secondary envelopment. | tegument is the unique structure of a herpesvirion which occupies the space between nucleocapsid and envelope. accumulating data have indicated that interactions among tegument proteins play a key role in virion morphogenesis. morphogenesis of gammaherpesviruses including kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv) is poorly understood due to the lack of efficient de novo lytic replication in cell culture. murine gammaherpesvirus-68 (mhv-68) is genetically related ... | 2014 | 24474202 |
| unconventional sequence requirement for viral late gene core promoters of murine gammaherpesvirus 68. | infection with the human gammaherpesviruses, epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv), is associated with several cancers. during lytic replication of herpesviruses, viral genes are expressed in an ordered cascade. however, the mechanism by which late gene expression is regulated has not been well characterized in gammaherpesviruses. in this study, we have investigated the cis element that mediates late gene expression during de novo lytic infection with murine ... | 2014 | 24403583 |
| murine gammaherpesvirus m2 protein induction of irf4 via the nfat pathway leads to il-10 expression in b cells. | reactivation of the gammaherpesviruses epstein-barr virus (ebv), kaposi's sarcoma-associated herpesvirus (kshv) and murine gammaherpesvirus 68 (mhv68) from latently infected b cells has been linked to plasma cell differentiation. we have previously shown that the mhv68 m2 protein is important for virus reactivation from b cells and, when expressed alone in primary murine b cells, can drive b cell differentiation towards a pre-plasma cell phenotype. in addition, expression of m2 in primary murine ... | 2014 | 24391506 |
| proteomic characterization of murid herpesvirus 4 extracellular virions. | gammaherpesvirinae, such as the human epstein-barr virus (ebv) and the kaposi's sarcoma associated herpesvirus (kshv) are highly prevalent pathogens that have been associated with several neoplastic diseases. as ebv and kshv are host-range specific and replicate poorly in vitro, animal counterparts such as murid herpesvirus-4 (muhv-4) have been widely used as models. in this study, we used muhv-4 in order to improve the knowledge about proteins that compose gammaherpesviruses virions. to this en ... | 2013 | 24386290 |
| crystal structure of the gamma-2 herpesvirus lana dna binding domain identifies charged surface residues which impact viral latency. | latency-associated nuclear antigen (lana) mediates γ2-herpesvirus genome persistence and regulates transcription. we describe the crystal structure of the murine gammaherpesvirus-68 lana c-terminal domain at 2.2 å resolution. the structure reveals an alpha-beta fold that assembles as a dimer, reminiscent of epstein-barr virus ebna1. a predicted dna binding surface is present and opposite this interface is a positive electrostatic patch. targeted dna recognition substitutions eliminated dna bindi ... | 2013 | 24146618 |
| a structural basis for brd2/4-mediated host chromatin interaction and oligomer assembly of kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus lana proteins. | kaposi sarcoma-associated herpesvirus (kshv) establishes a lifelong latent infection and causes several malignancies in humans. murine herpesvirus 68 (mhv-68) is a related γ2-herpesvirus frequently used as a model to study the biology of γ-herpesviruses in vivo. the kshv latency-associated nuclear antigen (klana) and the mhv68 mlana (orf73) protein are required for latent viral replication and persistence. latent episomal kshv genomes and klana form nuclear microdomains, termed 'lana speckles', ... | 2013 | 24146614 |
| antiviral activity of angelicin against gammaherpesviruses. | human gammaherpesviruses including epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv) are important pathogens as they persist in the host and cause various malignancies. however, few antiviral drugs are available to efficiently control gammaherpesvirus replication. here we identified the antiviral activity of angelicin against murine gammaherpesvirus 68 (mhv-68), genetically and biologically related to human gammaherpesviruses. angelicin, a furocoumarin naturally occurri ... | 2013 | 23892155 |
| biological and pathogenetic characterization of different isolates of murine gammaherpesvirus 68 (mhv-68) in the context of study of human oncogenic gammaherpesviruses. | study of murine gammaherpesvirus 68 (mhv-68), which was discovered in 1980 in slovakia, has led to many important findings regarding gammaherpesviral properties in general. nowadays, it is considered to be a universal model used for detailed studies to determine pathogenetic, immunological and molecular aspects of oncogenesis in analogy to epstein-barr virus (ebv) and kaposi΄s sarcoma-associated virus (kshv). the objective of this work is to characterize biological and pathogenetic properties of ... | 2013 | 23600868 |
| illumination of murine gammaherpesvirus-68 cycle reveals a sexual transmission route from females to males in laboratory mice. | transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response. identifying their mode of transmission and their mechanisms of immune evasion is therefore essential to develop prophylactic and therapeutic strategies against these infections. as the known human gammaherpesviruses, epstein ... | 2013 | 23593002 |
| alpha beta-crystallin expression and presentation following infection with murine gammaherpesvirus 68. | alpha beta-crystallin (cryab) is a small heat shock protein that can function as a molecular chaperone and has protective effects for cells undergoing a variety of stressors. surprisingly, cryab has been identified as one of the dominant autoantigens in multiple sclerosis. it has been suggested that autoimmune mediated destruction of this small heat shock protein may limit its protective effects, thereby exacerbating inflammation and cellular damage during multiple sclerosis. it is not altogethe ... | 2013 | 23586607 |
| cd4 and cd8 t cells directly recognize murine gammaherpesvirus 68-immortalized cells and prevent tumor outgrowth. | there has been extensive research regarding t cell recognition of epstein-barr virus-transformed cells; however, less is known regarding the recognition of b cells immortalized by gamma-2 herpesviruses. here we show that b cells immortalized by murine gammaherpesvirus 68 (mhv-68, γhv-68) can be controlled by either cd4 or cd8 t cells in vivo. we present evidence for the direct recognition of infected b cells by cd4 and cd8 t cells. these data will help in the development of immunotherapeutic app ... | 2013 | 23514885 |
| an rs motif within the epstein-barr virus blrf2 tegument protein is phosphorylated by srpk2 and is important for viral replication. | epstein-barr virus (ebv) is a gammaherpesvirus that causes infectious mononucleosis, b cell lymphomas, and nasopharyngeal carcinoma. many of the genes required for ebv virion morphogenesis are found in all herpesviruses, but some are specific to gammaherpesviruses. one of these gamma-specific genes, blrf2, encodes a tegument protein that has been shown to be essential for replication in other gammaherpesviruses. in this study, we identify blrf2 interacting proteins using binary and co-complex pr ... | 2013 | 23326445 |
