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malignant catarrhal fever of cattle is associated with low abundance of il-2 transcript and a predominantly latent profile of ovine herpesvirus 2 gene expression.malignant catarrhal fever (mcf) is a lethal disease of cattle, characterized by vasculitis, necrosis, and accumulation of activated, dysregulated cytotoxic lymphocytes in various tissues. ovine gamma herpesvirus 2 (ovhv-2) is a causative agent of mcf, which may trigger the disease through immunopathogenic pathways. lymphocytes are the main target of the virus. however, the pathogenic basis of the disease is still mysterious.200919603070
immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4.many acute viral infections can be controlled by vaccination; however, vaccinating against persistent infections remains problematic. herpesviruses are a classic example. here, we discuss their immune control, particularly that of gamma-herpesviruses, relating the animal model provided by murid herpesvirus-4 (muhv-4) to human infections. the following points emerge: (i) cd8(+) t-cell evasion by herpesviruses confers a prominent role in host defence on cd4(+) t cells. cd4(+) t cells inhibit muhv- ...200919605591
antibody limits in vivo murid herpesvirus-4 replication by igg fc receptor-dependent functions.antibody is an important antiviral defence. however, it is considered to do little against human gamma-herpesviruses, which establish predominantly latent infections regulated by t cells. one limitation on analysing these infections has been that latency is already well-established at clinical presentation; early infection may still be accessible to antibody. here, using murid herpesvirus-4 (muhv-4), we tested the impact of adoptively transferred antibody on early gamma-herpesvirus infection. im ...200919625459
lack of detectable equine herpesviruses 1 and 2 in paraffin-embedded specimens of equine sarcoidosis.equine sarcoidosis is a rare, multisystemic, noncaseating, granulomatous and lymphoplasmacytic disease of unknown etiology. a recent report described a horse with granulomatous skin disease displaying histologic, electron microscopic, and polymerase chain reaction (pcr) findings consistent with equine herpesvirus 2 (ehv-2).200919645844
prevalence of viremia and oral shedding of rhesus rhadinovirus and retroperitoneal fibromatosis herpesvirus in large age-structured breeding groups of rhesus macaques (macaca mulatta).we performed a cross-sectional study to estimate the prevalence of 2 gamma-2-herpesviruses, rhesus rhadinovirus (rrv) and retroperitoneal fibromatosis herpesvirus (rfhv), in breeding colonies of rhesus macaques. of 90 animals selected for sampling, 73 (81%) were positive for rrv, which was detected only in blood in 22 (24%), only in saliva in 15 (16%), and in both blood and saliva in 36 (40%). detection of rrv dna in blood and saliva was significantly higher in animals younger than 2 y. in compa ...200919712580
mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes m2 and m3 can reduce latent viral load.gammaherpesviruses establish life-long latent infections in their hosts. if the host becomes immunosuppressed, these viruses may reactivate and cause severe disease, and even in immunocompetent individuals the gammaherpesviruses are presumed to have an oncogenic potential. murine gammaherpesvirus-68 (mhv-68) is a member of the gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. two atte ...200919748577
equine gammaherpesviruses: pathogenesis, epidemiology and diagnosis.equine gammaherpesviruses (γehv) have been widely studied over the past 45 years and many isolates have been characterised. despite this, the diagnosis of γehv infection remains difficult to establish as its clinical manifestations lack specificity, ranging from mild respiratory signs in a small number of animals to outbreaks in large groups of young horses. this review focuses on the epidemiology, pathogenesis, clinical manifestations and diagnosis of equine herpesvirus (ehv)-2 and -5 infection ...201019766026
comparative pathobiology of kaposi sarcoma-associated herpesvirus and related primate rhadinoviruses.with the emergence of the aids epidemic over the last 2 decades and the more recent identification of kaposi sarcoma-associated herpesvirus (kshv, human herpesvirus 8), the genera of rhadinoviruses have gained importance as a family of viruses with oncogenic potential. first recognized in new world primates more than 30 y ago, the rhadinoviruses saimiriine herpesvirus 2 and ateline herpesvirus 2 have well-described transforming capabilities. recently several new species-specific rhadinoviruses o ...200819793454
