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the dynamics of murid gammaherpesvirus 4 within wild, sympatric populations of bank voles and wood mice.murid gammaherpesvirus 4 (muhv-4) is widely used as a small animal model for understanding gammaherpesvirus infections in man. however, there have been no epidemiological studies of the virus in wild populations of small mammals. as muhv-4 both infects cells associated with the respiratory and immune systems and attempts to evade immune control via various molecular mechanisms, infection may reduce immunocompetence with potentially serious fitness consequences for individuals. here we report a l ...200717347391
epstein-barr virus bglf4 kinase induces premature chromosome condensation through activation of condensin and topoisomerase ii.previous studies of epstein-barr virus (ebv) replication focused mainly on the viral and cellular factors involved in replication compartment assembly and controlling the cell cycle. however, little is known about how ebv reorganizes nuclear architecture and the chromatin territories. in ebv-positive nasopharyngeal carcinoma na cells or akata cells, we noticed that cellular chromatin becomes highly condensed upon ebv reactivation. in searching for the possible mechanisms involved, we found that ...200717360754
control of virus reactivation arrests pulmonary herpesvirus-induced fibrosis in ifn-gamma receptor-deficient mice.idiopathic pulmonary fibrosis (ipf) is a chronic progressive fibrotic lung disorder of unknown cause. several studies suggest an association between epstein-barr virus pulmonary infection and the development of ipf.200717363768
[equine herpesvirus 2: a study on the relation between viral excretion and respiratory disease in thoroughbred horses].equine herpesvirus 2 (ehv-2) was isolated from healthy animals; therefore, the association between ehv-2 infection and respiratory disease raises the question of the role of this agent in this pathology. to date, there are no reports that relate viral excretion to health, this study then analysed 153 nasal swabs from horses in different age groups (older and younger than 1 year old) and state of health (clinically healthy and with respiratory symptoms). results showed that the percentage of hors ...200617370575
immunohistochemical study of experimental malignant catarrhal fever in rabbits.malignant catarrhal fever (mcf) is an often-fatal lymphoproliferative disease of a variety of ungulates that occurs worldwide. it is caused by either of the highly related but distinct gammaherpesviruses alcelaphine herpesvirus-1 (alhv-1, wildebeest reservoir) or ovine herpesvirus-2 (ovhv-2, sheep reservoir). mcf in rabbits is an excellent model as it closely resembles the disease in susceptible ungulates that include cattle, deer and bison. in this study, newly available and previously characte ...200717374379
cd8+ t cell dysfunction and increase in murine gammaherpesvirus latent viral burden in the absence of 4-1bb ligand.studies of costimulatory receptors belonging to the tnfr family have revealed their diverse roles in affecting different stages of the t cell response. the 4-1bb ligand (4-1bbl)/4-1bb pathway has emerged as a receptor-ligand pair that impacts not the initial priming, but later phases of the t cell response, such as sustaining clonal expansion and survival, maintaining memory cd8(+) t cells, and supporting secondary expansion upon ag challenge. although the role of this costimulatory pathway in c ...200717404306
epstein-barr virus thymidine kinase is a centrosomal resident precisely localized to the periphery of centrioles.the thymidine kinase (tk) encoded by epstein-barr virus (ebv) differs not only from that of the alphaherpesviruses but also from that of the gamma-2 herpesvirus subfamily. because cellular location is frequently a determinant of regulatory function, to gain insight into additional role(s) of ebv tk and to uncover how the lymphocryptovirus and rhadinovirus enzymes differ, the subcellular localizations of ebv tk and the related cercopithecine herpesvirus-15 tk were investigated. we show that in co ...200717428875
murine gammaherpesvirus 68 contains two functional lytic origins of replication.a 1.25-kbp dna fragment from the right side of the genome containing the lytic origin of replication (orilyt) of murine gammaherpesvirus 68 (mhv-68) has been identified by a plasmid replication assay. here we show that a mutant mhv-68 with a deletion of an essential part of this orilyt, generated by using an mhv-68 bacterial artificial chromosome, was only slightly attenuated and still able to replicate but that a mutant containing an additional deletion on the left side of the genome was replic ...200717442722