| modulation of b-cell tolerance by murine gammaherpesvirus 68 infection: requirement for orf73 viral gene expression and follicular helper t cells. | viruses such as epstein-barr virus (ebv) have been linked to mechanisms that support autoantibody production in diseases such as systemic lupus erythematosus. however, the mechanisms by which viruses contribute to autoantibody production remain poorly defined. this stems in part, from the high level of seropositivity for ebv (> 95%) and the exquisite species specificity of ebv. in this study we overcame these problems by using murine gammaherpesvirus 68 (mhv68), a virus genetically and biologica ... | 2013 | 23311955 |
| gammaherpesvirus latency induces antibody-associated thrombocytopenia in mice. | human herpesviruses establish lifelong latency. viral recrudescence can lead to the development of cancers, immunoproliferative disorders, transplantation complications, and thrombocytopenia. although platelet-specific autoantibodies have been reported in patients infected with the epstein-barr virus (ebv), the mechanisms by which thrombocytopenia is induced remain unclear, as do the relative contributions of lytic viral replication and latent viral gene expression. the human gammaherpesviruses ... | 2013 | 23245703 |
| herpesvirus saimiri antagonizes nuclear domain 10-instituted intrinsic immunity via an orf3-mediated selective degradation of cellular protein sp100. | in recent studies, the nuclear domain 10 (nd10) components pml, sp100, human daxx (hdaxx), and atrx were identified to be cellular restriction factors that are able to inhibit the replication of several herpesviruses. the antiviral function of nd10, however, is antagonized by viral effector proteins by a variety of strategies, including degradation of pml or relocalization of nd10 proteins. in this study, we analyzed the interplay between infection with herpesvirus saimiri (hvs), the prototypic ... | 2012 | 22278248 |
| identification of viral and host proteins that interact with murine gammaherpesvirus 68 latency-associated nuclear antigen during lytic replication: a role for hsc70 in viral replication. | latency-associated nuclear antigen (lana) is a conserved, multifunctional protein encoded by members of the rhadinovirus subfamily of gammaherpesviruses, including kaposi sarcoma-associated herpesvirus (kshv) and murine gammaherpesvirus 68 (mhv68). we previously demonstrated that mhv68 lana (mlana) is required for efficient lytic replication. however, mechanisms by which mlana facilitates viral replication, including interactions with cellular and viral proteins, are not known. thus, we performe ... | 2015 | 26581985 |
| maturation and vesicle-mediated egress of primate gammaherpesvirus rhesus monkey rhadinovirus require inner tegument protein orf52. | the tegument layer of herpesviruses comprises a collection of proteins that is unique to each viral species. in rhesus monkey rhadinovirus (rrv), a close relative of the human oncogenic pathogen kaposi's sarcoma-associated herpesvirus, orf52 is a highly abundant tegument protein tightly associated with the capsid. we now report that orf52 knockdown during rrv infection of rhesus fibroblasts led to a greater than 300-fold reduction in the viral titer by 48 h but had little effect on the number of ... | 2014 | 24899183 |
| a tissue culture model of murine gammaherpesvirus replication reveals roles for the viral cyclin in both virus replication and egress from infected cells. | passage through the eukaryotic cell cycle is regulated by the activity of cyclins and their cyclin-dependent kinase partners. rhadinoviruses, such as kaposi's sarcoma-associated herpesvirus (kshv) and murine gammaherpesvirus 68 (mhv68), encode a viral homologue of mammalian d-type cyclins. in mhv68, the interaction of the viral cyclin with its cdk partners is important for acute replication in the lungs following low dose inoculation. attempts to further study this requirement in vitro have been ... | 2014 | 24695529 |
| unbiased mutagenesis of mhv68 lana reveals a dna-binding domain required for lana function in vitro and in vivo. | the latency-associated nuclear antigen (lana), encoded by orf73, is a conserved gene among the γ2-herpesviruses (rhadinoviruses). the kaposi's sarcoma-associated herpesvirus (kshv) lana is consistently expressed in kshv-associated malignancies. in the case of the rodent γ2-herpesvirus, murine gammaherpesvirus 68 (mhv68), the lana homolog (mlana) is required for efficient virus replication, reactivation from latency and immortalization of murine fetal liver-derived b cells. to gain insights into ... | 2012 | 22969427 |
| vaccine prospect of kaposi sarcoma-associated herpesvirus. | infection of kaposi sarcoma-associated herpesvirus (kshv) or human herpesvirus-8 (hhv-8) is estimated to account for 34,000 new cancer cases globally. unlike other herpesviruses, kshv is not ubiquitous but is highly prevalent in some areas, such as sub-saharan africa where kaposi sarcoma is the leading cancer among adults. while latent infection of kshv plays a major and direct role in tumorigenesis, viral lytic replication also makes significant contributions to this process. efforts to develop ... | 2012 | 22795202 |
| murine gammaherpesvirus 68 orf75c contains ubiquitin e3 ligase activity and requires pml sumoylation but not other known cellular pml regulators, ck2 and e6ap, to mediate pml degradation. | all gammaherpsviruses encode at least one gene related to the cellular formylglycinamide ribonucleotide amidotransferase (fgarat) enzyme but their biological roles are relatively unknown. the murine gammaherpesvirus 68 (mhv68) vfgarat, orf75c, mediates a proteasome-dependent degradation of the antiviral promyelocytic leukemia (pml) protein by an unknown mechanism, which is addressed in this study. we found that orf75c interacts weakly with pml and sumo-modified forms of pml are important for its ... | 2013 | 23541081 |
| the influence of dual infection with herpes and influenza viruses on the differential blood cell count of mice. | based on our previous results, which confirmed the role of latent gammaherpesvirus infection in alteration of immune homeostasis, we studied the influence of simultaneous infection with gammaherpes and influenza viruses on selected parameters of innate immunity, particularly on the subpopulations of peripheral blood cell leukocytes. the aim was to analyze changes of differential blood cell count of balb/c mice persistently infected with murine gammaherpesvirus 68 (mhv-68) and subsequently co-inf ... | 2017 | 27928917 |
| mhv68 latency modulates the host immune response to influenza a virus. | murine gammaherpesvirus 68 (mhv68) is a natural rodent pathogen that has been used as a model to study the pathogenesis of human gammaherpesviruses. like other herpesviruses, mhv68 causes acute infection and establishes life-long latency in the host. recently, it has been shown that mice latently infected with mhv68 have resistance to unrelated pathogens in secondary infection models. we therefore hypothesized that latent mhv68 infection could modulate the host response to influenza a virus. to ... | 2013 | 23807051 |