viral bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.gamma-herpesviruses (gammahvs) have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies. one critical virulence factor involved in the persistency of murine gamma-herpesvirus 68 (gammahv68) is the viral homolog of the bcl-2 protein (vbcl-2), which has been implicated to counteract both host apoptotic responses and autophagy pathway. however, the relative significance of the two activities of v ...200919816569
equine disease surveillance, april to june 2009. 200919855110
viral interleukin-6 encoded by rhesus macaque rhadinovirus is associated with lymphoproliferative disorder (lpd).rhesus macaques (rm) co-infected with simian immunodeficiency virus (siv) and rhesus macaque rhadinovirus (rrv) develop abnormal cellular proliferations characterized as extra-nodal lymphoma and retroperitoneal fibromatosis (rf). rrv encodes a viral interleukin-6 (vil-6), much like kaposi's sarcoma-associated herpesvirus, and involvement of the viral cytokine was examined in proliferative lesions.200919863672
genetic diversity and molecular evolution of human and non-human primate gammaherpesvirinae.the gammaherpesvirinae sub-family is divided into two genera: lymphocryptovirus and rhadinovirus. until the middle of the 1990s, the rhadinovirus genus was only represented by herpesvirus saimiri and herpesvirus ateles, which infect new world monkey species. until the year 2000, epstein-barr virus (ebv), the human prototype of the lymphocryptovirus, and simian homologues had only been detected in humans and old world non-human primates. it was thought, therefore, that the separation of the conti ...201019879975
blimp-1-dependent plasma cell differentiation is required for efficient maintenance of murine gammaherpesvirus latency and antiviral antibody responses.recent evidence from the study of epstein-barr virus and kaposi's sarcoma-associated herpesvirus supports a model in which terminal differentiation of b cells to plasma cells leads to virus reactivation. here we address the role of blimp-1, the master transcriptional regulator of plasma cell differentiation, in murine gammaherpesvirus 68 (mhv68) latency and reactivation. blimp-1 expression in infected cells was dispensable for acute virus replication in the lung following intranasal inoculation ...201019889763
a global analysis of evolutionary conservation among known and predicted gammaherpesvirus micrornas.micrornas (mirnas) are small, noncoding rnas which posttranscriptionally regulate gene expression. the current release of the mirna registry lists 16 viruses which encode a total of 146 mirna hairpins. strikingly, 139 of these are encoded by members of the herpesvirus family, suggesting an important role for mirnas in the herpesvirus life cycle. however, with the exception of 7 mirna hairpins known to be shared by epstein-barr virus (ebv) and the closely related rhesus lymphocryptovirus (rlcv), ...201019889779
a novel herpesvirus in the sanctuary chimpanzees on ngamba island in uganda.recent studies in non-human primates have led to the discovery of novel primate herpesviruses. in order to get more information on herpesvirus infections in apes, we studied wild born captive chimpanzees.201019900168
the orf59 dna polymerase processivity factor homologs of old world primate rv2 rhadinoviruses are highly conserved nuclear antigens expressed in differentiated epithelium in infected macaques.orf59 dna polymerase processivity factor of the human rhadinovirus, kaposi's sarcoma-associated herpesvirus (kshv), is required for efficient copying of the genome during virus replication. kshv orf59 is antigenic in the infected host and is used as a marker for virus activation and replication.200919922662
tpl2/ap-1 enhances murine gammaherpesvirus 68 lytic replication.how cellular factors regulate gammaherpesvirus lytic replication is not well understood. here, through functional screening of a cellular kinase expression library, we identified mitogen-activated protein kinase kinase kinase 8 (map3k8/tpl2) as a positive regulator of murine gammaherpesvirus 68 (mhv-68 or gammahv-68) lytic gene expression and replication. tpl2 enhances mhv-68 lytic replication by upregulating lytic gene expression and promoter activities of viral lytic genes, including rta and o ...201019939924
characterization of a novel wood mouse virus related to murid herpesvirus 4.two novel gammaherpesviruses were isolated, one from a field vole (microtus agrestis) and the other from wood mice (apodemus sylvaticus). the genome of the latter, designated wood mouse herpesvirus (wmhv), was completely sequenced. wmhv had the same genome structure and predicted gene content as murid herpesvirus 4 (muhv4; murine gammaherpesvirus 68). overall nucleotide sequence identity between wmhv and muhv4 was 85 % and most of the 10 kb region at the left end of the unique region was particu ...201019940063