cloning and analysis of micrornas encoded by the primate gamma-herpesvirus rhesus monkey rhadinovirus.several pathogenic human herpesviruses have recently been shown to express virally encoded micrornas in infected cells. although the function of these micrornas is largely unknown, they are hypothesized to play a role in mediating viral replication by downregulating cellular mrnas encoding antiviral factors. here, we report the cloning and analysis of micrornas encoded by rhesus monkey rhadinovirus (rrv), an animal virus model for the pathogenic human gamma-herpesvirus kaposi's sarcoma-associate ...200717451774
control of rta expression critically determines transcription of viral and cellular genes following gammaherpesvirus infection.the replication and transcriptional activator (rta), encoded by orf50 of gammaherpesviruses, initiates the lytic cycle of gene expression; therefore understanding the impact of rta on viral and cellular gene expression is key to elucidating the transcriptional events governing productive infection and reactivation from latency. to this end, the impact of altering rta transcription on viral and cellular gene expression was studied in the context of a whole virus infection. recombinant murine gamm ...200717485528
identification of novel rodent herpesviruses, including the first gammaherpesvirus of mus musculus.rodent herpesviruses such as murine cytomegalovirus (host, mus musculus), rat cytomegalovirus (host, rattus norvegicus), and murine gammaherpesvirus 68 (hosts, apodemus species) are important tools for the experimental study of human herpesvirus diseases. however, alphaherpesviruses, roseoloviruses, and lymphocryptoviruses, as well as rhadinoviruses, that naturally infect mus musculus (house mouse) and other old world mice are unknown. to identify hitherto-unknown rodent-associated herpesviruses ...200717507487
malignant catarrhal fever-like lesions associated with ovine herpesvirus-2 infection in three goats.this is the first description of malignant catarrhal fever-like lesions associated with ovine herpesvirus-2 (ovhv-2) infection in goats with central nervous symptoms. the diagnosis was based on typical histological lesions characterized by systemic lymphohistiocytic and fibrinoid vasculitis and confirmed by polymerase chain reaction and subsequent phylogenetic analysis of the detected ovhv-2 sequences.200717543478
murine gammaherpesvirus-68 productively infects immature dendritic cells and blocks maturation.many viruses have evolved mechanisms to evade host immunity by subverting the function of dendritic cells (dcs). this study determined whether murine gammaherpesvirus-68 (gamma hv-68) could infect immature or mature bone-marrow-derived dcs and what effect infection had on dc maturation. it was found that gamma hv-68 productively infected immature dcs, as evidenced by increased viral titres over time. if dcs were induced to mature by exposure to lps and then infected with gamma hv-68, only a smal ...200717554020
igg fc receptors provide an alternative infection route for murine gamma-herpesvirus-68.herpesviruses can be neutralized in vitro but remain infectious in immune hosts. one difference between these settings is the availability of immunoglobulin fc receptors. the question therefore arises whether a herpesvirus exposed to apparently neutralizing antibody can still infect fc receptor(+) cells.200717593961
phase-dependent immune evasion of herpesviruses.viruses employ various modes to evade immune detection. two possible evasion modes are a reduction of the number of epitopes presented and the mimicry of host epitopes. the immune evasion efforts are not uniform among viral proteins. the number of epitopes in a given viral protein and the similarity of the epitopes to host peptides can be used as a measure of the viral attempts to hide this protein. using bioinformatics tools, we here present a genomic analysis of the attempts of four human herp ...200717609281