| the viral bcl-2 homologs of kaposi's sarcoma-associated herpesvirus and rhesus rhadinovirus share an essential role for viral replication. | ks-bcl-2 is a kaposi's sarcoma-associated herpesvirus (kshv)-encoded viral bcl-2 (vbcl-2) homolog which has apoptosis- and autophagy-inhibiting activity when expressed in transfected cells. however, little is known about its function during viral infection. as ks-bcl-2 is expressed during the lytic replication cycle, we used constitutively lytic and inducibly lytic kshv mutants to investigate the role of ks-bcl-2 during the lytic cycle. we show that kshv cannot complete the lytic replication cyc ... | 2017 | 28053098 |
| in vivo examination of mouse apobec3- and human apobec3a- and apobec3g-mediated restriction of parvovirus and herpesvirus infection in mouse models. | apobec3 knockout and human apobec3a and -3g transgenic mice were tested for their ability to be infected by the herpesviruses herpes simplex virus 1 and murine herpesvirus 68 and the parvovirus minute virus of mice (mvm). knockout, apobec3a and apobec3g transgenic, and wild-type mice were equally infected by the herpesviruses, while apobec3a but not mouse apobec3 conferred resistance to mvm. no viruses showed evidence of cytidine deamination by mouse or human apobec3s. these data suggest that in ... | 2016 | 27356895 |
| induction of necroptotic cell death by viral activation of the rig-i or sting pathway. | necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase rip1 and its family member rip3. necroptosis occurs when rip1 is deubiquitinated to form a complex with rip3 in cells deficient in the death receptor adapter molecule fadd or caspase-8. necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. to see how general ... | 2017 | 28060376 |
| type i interferons direct gammaherpesvirus host colonization. | gamma-herpesviruses colonise lymphocytes. murid herpesvirus-4 (muhv-4) infects b cells via epithelial to myeloid to lymphoid transfer. this indirect route entails exposure to host defences, and type i interferons (ifn-i) limit infection while viral evasion promotes it. to understand how ifn-i and its evasion both control infection outcomes, we used mx1-cre mice to tag floxed viral genomes in ifn-i responding cells. epithelial-derived muhv-4 showed low ifn-i exposure, and neither disrupting viral ... | 2016 | 27223694 |
| enzymatically enhanced collisions on ultramicroelectrodes for specific and rapid detection of individual viruses. | we report the specific collision of a single murine cytomegalovirus (mcmv) on a platinum ultramicroelectrode (ume, radius of 1 μm). antibody directed against the viral surface protein glycoprotein b functionalized with glucose oxidase (gox) allowed for specific detection of the virus in solution and a biological sample (urine). the oxidation of ferrocene methanol to ferrocenium methanol was carried out at the electrode surface, and the ferrocenium methanol acted as the cosubstrate to gox to cata ... | 2016 | 27217569 |
| pervasive transcription of a herpesvirus genome generates functionally important rnas. | pervasive transcription is observed in a wide range of organisms, including humans, mice, and viruses, but the functional significance of the resulting transcripts remains uncertain. current genetic approaches are often limited by their emphasis on protein-coding open reading frames (orfs). we previously identified extensive pervasive transcription from the murine gammaherpesvirus 68 (mhv68) genome outside known orfs and antisense to known genes (termed expressed genomic regions [egrs]). similar ... | 2014 | 24618256 |
| comparative study of two models of combined pulmonary fibrosis and emphysema in mice. | combined pulmonary fibrosis and emphysema (cpfe) is an "umbrella term" encompassing emphysema and pulmonary fibrosis, but its pathogenesis is not known. we established two models of cpfe in mice using tracheal instillation with bleomycin (blm) or murine gammaherpesvirus 68 (mhv-68). experimental mice were divided randomly into four groups: a (normal control, n=6), b (emphysema, n=6), c (emphysema+mhv-68, n=24), d (emphysema+blm, n=6). group c was subdivided into four groups: c1 (sacrificed on da ... | 2017 | 28233574 |
| rta occupancy of the origin of lytic replication during murine gammaherpesvirus 68 reactivation from b cell latency. | rta, the viral replication and transcription activator, is essential for rhadinovirus lytic gene expression upon de novo infection and reactivation from latency. lipopolysaccharide (lps)/toll-like receptor (tlr)4 engagement enhances rhadinovirus reactivation. we developed two new systems to examine the interaction of rta with host nf-kappab (nf-κb) signaling during murine gammaherpesvirus 68 (mhv68) infection: a latent b cell line (he-rit) inducible for rta-flag expression and virus reactivation ... | 2017 | 28212352 |
| the effect of isoprinosine treatment on persistent infection of balb/c mice infected with murine gammaherpesvirus 68. | we demonstrated the positive effect of isoprinosine treatment on persistent infection of balb/c mice with murine gammaherpesvirus 68 (mhv-68). increased number of leukocytes, increased percentage of neutrophils, elevated levels of virus-neutralizing (vn) antibodies, reduced number of atypical lymphocytes and reduced virus titers were detected in the examined organs after a 14-day treatment. the positive effect of isoprinosine therapy vanished after 120-150 days. after this interval, we demonstra ... | 2017 | 28105852 |
| transforming activity of murine herpesvirus 68 putative growth factor is related to the ability to change cytoskeletal structure. | murine herpesvirus 68 (mhv-68) can transform cells in vitro and in vivo. we investigated putative murine herpesvirus growth factors (mhgfs) obtained by the separation of cell-free media from mhv-68-transformed cells on an fplc sephadex g15 column. the transforming activity of the mhgfa fraction was related to depolymerization of actin, disruption of the microtubule network, and punctate-reticular changes of the golgi. the mhgfw fraction had only repressing activity on the transformed phenotype. ... | 2016 | 28052265 |
| molecular detection of murine gammaherpesvirus 68 (mhv-68) in haemaphysalis concinna ticks collected in slovakia. | murine gammaherpesvirus 68 (mhv-68) is a natural pathogen of murid rodents, which serve as hosts to haemaphysalis concinna ticks. the occurrence of mhv-68 was investigated in a total of 47 h. concinna adult ticks collected on the vegetation in gabčíkovo, situated in south-western slovakia (47º54´0´´n, 17º35´0´´e), from may 2013 to may 2014. dna from ticks was purified and screened by nested pcr targeting orf50 of mhv-68 and the copy number of virus genome in ticks was determined by a real-time p ... | 2017 | 27928925 |
| type i interferons and nk cells restrict gammaherpesvirus lymph node infection. | gammaherpesviruses establish persistent, systemic infections and cause cancers. murid herpesvirus 4 (muhv-4) provides a unique window into the early events of host colonization. it spreads via lymph nodes. while dendritic cells (dc) pass muhv-4 to lymph node b cells, subcapsular sinus macrophages (ssm), which capture virions from the afferent lymph, restrict its spread. understanding how this restriction works offers potential clues to a more comprehensive defense. type i interferon (ifn-i) bloc ... | 2016 | 27466430 |