mature and functional viral mirnas transcribed from novel rna polymerase iii promoters.murid herpesvirus 4 (muhv-4) micrornas were previously cloned from latently infected tumor cells and predicted to be processed from a series of rna polymerase iii primary transcripts. we detected maturely processed muhv-4 mirnas within total rna from lytically infected cells in vitro and infected tissues ex vivo, using a highly sensitive reverse ligation meditated rt-pcr strategy. we determined that the muhv-4 micrornas are biologically active during infection by a luciferase reporter system. we ...201019948768
antiviral effect of recombinant equine interferon-gamma on several equine viruses.recombinant equine interferon-gamma (reifn-gamma) was prepared using a baculovirus expression system and its antiviral activity was investigated using several equine viruses. the reifn-gamma suppressed the replication of all equine viruses used in the present experiment in horse cell cultures, but did not affect the growth of host cells at concentrations of less than 1000 u/ml. a strong antiviral effect was observed, especially against rna viruses. equine picornavirus, equine rhinovirus and equi ...201020004981
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 ...201020015983
identification of a novel betaherpesvirus in mus musculus.rodent betaherpesviruses vary considerably in genomic content, and these variations can result in a distinct pathogenicity. therefore, the identification of unknown betaherpesviruses in house mice (mus musculus), the most important rodent host species in basic research, is of importance. during a search for novel herpesviruses in house mice using herpesvirus consensus pcr and attempts to isolate viruses in tissue culture, we identified a previously unknown betaherpesvirus. the primary pcr search ...200920025745
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 ...201020053740
characterization of cytoplasmic motifs important in rhesus rhadinovirus gb processing and trafficking.rhesus monkey rhadinovirus (rrv) is highly related to kaposi's sarcoma-associated herpesvirus (kshv), a human gamma-herpesvirus etiologically-linked with several cancers. glycoprotein b (gb) homologues are encoded by all herpesviruses and play a role in virus attachment, entry, and in egress. we have found that rrv gb, like kshv gb, is cleaved at a consensus furin cleavage site and is modified by both n-linked and o-linked glycosylation. mutagenesis of three tyrosine- based trafficking motifs, a ...201020060555
characterization of the rhesus fibromatosis herpesvirus march family member rfk3.retroperitoneal fibromatosis-associated herpesvirus (rfhv) is a gamma-herpesvirus of macaques that is closely related to kaposi's sarcoma-associated herpesvirus (kshv). herein, we present characterization of the k3 gene from rfhv, a homologue of the kshv k3 and k5 genes. like the kshv proteins, kk3 and kk5, the rfk3 protein decreases cell surface mhc i levels. similar to kk5, rfk3 also modulates icam-1, but not another kk5 target, b7.2. inhibitors of dynamin or mutations in the rfk3 ring-ch e3 u ...201020060556
autoexcision of bacterial artificial chromosome facilitated by terminal repeat-mediated homologous recombination: a novel approach for generating traceless genetic mutants of herpesviruses.infectious bacterial artificial chromosomes (bacs) of herpesviruses are powerful tools for genetic manipulation. however, the presence of bac vector sequence in the viral genomes often causes genetic and phenotypic alterations. while the excision of the bac vector cassette can be achieved by homologous recombination between extra duplicate viral sequences or loxp site-mediated recombination, these methods either are inefficient or leave a loxp site mark in the viral genome. here we describe the ...201020071577
a mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral micrornas.canonical primary microrna (pri-mirna) precursors are transcribed by rna polymerase ii and then processed by the drosha endonuclease to generate approximately 60 nt pre-mirna hairpins. pre-mirnas in turn are cleaved by dicer to generate mature mirnas. previously, some short introns, called mirtrons, were reported to fold into pre-mirna hairpins after splicing and debranching, and mirnas can also be excised by dicer cleavage of rare endogenous short hairpin rnas. here we report that the mirnas en ...201020129062
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/ ...201020130062
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 ...201020139098