| tegument protein orf45 plays an essential role in virion morphogenesis of 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, ... | 2016 | 27226376 |
| multiple lytic origins of replication are required for optimal gammaherpesvirus fitness in vitro and in vivo. | an unresolved question in herpesvirus biology is why some herpesviruses contain more than one lytic origin of replication (orilyt). using murine gammaherpesvirus 68 (mhv-68) as model virus containing two orilyts, we demonstrate that loss of either of the two orilyts was well tolerated in some situations but not in others both in vitro and in vivo. this was related to the cell type, the organ or the route of inoculation. depending on the cell type, different cellular proteins, for example hexim1 ... | 2016 | 27007137 |
| sequence variability among murine herpesvirus isolates shows possible effect of long-term in vitro passaging on their genome. | no abstract keywords: murine herpesvirus 68; virus isolates; sequence analysis; restriction fragment length polymorphism. | 2016 | 26982476 |
| prevention of tumor formation by latent gammaherpesvirus infection. | recent reports suggested that chronic herpesvirus infection, as a constituent of the so-called virome, may not only exert harmful effects but may also be beneficial to the host, for example mediating increased resistance to secondary infections or to tumors. to further challenge this concept, specifically regarding increased resistance to tumors, we infected chimeric hla-dr4-h2-e (dr4) mice, a mouse strain which spontaneously develops hematological tumors, with the rodent herpesvirus murine gamm ... | 2015 | 26714031 |
| murine gammaherpesvirus 68 lana and sox homologs counteract atm-driven p53 activity during lytic viral replication. | tumor suppressor p53 is activated in response to numerous cellular stresses, including viral infection. however, whether murine gammaherpesvirus 68 (mhv68) provokes p53 during the lytic replication cycle has not been extensively evaluated. here, we demonstrate that mhv68 lytic infection induces p53 phosphorylation and stabilization in a manner that is dependent on the dna damage response (ddr) kinase ataxia telangiectasia mutated (atm). the induction of p53 during mhv68 infection occurred in mul ... | 2015 | 26676792 |
| deletion of murid herpesvirus 4 orf63 affects the trafficking of incoming capsids toward the nucleus. | gammaherpesviruses are important human and animal pathogens. despite the fact that they display the classical architecture of herpesviruses, the function of most of their structural proteins is still poorly defined. this is especially true for tegument proteins. interestingly, a potential role in immune evasion has recently been proposed for the tegument protein encoded by kaposi's sarcoma-associated herpesvirus open reading frame 63 (orf63). to gain insight about the roles of orf63 in the life ... | 2015 | 26676769 |
| cells transformed by murine herpesvirus 68 (mhv-68) release compounds with transforming and transformed phenotype suppressing activity resembling growth factors. | in this study, we investigated the medium of three cell lines transformed with murine herpesvirus 68 (mhv-68) in vitro and in vivo, 68/hdf, 68/nih3t3, and s11e, for the presence of compounds resembling growth factors of some herpesviruses which have displayed transforming and transformed phenotype suppressing activity in normal and tumor cells. when any of spent medium was added to cell culture we observed the onset of transformed phenotype in baby hamster kidney cells (bhk-21) cells and transfo ... | 2015 | 26666191 |
| epigenetic modification of rta (orf50) promoter is not responsible for distinct reactivation patterns of murine gammaherpesviruses. | gammaherpesviruses-encoded replication and transcription activator (rta) (orf50) plays an essential role in the initiation of viral lytic gene expression and reactivation from latency. the rta expression is influenced by many viral and cellular factors, including epigenetic modifications, mainly dna methylation and histone modifications. murine gammaherpesvirus 68 (mhv-68), belonging to the species murid herpesvirus (muhv-4), is widely used as a model to study human gammaherpesvirus infections i ... | 2015 | 26666189 |
| infection-induced retrotransposon-derived noncoding rnas enhance herpesviral gene expression via the nf-κb pathway. | short interspersed nuclear elements (sines) are highly abundant, rna polymerase iii-transcribed noncoding retrotransposons that are silenced in somatic cells but activated during certain stresses including viral infection. how these induced sine rnas impact the host-pathogen interaction is unknown. here we reveal that during murine gammaherpesvirus 68 (mhv68) infection, rapidly induced sine rnas activate the antiviral nf-κb signaling pathway through both mitochondrial antiviral-signaling protein ... | 2015 | 26584434 |
| murid gammaherpesvirus latency-associated protein m2 promotes the formation of conjugates between transformed b lymphoma cells and t helper cells. | establishment of persistent infection in memory b cells by murid herpesvirus-4 (muhv-4) depends on the proliferation of latently infected germinal center b cells, for which t cell help is essential. whether the virus is capable of modulating b-t helper cell interaction for its own benefit is still unknown. here, we investigate if the muhv-4 latency associated m2 protein, which assembles multiprotein complexes with b cell signaling proteins, plays a role. we observed that m2 led to the upregulati ... | 2015 | 26544979 |
| downregulation of poly(adp-ribose) polymerase 1 by a viral processivity factor facilitates lytic replication of gammaherpesvirus. | in kaposi's sarcoma-associated herpesvirus (kshv), poly(adp-ribose) polymerase 1 (parp-1) acts as an inhibitor of lytic replication. here, we demonstrate that kshv downregulated parp-1 upon reactivation. the viral processivity factor of kshv (pf-8) interacted with parp-1 and was sufficient to degrade parp-1 in a proteasome-dependent manner; this effect was conserved in murine gammaherpesvirus 68. pf-8 knockdown in kshv-infected cells resulted in reduced lytic replication upon reactivation with i ... | 2015 | 26157130 |
| copper(ii) complexes with new fluoroquinolones: synthesis, structure, spectroscopic and theoretical study, dna damage, cytotoxicity and antiviral activity. | copper(ii) complexes with fluoroquinolones in the presence of the nitrogen donor heterocyclic ligands 1,10-phenanthroline have been considered in detail. the phenanthroline moiety was introduced into the ligand environment with the aim to determine whether the nuclease activity is feasible. all suitable x-ray structures of the complexes under study reveal a distorted square pyramidal coordination geometry for cu(ii) atom. the conformational and spectroscopic (ft-ir and uv-visible) behavior has b ... | 2015 | 26116423 |