rhadinovirus vector-derived human telomerase reverse transcriptase expression in primary t cells.the rhadinovirus herpesvirus saimiri (hvs) as a gene delivery vector allows large dna insertions and long-termed gene expression. in the case of t-cell transduction, such vectors use the viral transformation-associated genes of hvs c488 for t-cell amplification. in this report, we investigated whether the gene for the catalytic telomerase subunit human telomerase reverse transcriptase (htert) can substitute for the transformation-associated genes in rhadinoviral t-cell transduction and amplifica ...201020164858
episomal replication timing of gamma-herpesviruses in latently infected cells.this study addresses the timing of gammaherpesviral episomal dna replication with respect to the cell cycle. for the first time we analyzed a rhadinovirus, the prototype herpesvirus saimiri (hvs), and compared it to the lymphocryptovirus epstein-barr virus (ebv). newly synthesized dna of latently infected b- or t-cells was first brdu-labeled; then we sorted the cells corresponding to cell cycle phases g(0/1), g(2/m), and s (4 fractions s(1)-s(4)) and performed anti-brdu chromatin immunoprecipita ...201020172574
glycoprotein gene sequence variation in rhesus monkey rhadinovirus.gene sequences for seven glycoproteins from 20 independent isolates of rhesus monkey rhadinovirus (rrv) and of the corresponding seven glycoprotein genes from nine strains of the kaposi's sarcoma-associated herpesvirus (kshv) were obtained and analyzed. phylogenetic analysis revealed two discrete groupings of rrv gh sequences, two discrete groupings of rrv gl sequences and two discrete groupings of rrv gb sequences. we called these phylogenetic groupings gh(a), gh(b), gl(a), gl(b), gb(a) and gb( ...201020172576
persistent gamma-herpesvirus infection induces a cd4 t cell response containing functionally distinct effector populations.the direct effector mechanisms of cd4 t cells during gamma-herpesvirus 68 (gammahv68)-persistent infection are less well understood than those of their cd8 t cell counterparts, although there is substantial evidence that cd4 t cells are critical for the control of persistent gamma-herpesvirus infection. our results show that in gammahv68-persistently infected mice, cd4 t cells are not cytokine polyfunctional, but there is a division of labor in the cd4 t cell compartment in which cd4 t cells pol ...201020208003
induction of tgf-beta 1, not regulatory t cells, impairs antiviral immunity in the lung following bone marrow transplant.patients receiving hematopoietic stem cell transplantation or bone marrow transplantation (bmt) as therapy for various malignancies or autoimmune diseases have an increased risk for infectious complications posttransplant, especially in the lung. we have used bmt in mice and murine gammaherpesvirus, gammahv-68, to study the efficacy of adaptive immune responses post-bmt. five weeks posttransplant, mice have fully reconstituted their hematopoietic lineages in both the lung and periphery. when cha ...201020348421
accumulation of oxidized proteins in herpesvirus infected cells.oxidative stress gives rise to an environment that can be highly damaging to proteins, lipids, and dna. previous studies indicate that herpesvirus infections cause oxidative stress in cells and in tissues. the biological consequences of virus-induced oxidative stress have not been characterized. studies from many groups indicate that proteins which have been damaged through oxidative imbalances are either degraded by the 20s proteasome in a ubiquitin-independent fashion or form aggregates that a ...201020441790
isolation and partial sequencing of equid herpesvirus 5 from a horse in iceland.horses are hosts to 2 types of gammaherpesviruses, equid herpesvirus 2 and 5 (ehv-2 and ehv-5, respectively). both ehv-2 and ehv-5 are common in horses in iceland. an icelandic ehv-5 isolate was recovered by sequential culture in primary fetal horse kidney and rabbit kidney cells. glycoprotein b, glycoprotein h, and dna terminase genes of the isolate were fully sequenced, and the dna polymerase gene was partly sequenced. to date, the glycoprotein b gene of ehv-5 was the only gene that has been r ...201020453218
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 ...201020484501
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 ...201020519454
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 ...201020660200
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 ...201020686022
rhesus rhadinovirus infection of rhesus fibroblasts occurs through clathrin-mediated endocytosis.rhesus rhadinovirus (rrv) is a gammaherpesvirus closely related to kaposi's sarcoma-associated herpesvirus (kshv), an oncogenic virus linked to the development of kaposi's sarcoma and several other lymphoproliferative diseases, including primary effusion lymphoma and multicentric castleman's disease. rrv naturally infects rhesus macaques and induces lymphoproliferative diseases under experimental conditions, making it an excellent model for the study of kshv. unlike kshv, which grows poorly in c ...201020826690