| b-cell-independent lymphoid tissue infection by a b-cell-tropic rhadinovirus. | lymphocytes provide gammaherpesviruses with a self-renewing substrate for persistent infection and with transport to mucosal sites for host exit. their role in the initial colonization of new hosts is less clear. murid herpesvirus 4 (muhv-4), an experimentally accessible, b-cell-tropic rhadinovirus (gamma-2 herpesvirus), persistently infects both immunocompetent and b-cell-deficient mice. a lack of b-cells did not compromise muhv-4 entry into lymphoid tissue, which involved myeloid cell infectio ... | 2015 | 25986632 |
| detection of murine herpesvirus 68 (mhv-68) in dermacentor reticulatus ticks. | murid herpesvirus 4 (muhv 4) strain 68 (mhv-68) is a natural pathogen of murid rodents, which serves as hosts to dermacentor reticulatus ticks. these ticks are known to transmit multiple pathogens, which can cause diseases in humans and animals. recently, the detection of mhv-68 antibodies in the blood of animals living in the same biotope as virus-infected mice has suggested the role of ticks in pathogen circulation in nature. herein, to identify mhv-68 in d. reticulatus ticks, dna samples from ... | 2015 | 25947097 |
| interleukin 21 signaling in b cells is required for efficient establishment of murine gammaherpesvirus latency. | the human gammaherpesviruses take advantage of normal b cell differentiation pathways to establish life-long infection in memory b cells. murine gammaherpesvirus 68 (mhv68) infection of laboratory strains of mice also leads to life-long infection in memory b cells. to gain access to the memory b cell population, mhv68 infected b cells pass through the germinal center reaction during the onset of latency and require signals from t follicular helper (tfh) cells for proliferation. interleukin 21 (i ... | 2015 | 25875847 |
| murine gammaherpesvirus 68 pathogenesis is independent of caspase-1 and caspase-11 in mice and impairs interleukin-1β production upon extrinsic stimulation in culture. | gammaherpesviruses establish lifelong infections that are associated with the development of cancer. these viruses subvert many aspects of the innate and adaptive immune response of the host. the inflammasome, a macromolecular protein complex that controls inflammatory responses to intracellular danger signals generated by pathogens, is both activated and subverted during human gammaherpesvirus infection in culture. the impact of the inflammasome response on gammaherpesvirus replication and late ... | 2015 | 25855746 |
| rhadinovirus host entry by co-operative infection. | rhadinoviruses establish chronic infections of clinical and economic importance. several show respiratory transmission and cause lung pathologies. we used murid herpesvirus-4 (muhv-4) to understand how rhadinovirus lung infection might work. a primary epithelial or b cell infection often is assumed. muhv-4 targeted instead alveolar macrophages, and their depletion reduced markedly host entry. while host entry was efficient, alveolar macrophages lacked heparan - an important rhadinovirus binding ... | 2015 | 25790477 |
| possible role of different animal species in maintenance and spread of murine gammaherpesvirus 68 in the nature. | murine gammaherpesvirus 68 (mhv-68), isolated from a bank vole (clethrionomys glareolus) in slovakia in 1976 is a natural pathogen of wild murid rodents. this review is focused to biological properties of this pathogen, the mode of its maintenance in murid rodents as reservoir animals, mechanisms of its spread to other animals in the same biotope as well as to livestock and household animals. potential role of ticks as vectors and the possibility of infection of humans with this virus are consid ... | 2015 | 25790046 |
| murine gammaherpesvirus 68 orf48 is an rta-responsive gene product and functions in both viral lytic replication and latency during in vivo infection. | replication and transcription activator (rta) of gammaherpesvirus is an immediate early gene product and regulates the expression of many downstream viral lytic genes. orf48 is also conserved among gammaherpesviruses; however, its expression regulation and function remained largely unknown. in this study, we characterized the transcription unit of orf48 from murine gammaherpesvirus 68 (mhv-68) and analyzed its transcriptional regulation. we showed that rta activates the orf48 promoter via an rta ... | 2015 | 25762743 |
| murine gammaherpesvirus (mhv-68) transforms cultured cells in vitro. | human dermal fibroblasts and mouse nih/3t3 cells acquired the transformed phenotype ('criss-cross' pattern of growth) after infection with ultraviolet-irradiated murine gammaherpesvirus (muhv-4 strain 68; mhv-68). these cells with changed phenotype could be serially cultured for 5-6 passages (35-40 days), and then they entered into crisis and most of them died. in a small number of cultures, however, foci of newly transformed cells appeared from which two stable cell lines were derived. after 6- ... | 2015 | 25677084 |
| evasion of innate cytosolic dna sensing by a gammaherpesvirus facilitates establishment of latent infection. | herpesviruses are dna viruses harboring the capacity to establish lifelong latent-recurrent infections. there is limited knowledge about viruses targeting the innate dna-sensing pathway, as well as how the innate system impacts on the latent reservoir of herpesvirus infections. in this article, we report that murine gammaherpesvirus 68 (mhv68), in contrast to α- and β-herpesviruses, induces very limited innate immune responses through dna-stimulated pathways, which correspondingly played only a ... | 2015 | 25595793 |
| mesenchymal stem cells detect and defend against gammaherpesvirus infection via the cgas-sting pathway. | mesenchymal stem cells (mscs) are widely used in clinical settings to treat tissue injuries and autoimmune disorders due to their multipotentiality and immunomodulation. long-term observations reveal several complications after mscs infusion, especially herpesviral infection. however, the mechanism of host defense against herpesviruses in mscs remains largely unknown. here we showed that murine gammaherpesvirus-68 (mhv-68), which is genetically and biologically related to human gammaherpesviruse ... | 2015 | 25592282 |
| absence of the uracil dna glycosylase of murine gammaherpesvirus 68 impairs replication and delays the establishment of latency in vivo. | uracil dna glycosylases (ung) are highly conserved proteins that preserve dna fidelity by catalyzing the removal of mutagenic uracils. all herpesviruses encode a viral ung (vung), and yet the role of the vung in a pathogenic course of gammaherpesvirus infection is not known. first, we demonstrated that the vung of murine gammaherpesvirus 68 (mhv68) retains the enzymatic function of host ung in an in vitro class switch recombination assay. next, we generated a recombinant mhv68 with a stop codon ... | 2015 | 25589640 |
| establishment of murine gammaherpesvirus latency in b cells is not a stochastic event. | murid γ-herpesvirus-4 (muhv-4) promotes polyclonal b cell activation and establishes latency in memory b cells via unclear mechanisms. we aimed at exploring whether b cell receptor specificity plays a role in b cell susceptibility to viral latency and how this is related to b cell activation. we first observed that muhv-4-specific b cells represent a minority of the latent population, and to better understand the influence of the virus on non-muhv-4 specific b cells we used the swhel mouse model ... | 2014 | 25079788 |