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, ...201020668075
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 ...201020668074
comment on "induction of tgf-beta 1, not regulatory t cells, impairs antiviral immunity in the lung following bone marrow transplant". 201020660356
bid and bim collaborate during induction of t cell death in persistent infection.upon ag encounter, naive t cells undergo extensive ag-driven proliferation and can differentiate into effector cells. up to 95% of these cells die leaving a small residual population of t cells that provide protective memory. in this study, we investigated the contribution of the bh3-only family protein bid in the shutdown of t cell responses after acute and persistent infection. influenza virus pathogenicity has been proposed to be mediated by a peptide encoded in the basic polymerase (pb1-rf2) ...201121339359
analysis of rhesus rhadinovirus micrornas expressed in virus-induced tumors from infected rhesus macaques.rhesus rhadinovirus (rrv), a primate gamma-herpesvirus related to human kaposi's sarcoma-associated herpesvirus (kshv), causes a similar pattern of pathogenesis. previously, rrv was shown to express 7 pre-micrornas (pre-mirnas) in latently infected cells. using deep sequencing, we analyzed the pattern of small rna expression in vivo using latently rrv-infected b-cell lymphoma and retroperitoneal fibromatosis tissues. we identified 15 virally encoded pre-mirnas in both tumors, including all previ ...201020655562
the immune response of foals to natural infection with equid herpesvirus-2 and its association with febrile illness.equid herpesvirus-2 (ehv-2) infection is ubiquitous in horses. although ehv-2 infection has been associated with several disease syndromes, its true pathogenic significance in horses remains uncertain. epstein-barr virus (ebv), another gammaherpesvirus, has been shown to cause febrile illness in humans related to its immunopathologic effects. thus, the purpose of this study was to describe the ontogeny of the immune response of a cohort of 9 foals to natural infection with ehv-2 by evaluating se ...201020646766
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 ...201121471322
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 ...201121481326
bovine herpesvirus 4 orf73 is dispensable for virus growth in vitro, but is essential for virus persistence in vivo.orf73 orthologues encoded by different rhadinoviruses have been studied extensively. these studies revealed that the orf73 expression product (porf73) is a multifunctional protein essential for latency that enables episome tethering to mitotic chromosomes and modulates cellular pathways implicated in growth and survival of latently infected cells. comparison of porf73 orthologues encoded by rhadinoviruses reveals important variations in amino acid sequence length and composition. bovine herpesvi ...201020592111
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 ...201020573854
viral infection of the placenta leads to fetal inflammation and sensitization to bacterial products predisposing to preterm labor.pandemics pose a more significant threat to pregnant women than to the nonpregnant population and may have a detrimental effect on the well being of the fetus. we have developed an animal model to evaluate the consequences of a viral infection characterized by lack of fetal transmission. the experiments described in this work show that viral infection of the placenta can elicit a fetal inflammatory response that, in turn, can cause organ damage and potentially downstream developmental deficienci ...201020554966
detection and sequence analysis of equine gammaherpesviruses from horses with respiratory tract disease in turkey.the equid herpesvirus 2 (ehv-2) and 5 (ehv-5), identified agents of respiratory infections and keratoconjunctivitis cases in some equids, comprise a high degree of antigenic heterogeneity. prevalence and genetic characterization of ehv-2 and ehv-5 strains from turkey were investigated in this study. a total of 73 nasal swabs and 54 blood specimens were sampled from horses with respiratory tract diseases characterized by mucopurulent nasal discharge and occasional coughing. overall, ehv-2- and eh ...201020553426
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 ...201020552028
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 ...201020542255
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 ...201020538905
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 ...201020537410