| to the editor: murine gammaherpesvirus 68 (mhv-68) escapes from nk-cell-mediated immune surveillance by a ceacam1-mediated immune evasion mechanism. | | 2014 | 24976512 |
| defining immune engagement thresholds for in vivo control of virus-driven lymphoproliferation. | persistent infections are subject to constant surveillance by cd8+ cytotoxic t cells (ctl). their control should therefore depend on mhc class i-restricted epitope presentation. many epitopes are described for γ-herpesviruses and form a basis for prospective immunotherapies and vaccines. however the quantitative requirements of in vivo immune control for epitope presentation and recognition remain poorly defined. we used murid herpesvirus-4 (muhv-4) to determine for a latently expressed viral ep ... | 2014 | 24967892 |
| activation of nf-κb via endosomal toll-like receptor 7 (tlr7) or tlr9 suppresses murine herpesvirus 68 reactivation. | in order to understand and possibly treat b-cell malignancies associated with latent gammaherpesvirus infection, it is vital to understand the factors that control the balance between the two transcriptional states of gammaherpesviruses: latency and lytic replication. we used murine gammaherpesvirus 68 (mhv 68) as a model system to investigate how engagement of endosomal toll-like receptors (tlrs) impacts reactivation from latency in vitro and establishment of latent infection in vivo. we found ... | 2014 | 24942583 |
| the gammaherpesviruses kaposi's sarcoma-associated herpesvirus and murine gammaherpesvirus 68 modulate the toll-like receptor-induced proinflammatory cytokine response. | the human pathogen kaposi's sarcoma-associated herpesvirus (kshv), the etiological agent of kaposi's sarcoma, primary effusion lymphoma, and multicentric castleman's disease, establishes lifelong latency upon infection. murine gammaherpesvirus 68 (mhv68) is a well-established model for kshv. toll-like receptors (tlrs) play a crucial role for the innate immune response to pathogens. although kshv and mhv68 are detected by tlrs, studies suggest they modulate tlr4 and tlr9 signaling, respectively. ... | 2014 | 24899179 |
| promotion of a subdominant cd8 t cell response during murine gammaherpesvirus 68 infection in the absence of cd4 t cell help. | cd8 and cd4 t cells are each critically important for immune control of murine gammaherpesvirus 68 (γhv68) infection. in immunocompetent mice, acute γhv68 infection results in lifelong latency, but in the absence of cd4 t cell help, mice succumb to viral recrudescence and disease. however, the requirements for cd4 t cell help in the generation and maintenance of antiviral cd8 t cell responses are incompletely understood, and it is unclear whether there are epitope-specific differences in the req ... | 2014 | 24789784 |
| a conserved rna polymerase iii promoter required for gammaherpesvirus tmer transcription and microrna processing. | canonical rna polymerase iii (pol iii) type 2 promoters contain a single a and b box and are well documented for their role in trna and sine transcription in eukaryotic cells. the genome of murid herpesvirus 4 (muhv-4) contains eight polycistronic trna-microrna encoded rna (tmer) genes that are transcribed from a rna pol iii type 2-like promoter containing triplicated a box elements. here, we demonstrate that the triplicated a box sequences are required in their entirety to produce functional mu ... | 2014 | 24747015 |
| host restriction of murine gammaherpesvirus 68 replication by human apobec3 cytidine deaminases but not murine apobec3. | humans encode seven apobec3 (a3a-a3h) cytidine deaminase proteins that differ in their expression profiles, preferred nucleotide recognition sequence and capacity for restriction of rna and dna viruses. we identified apobec3 hotspots in numerous herpesvirus genomes. to determine the impact of host apobec3 on herpesvirus biology in vivo, we examined whether murine apobec3 (ma3) restricts murine gammaherpesvirus 68 (mhv68). viral replication was impaired by several human apobec3 proteins, but not ... | 2014 | 24725948 |
| a murid gamma-herpesviruses exploits normal splenic immune communication routes for systemic spread. | gamma-herpesviruses (γhvs) are widespread oncogenic pathogens that chronically infect circulating lymphocytes. how they subvert the immune check-point function of the spleen to promote persistent infection is not clear. we show that murid herpesvirus-4 (muhv-4) enters the spleen by infecting marginal zone (mz) macrophages, which provided a conduit to mz b cells. relocation of mz b cells to the white pulp allowed virus transfer to follicular dendritic cells. from here the virus reached germinal c ... | 2014 | 24721574 |
| murine gammaherpesvirus 68 encoding open reading frame 11 targets tank binding kinase 1 to negatively regulate the host type i interferon response. | upon viral infection, type i interferons, such as alpha and beta interferon (ifn-α and ifn-β, respectively), are rapidly induced and activate multiple antiviral genes, thereby serving as the first line of host defense. many dna and rna viruses counteract the host interferon system by modulating the production of ifns. in this study, we report that murine gammaherpesvirus 68 (mhv-68), a double-stranded dna virus, encodes open reading frame 11 (orf11), a novel immune modulator, to block ifn-β prod ... | 2014 | 24696485 |
| ifnγ and perforin cooperate to control infection and prevent fatal pathology during persistent gammaherpesvirus infection in mice. | infection with murine gammaherpesvirus 68 has become an accepted model for studying the virus/host interactions with regard to gammaherpesvirus infections. previous studies using gene-deficient mice have revealed that neither ifnγ nor perforin is essential in controlling the outcome of infection or the virus load during chronic infection in c57bl/6 mice. however, pronounced multiorgan fibrosis and splenic atrophy are observed in mice lacking ifnγ or the ifnγ receptor. to study the interplay betw ... | 2014 | 24684620 |
| enhanced response of t cells from murine gammaherpesvirus 68-infected mice lacking the suppressor of t cell receptor signaling molecules sts-1 and sts-2. | the human gammaherpesviruses establish life-long infections that are associated with the development of lymphomas and neoplasms, especially in immunocompromised individuals. t cells play a crucial role in the control of gammaherpesvirus infection through multiple functions, including the direct killing of infected cells, production of cytokines such as interferon-γ (ifn-γ), and costimulation of b cells. impaired t cell function in mice infected with murine gammaherpesvirus 68 (mhv68) leads to in ... | 2014 | 24587276 |
| identification of alternative transcripts encoding the essential murine gammaherpesvirus lytic transactivator rta. | the essential immediate early transcriptional activator rta, encoded by gene 50, is conserved among all characterized gammaherpesviruses. analyses of a recombinant murine gammaherpesvirus 68 (mhv68) lacking both of the known gene 50 promoters (g50dblko) revealed that this mutant retained the ability to replicate in the simian kidney epithelial cell line vero but not in permissive murine fibroblasts following low-multiplicity infection. however, g50dblko replication in permissive fibroblasts was ... | 2014 | 24574412 |
| virtual screening of m3 protein antagonists for finding a model to study the gammaherpesvirus damaged immune system and chemokine related diseases. | m3 protein is a chemokine decoy receptor involved in pathogenesis of persistent infection with gammaherpesvirus and complications related to the latency of this pathogen. we proposed that antagonists of the m3 would provide a unique opportunity for studying new therapeutic strategies in disordered immune system, immune-deficient states and role of chemokines in pathogenesis development. | 2013 | 24455481 |
| murine gammaherpesvirus 68 encodes a second pml-modifying protein. | the orf75c tegument protein of murine gammaherpesvirus 68 (mhv68) promotes the degradation of the antiviral promyelocytic leukemia (pml) protein. surprisingly, mhv68 expressing a degradation-deficient orf75c replicated in cell culture and in mice similar to the wild-type virus. however, in cells infected with this mutant virus, pml formed novel track-like structures that are induced by orf61, the viral ribonucleotide reductase large subunit. these findings may explain why orf75c mutant viruses u ... | 2014 | 24371073 |
| rodent herpesvirus peru encodes a secreted chemokine decoy receptor. | viruses have long been studied not only for their pathology and associated disease but also as model systems for understanding cellular and immunological processes. rodent herpesvirus peru (rhvp) is a recently characterized rhadinovirus related to murine gammaherpesvirus 68 (mhv68) and kaposi's sarcoma-associated herpesvirus (kshv) that establishes acute and latent infection in laboratory mice. rhvp encodes numerous unique proteins that we hypothesize might facilitate host immune evasion during ... | 2014 | 24173234 |
| phosphoproteomic analyses reveal signaling pathways that facilitate lytic gammaherpesvirus replication. | lytic gammaherpesvirus (ghv) replication facilitates the establishment of lifelong latent infection, which places the infected host at risk for numerous cancers. as obligate intracellular parasites, ghvs must control and usurp cellular signaling pathways in order to successfully replicate, disseminate to stable latency reservoirs in the host, and prevent immune-mediated clearance. to facilitate a systems-level understanding of phosphorylation-dependent signaling events directed by ghvs during ly ... | 2013 | 24068923 |
| promyelocytic leukemia protein modulates establishment and maintenance of latent gammaherpesvirus infection in peritoneal cells. | promyelocytic leukemia protein (pml) is an essential organizer of pml nuclear bodies (nbs), which carry out a variety of activities, including antiviral functions. herpesviruses from all subfamilies encode proteins that counteract pml nb-mediated antiviral defenses by multiple mechanisms. however, because of the species specificity of herpesviruses, only a limited number of in vivo studies have been undertaken to investigate the effect of pml or pml nbs on herpesvirus infection. to address this ... | 2013 | 23986598 |
| glycoprotein b cleavage is important for murid herpesvirus 4 to infect myeloid cells. | glycoprotein b (gb) is a conserved herpesvirus virion component implicated in membrane fusion. as with many-but not all-herpesviruses, the gb of murid herpesvirus 4 (muhv-4) is cleaved into disulfide-linked subunits, apparently by furin. preventing gb cleavage for some herpesviruses causes minor infection deficits in vitro, but what the cleavage contributes to host colonization has been unclear. to address this, we mutated the furin cleavage site (r-r-k-r) of the muhv-4 gb. abolishing gb cleavag ... | 2013 | 23903840 |
| myxomavirus-derived serpin prolongs survival and reduces inflammation and hemorrhage in an unrelated lethal mouse viral infection. | lethal viral infections produce widespread inflammation with vascular leak, clotting, and bleeding (disseminated intravascular coagulation [dic]), organ failure, and high mortality. serine proteases in clot-forming (thrombotic) and clot-dissolving (thrombolytic) cascades are activated by an inflammatory cytokine storm and also can induce systemic inflammation with loss of normal serine protease inhibitor (serpin) regulation. myxomavirus secretes a potent anti-inflammatory serpin, serp-1, that in ... | 2013 | 23774438 |
| systemic and local infection routes govern different cellular dissemination pathways during gammaherpesvirus infection in vivo. | human gammaherpesviruses cause morbidity and mortality associated with infection and transformation of lymphoid and endothelial cells. knowledge of cell types involved in virus dissemination from primary virus entry to virus latency is fundamental for the understanding of gammaherpesvirus pathogenesis. however, the inability to directly trace cell types with respect to virus dissemination pathways has prevented definitive conclusions regarding the relative contribution of individual cell types. ... | 2013 | 23408606 |
| the absence of m1 leads to increased establishment of murine gammaherpesvirus 68 latency in igd-negative b cells. | the secreted m1 protein of murine gammaherpesvirus 68 (mhv68) promotes effector vβ4(+) cd8(+) t cell expansion to impact virus control and immune-mediated pathologies in c57bl/6 mice, but not balb/c mice. we report a striking increase in the number of genome-positive, igd(-) b cells during chronic infection of both mouse strains. this suggests a novel role for m1 in influencing long-term maintenance in a major latency reservoir irrespective of the degree of vβ4(+) cd8(+) t cell expansion. | 2013 | 23302876 |
| role of src homology domain binding in signaling complexes assembled by the murid γ-herpesvirus m2 protein. | γ-herpesviruses express proteins that modulate b lymphocyte signaling to achieve persistent latent infections. one such protein is the m2 latency-associated protein encoded by the murid herpesvirus-4. m2 has two closely spaced tyrosine residues, tyr(120) and tyr(129), which are phosphorylated by src family tyrosine kinases. here we used mass spectrometry to identify the binding partners of tyrosine-phosphorylated m2. each m2 phosphomotif is shown to bind directly and selectively to sh2-containin ... | 2013 | 23258536 |
| a heparan-dependent herpesvirus targets the olfactory neuroepithelium for host entry. | herpesviruses are ubiquitous pathogens that cause much disease. the difficulty of clearing their established infections makes host entry an important target for control. however, while herpesviruses have been studied extensively in vitro, how they cross differentiated mucus-covered epithelia in vivo is unclear. to establish general principles we tracked host entry by murid herpesvirus-4 (muhv-4), a lymphotropic rhadinovirus related to the kaposi's sarcoma-associated herpesvirus. spontaneously ac ... | 2012 | 23133384 |
| noncanonical micrornas and endogenous sirnas in lytic infection of murine gammaherpesvirus. | microrna (mirna) and endogenous small interfering rna (endo-sirna) are two essential classes of small noncoding rnas (sncrnas) in eukaryotes. the class of mirna is diverse and there exist noncanonical mirnas that bypass the canonical mirna biogenesis pathway. in order to identify noncanonical mirnas and endo-sirnas responding to virus infection and study their potential function, we sequenced small-rna species from cells lytically infected with murine gammaherpesvirus 68 (mhv68). in addition to ... | 2012 | 23110115 |