the membrane-bound transcription factor creb3l1 is activated in response to virus infection to inhibit proliferation of virus-infected cells.creb3l1/oasis is a cellular transcription factor synthesized as a membrane-bound precursor and activated by regulated intramembrane proteolysis in response to stimuli like er stress. comparing gene expression between huh7 subclones that are permissive for hepatitis c virus (hcv) replication versus the nonpermissive parental huh7 cells, we identified creb3l1 as a host factor that inhibits proliferation of virus-infected cells. upon infection with diverse dna and rna viruses, including murine ?-he ...201121767813
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 ...201020534854
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 ...201020493722
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 ...201020444892
mhv-68 open reading frame 20 is a nonessential gene delaying lung viral clearance.recently, it has been demonstrated that the mhv-68 orf20-encoded gene product induces cell-cycle arrest at the g2/m phase, followed by apoptosis. to study the role of this conserved gene in vivo, two independent orf20-deficient mhv-68 viruses and their revertants were constructed. as the replication in vitro of both mutants followed similar kinetics to that of the wild-type and revertant viruses, orf20 is therefore a nonessential virus gene. no cell cycle arrest could be observed upon infection ...201021104281
cutting edge: virus-specific cd8+ t cell clones and the maintenance of replicative function during a persistent viral infection.persistent viral infections induce the differentiation and accumulation of large numbers of senescent cd8(+) t cells, raising the possibility that repetitive stimulation drives clones of t cells to senesce. it is therefore unclear whether t cell responses are maintained by the self-renewal of ag-experienced peripheral t cell subsets or by the continuous recruitment of newly generated naive t cells during chronic infections. using a transgenic mouse model that permits the indelible marking of gra ...201021068412
cutting edge: adaptive versus innate receptor signals selectively control the pool sizes of murine ifn-γ- or il-17-producing γδ t cells upon infection.γδ t lymphocytes are commonly viewed as embracing properties of both adaptive and innate immunity. contributing to this is their responsiveness to pathogen products, either with or without the involvement of the tcr and its coreceptors. this study clarifies this paradoxical behavior by showing that these two modes of responsiveness are the properties of two discrete sets of murine lymphoid γδ t cells. thus, myd88 deficiency severely impaired the response to malaria infection of cd27((-)), il-17a ...201021037088
latent infection by γherpesvirus stimulates profibrotic mediator release from multiple cell types.although γherpesvirus infections are associated with enhanced lung fibrosis in both clinical and animal studies, there is limited understanding about fibrotic effects of γherpesviruses on cell types present in the lung, particularly during latent infection. wild-type mice were intranasally infected with a murine γherpesvirus (γhv-68) or mock-infected with saline. twenty-eight days postinfection (dpi), ∼14 days following clearance of the lytic infection, alveolar macrophages (ams), mesenchymal ce ...201021036917
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 ...201020926565
interference with dendritic cell populations limits early antigen presentation in chronic γ-herpesvirus-68 infection.a critical factor influencing the ability of the host to mount a robust immune response against a virus depends on the rapid recruitment of dendritic cells (dcs) presenting ags. from the outset, this step sets the tempo for subsequent activation of virus-specific t cells. despite this, how induction of the immune response might be modified by pathogens with the capacity to establish persistence is unclear. in this study, we have characterized the in vivo influence of murine gamma-herpesvirus k3- ...201020720208
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 ...201120712808
murine gamma-herpesvirus 68 hijacks mavs and ikkbeta to initiate lytic replication.upon viral infection, the mitochondrial antiviral signaling (mavs)-ikkbeta pathway is activated to restrict viral replication. manipulation of immune signaling events by pathogens has been an outstanding theme of host-pathogen interaction. here we report that the loss of mavs or ikkbeta impaired the lytic replication of gamma-herpesvirus 68 (gammahv68), a model herpesvirus for human kaposi's sarcoma-associated herpesvirus and epstein-barr virus. gammahv68 infection activated ikkbeta in a mavs-de ...201020686657
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 ...201021106239