| partial genome analysis of murine gammaherpesvirus 4556. | murine gammaherpesvirus 68 (mhv-68) -infected mouse is an animal model of gammaherpesvirus infection in man and domestic animals. murine gammaherpesvirus 4556 (mhv-4556), isolated from apodemus flavicollis ticks has been considered a close relative of mhv-68 but different in some features of infection in vitro and in vivo. previous comparison of mhv-4556 with mhv-68 has revealed their diversity in immune evasion protein mk3. in this study, hindiii and ecori restriction profiles of the mhv-4556 g ... | 2012 | 23043597 |
| myeloid infection links epithelial and b cell tropisms of murid herpesvirus-4. | gamma-herpesviruses persist in lymphocytes and cause disease by driving their proliferation. lymphocyte infection is therefore a key pathogenetic event. murid herpesvirus-4 (muhv-4) is a rhadinovirus that like the related kaposi's sarcoma-associated herpesvirus persists in b cells in vivo yet infects them poorly in vitro. here we used muhv-4 to understand how virion tropism sets the path to lymphocyte colonization. virions that were highly infectious in vivo showed a severe post-binding block to ... | 2012 | 23028329 |
| amplification of jnk signaling is necessary to complete the murine gammaherpesvirus 68 lytic replication cycle. | several studies have previously defined host-derived signaling events capable of driving lytic gammaherpesvirus replication or enhancing immediate-early viral gene expression. yet signaling pathways that regulate later stages of the productive gammaherpesvirus replication cycle are still poorly defined. in this study, we utilized a mass spectrometric approach to identify c-jun as an abundant cellular phosphoprotein present in late stages of lytic murine gammaherpesvirus 68 (mhv68) infection. kin ... | 2012 | 23015701 |
| characterization of omental immune aggregates during establishment of a latent gammaherpesvirus infection. | herpesviruses are characterized by their ability to establish lifelong latent infection. the gammaherpesvirus subfamily is distinguished by lymphotropism, establishing and maintaining latent infection predominantly in b lymphocytes. consequently, gammaherpesvirus pathogenesis is closely linked to normal b cell physiology. murine gammaherpesvirus 68 (mhv68) pathogenesis in laboratory mice has been extensively studied as a model system to gain insights into the nature of gammaherpesvirus infection ... | 2012 | 22952645 |
| an expanded myeloid derived suppressor cell population does not play a role in gammaherpesvirus-exacerbated breast cancer metastases. | mice latently infected with murine gammaherpesvirus 68 (hv-68) and transplanted with 4 t1 breast cancer cells developed exacerbated metastatic lesions when compared to controls. the mechanisms responsible for this viral-exacerbated disease were not clear. the ability of hv-68 infection to induce s100a8 and s100a9 production and to expand a population of cd11b+gr-1+ cells suggested that increased numbers, or activity, of viral-expanded myeloid derived suppressor cells (mdscs) might contribute to ... | 2012 | 22946998 |
| activation of the unfolded protein response by 2-deoxy-d-glucose inhibits kaposi's sarcoma-associated herpesvirus replication and gene expression. | lytic replication of the kaposi's sarcoma-associated herpesvirus (kshv) is essential for the maintenance of both the infected state and characteristic angiogenic phenotype of kaposi's sarcoma and thus represents a desirable therapeutic target. during the peak of herpesvirus lytic replication, viral glycoproteins are mass produced in the endoplasmic reticulum (er). normally, this leads to er stress which, through an unfolded protein response (upr), triggers phosphorylation of the α subunit of euk ... | 2012 | 22926574 |
| murine gammaherpesvirus 68 lana acts on terminal repeat dna to mediate episome persistence. | murine gammaherpesvirus 68 (mhv68) orf73 (mlana) has sequence homology to kaposi's sarcoma-associated herpesvirus (kshv) latency-associated nuclear antigen (lana). lana acts on the kshv terminal repeat (tr) elements to mediate kshv episome maintenance. disruption of mlana expression severely reduces the ability of mhv68 to establish latent infection in mice, consistent with the possibility that mlana mediates episome persistence. here we assess the roles of mlana and mhv68 tr (mtr) elements in e ... | 2012 | 22915819 |
| epidemiology and fitness effects of wood mouse herpesvirus in a natural host population. | rodent gammaherpesviruses have become important models for understanding human herpesvirus diseases. in particular, interactions between murid herpesvirus 4 and mus musculus (a non-natural host species) have been extensively studied under controlled laboratory conditions. however, several fundamental aspects of murine gammaherpesvirus biology are not well understood, including how these viruses are transmitted from host to host, and their impacts on host fitness under natural conditions. here, w ... | 2012 | 22915692 |
| experimental infection of laboratory-bred bank voles (myodes glareolus) with murid herpesvirus 4. | muhv-4 is a natural pathogen of rodents of the genus apodemus (e.g., wood mice, yellow-necked mice) and myodes glareolus (bank voles). we report experimental muhv-4 infection of bank voles in comparison with infection of a. sylvaticus (wood mice) and balb/c mice. like in wood mice, the level of productive replication in the lungs of bank voles was significantly lower than in balb/c mice. in contrast to other hosts, however, the level of latent infection in the lung and spleen of bank voles was e ... | 2012 | 22782137 |
| ctcf and sp1 interact with the murine gammaherpesvirus 68 internal repeat elements. | herpesviruses maintain a dynamic balance between latency and productive infection. this is a complex process regulated by viral and cellular factors. we have developed a murine gammaherpesvirus 68 (mhv-68) model system in which to study mechanisms underlying balance between latency and lytic infection. we have generated an epithelial cell line that carries mhv-68 in a tightly latent form by using a bacterial artificial chromosome clone of the virus genome with a mutation in the mhv-68 major lyti ... | 2012 | 22706977 |
| murine gammaherpesvirus 68 glycoprotein 150 does not contribute to latency amplification in vivo. | murine gammaherpesvirus 68 (mhv-68) is used as a model to study the function of gammaherpesvirus glycoproteins. gp150 of mhv-68, encoded by open reading frame m7, is a positional homolog of gp350/220 of ebv and of gp35/37 of kshv. since it had been proposed that gp350/220 of ebv might be a suitable vaccine antigen to protect from ebv-associated diseases, gp150 has been applied as a model vaccine in the mhv-68 system. when analyzing the function of gp150, previous studies yielded conflicting resu ... | 2012 | 22681851 |
| exacerbated metastatic disease in a mouse mammary tumor model following latent gammaherpesvirus infection. | | 2012 | 22642913 |