the dual functions of il-1 receptor-associated kinase 2 in tlr9-mediated ifn and proinflammatory cytokine production.bone marrow-derived plasmacytoid dendritic cells (pdcs) from il-1r-associated kinase (irak)2-deficient mice produced more ifns than did wild-type pdcs upon stimulation with the tlr9 ligand cpg. furthermore, in cpg-stimulated irak2-deficient pdcs there was increased nuclear translocation of ifn regulatory factor 7, the key transcription factor for ifn gene transcription in these cells. in irak2-deficient macrophages, enhanced nf-?b activation and increased expression of cpg-induced genes were det ...201121270393
klrg1+nkg2a+ cd8 t cells mediate protection and participate in memory responses during ?-herpesvirus infection.functional cd8 t cell effector and memory responses are generated and maintained during murine ?-herpesvirus 68 (?hv68) persistent infection despite continuous presentation of viral lytic ags. however, the identity of the cd8 t cell subpopulations that mediate effective recall responses and that can participate in the generation of protective memory to a ?-herpesvirus infection remains unknown. during ?hv68 persistence, ~75% of ?hv68-specific cd8 t cells coexpress the nk receptors killer cell le ...201121346231
genetic heterogeneity and variation in viral load during equid herpesvirus-2 infection of foals.equine herpesvirus-2 (ehv-2) infection has been implicated as a cause of a variety of clinical disorders in young horses, including upper respiratory tract disease, generalized malaise, fever, pharyngeal lymphoid hyperplasia, and lymphadenopathy. considerable sequence heterogeneity has been demonstrated previously among ehv-2 strains, and individual horses can be concurrently infected with more than one virus strain. in this study, the temporal variation of the viral load and genomic diversity o ...201120655670
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 ...201121439939
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 ...201121573023
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 ...201121593277
rhesus monkey rhadinovirus orf57 induces gh and gl glycoprotein expression through the post-transcriptional accumulation of target mrnas.open reading frame 57 (orf57) of gamma-2 herpesviruses is a key regulator of viral gene expression. it has been variously reported to enhance expression of viral genes by transcriptional, post-transcriptional, or translational activation mechanisms. previously we have shown that expression of gh and gl of rhesus monkey rhadinovirus, a close relative of the human kaposi's sarcoma-associated herpesvirus (kshv), could be dramatically rescued by codon optimization as well as by orf57 co-expression. ...201121613403
kinetics of equid herpesvirus type 2 infections in a group of thoroughbred foals.the significance of infection with equid herpevirus 2 (ehv-2) remains unresolved, mainly due to its widespread distribution, and frequent isolation of the virus not only from diseased animals, but also from clinically normal horses. it has been suggested that ehv-2 exerts its effects on the host indirectly, through predisposition to secondary infections. the aim of this study was to determine kinetics of ehv-2 infection among foals and to investigate the role that ehv-2 may play in development o ...201121616610
gammaherpesviruses of new world primatesnumerous gamma-herpesviruses, a large subfamily of the herpes group, have limited pathogenic potential upon primary infection of their natural host. they are most relevant however as tumor viruses of the hematopoietic system and form an important chapter of viral oncology. the prototype of the genus lymphocryptovirus (γ1-herpesvirus), epstein-barr virus (ebv), was the first clearly identified human herpesvirus. ebv causes lymphomas of b-cell origin and other lymphoproliferati ...200721348092
gammaherpesviruses entry and early events during infectionthe two human gammaherpesviruses, epstein–barr virus (ebv), a gamma 1 lymphocryptovirus and kaposi’s sarcoma associated virus (kshv), a gamma 2 rhadinovirus, have many features in common. they share an architecture that is typical of all members of the herpesvirus family, they share an ability to establish latency in lymphocytes, and they are both initiators or potentiators of human tumors. for the virologist some of the challenges they present are the same, in particular ...200721348095
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 ...201121666062
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 ...201121811408
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 ...201121748596
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 ...201122018782
Viral Interferon Regulatory Factors decrease the induction of Type I and Type II IFN during Rhesus Macaque Rhadinovirus Infection.Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV), two closely related ?-herpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs). To assess the role of the vIRFs during de novo infection, we have utilized the bacterial artificial chromosome clone of RRV(17577) (WT(BAC) RRV) to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV). Infection of primary rhesus fibrob ...201122156526
Gammaherpesvirus gene expression and DNA synthesis are facilitated by viral protein kinase and histone variant H2AX.Gammaherpesvirus protein kinases are an attractive therapeutic target as they support lytic replication and latency. Via an unknown mechanism these kinases enhance expression of select viral genes and DNA synthesis. Importantly, the kinase phenotypes have not been examined in primary cell types. Mouse gammaherpesvirus-68 (MHV68) protein kinase orf36 activates the DNA damage response (DDR) and facilitates lytic replication in primary macrophages. Significantly, H2AX, a DDR component and putative ...201121943826
herpesvirus saimiri infection of rhesus macaques: a model for acute rhadinovirus-induced t-cell transformation and oncogenesis.herpesvirus saimiri (hvs) causes acute lymphoma and leukemia upon experimental infection of various monkey species. hvs strain c488 is also capable of transforming human t-lymphocytes to stable growth in culture. the most susceptible species for oncogenesis are new world primates, in particular the cottontop tamarin (saguinus oedipus). however, old world monkeys such as macaques are the most used animal model for the close-to-human situation. the limited data on hvs infection in old world monkey ...201121915869
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 ...201121830899
longitudinal patterns of viremia and oral shedding of rhesus rhadinovirus and retroperitoneal fibromatosis herpesviruses in age-structured captive breeding populations of rhesus macaques (macaca mulatta).rhesus rhadinovirus (rrv) and retroperitoneal fibromatosis herpesvirus (rfhv), 2 closely related +¦2 herpesviruses, are endemic in breeding populations of rhesus macaques at our institution. we previously reported significantly different prevalence levels, suggesting the transmission dynamics of rrv and rfhv differ with regard to viral shedding and infectivity. we designed a longitudinal study to further examine the previously observed differences between rrv and rfhv prevalence and the potentia ...201121819683
Microtubule- and Dynein-dependent nuclear trafficking of rhesus rhadinovirus in rhesus fibroblasts.We investigated the role of microtubules in rhesus rhadinovirus (RRV) nuclear trafficking in rhesus fibroblasts. Intact microtubules and microtubule dynamics are required for RRV trafficking to perinuclear regions. RRV trafficking was reduced by an inhibitor of the dynein motor and overexpression of dynamitin. Furthermore, RRV particles are colocalized with microtubules and dynein proteins. These results highlight the important roles of microtubules and dynein-dynactin complexes in the transport ...201222031929
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 ...201121849446
Alpha and gamma herpesvirus detection in two herds of farmed red deer (Cervus elaphus) in New Zealand.Abstract201222175434
viral irfs are critical for delay of the host immune response against rhesus macaque rhadinovirus.kaposi's sarcoma-associated herpesvirus (kshv), and the closely related γ2-herpesvirus, rhesus macaque rhadinovirus (rrv), are the only known viruses to encode viral homologues of the cellular interferon (ifn) regulatory factors (irfs). recent characterization of a virf deletion clone of rrv (virf-ko rrv) demonstrated that virfs inhibit induction of type i and type ii ifn during rrv infection of peripheral blood mononuclear cells. because the ifn response is a key component to a host's antiviral ...201122171275
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 ...201122205754
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 ...201121849436
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 ...201121931547
vaccine protection against simian immunodeficiency virus in monkeys using recombinant gamma-2 herpesvirus.recombinant strains of replication-competent rhesus monkey rhadinovirus (rrv) were constructed in which strong promoter/enhancer elements were used to drive expression of simian immunodeficiency virus (siv) env or gag or a rev-tat-nef fusion protein. cultured rhesus monkey fibroblasts infected with each recombinant strain were shown to express the expected protein. three rrv-negative and two rrv-positive rhesus monkeys were inoculated intravenously with a mixture of these three recombinant rrvs. ...201121900170
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