type i interferon inhibition and dendritic cell activation during gammaherpesvirus respiratory infection.the respiratory tract is a major mucosal site for microorganism entry into the body, and type i interferon (ifn) and dendritic cells constitute a first line of defense against viral infections. we have analyzed the interaction between a model dna virus, plasmacytoid dendritic cells, and type i ifn during lung infection of mice. our data show that murine gammaherpesvirus 68 (gammahv68) inhibits type i ifn secretion by dendritic cells and that plasmacytoid dendritic cells are necessary for convent ...200717626106
murine gammaherpesvirus 68 orf52 encodes a tegument protein required for virion morphogenesis in the cytoplasm.the tegument, a semiordered matrix of proteins overlying the nucleocapsid and underlying the virion envelope, in viruses in the gamma subfamily of herpesviridae is poorly understood. murine gammaherpesvirus 68 (mhv-68) is a robust model for studying gammaherpesvirus virion structure, assembly, and composition, as mhv-68 efficiently completes the lytic phase and productively infects cultured cells. we have found that mhv-68 orf52 encodes an abundant tegument protein conserved among gammaherpesvir ...200717634243
the orf49 protein of murine gammaherpesvirus 68 cooperates with rta in regulating virus replication.our functional mapping study of murine gammaherpesvirus 68 (mhv-68, or gammahv-68) revealed that a mutant harboring a transposon at the orf49 locus (orf49(null)) evidenced a highly attenuated in vitro growth. orf49 resides adjacent to and in an opposite direction from rta, the primary switch of the gammaherpesvirus life cycle. a flag-tagged orf49 protein was able to transcomplement orf49(null), and a revertant of orf49(null) restored its attenuated growth to a level comparable to that of the wil ...200717634244
myocarditis in newborn wild-type balb/c mice infected with the murine gamma herpesvirus mhv-68.animal models of human epstein-barr virus (ebv) infection include ebv infection of primates and infection of mice with mhv-68, a further gamma herpesvirus (gamma-hv). we aimed at extending the mhv-68 model to study gamma-hv-related cardiac disease.200717658501
the murine gammaherpesvirus-68 gp150 acts as an immunogenic decoy to limit virion neutralization.herpesviruses maintain long-term infectivity without marked antigenic variation. they must therefore evade neutralization by other means. immune sera block murine gammaherpesvirus-68 (mhv-68) infection of fibroblasts, but fail to block and even enhance its infection of igg fc receptor-bearing cells, suggesting that the antibody response to infection is actually poor at ablating virion infectivity completely. here we analyzed this effect further by quantitating the glycoprotein-specific antibody ...200717684552
sequence analysis of the equid herpesvirus 2 chemokine receptor homologues e1, orf74 and e6 demonstrates high sequence divergence between field isolates.equid herpesvirus 2 (ehv-2), in common with other members of the subfamily gammaherpesvirinae, encodes homologues of cellular seven-transmembrane receptors (7tmr), namely open reading frames (orfs) e1, 74 and e6, which each show some similarity to cellular chemokine receptors. whereas orf74 and e6 are members of gammaherpesvirus-conserved 7tmr gene families, e1 is currently unique to ehv-2. to investigate their genetic variability, ehv-2 7tmrs from a panel of equine gammaherpesvirus isolates wer ...200717698654
orf73-null murine gammaherpesvirus 68 reveals roles for mlana and p53 in virus replication.gammaherpesviruses establish lifelong, latent infections in host lymphocytes, during which a limited subset of viral gene products facilitates maintenance of the viral episome. among the gamma-2-herpesvirus (rhadinovirus) subfamily, this includes expression of the conserved orf73-encoded lana proteins. we previously demonstrated by loss-of-function mutagenesis that the murine gammaherpesvirus 68 (mhv68) orf73 gene product, mlana, is required for the establishment of latency following intranasal ...200717699571
a gammaherpesviral internal repeat contributes to latency amplification.gammaherpesviruses cause important infections of humans, in particular in immunocompromised patients. the genomes of gammaherpesviruses contain variable numbers of internal repeats whose precise role for in vivo pathogenesis is not well understood.200717710133
discovery of herpesviruses in multi-infected primates using locked nucleic acids (lna) and a bigenic pcr approach.targeting the highly conserved herpes dna polymerase (dpol) gene with pcr using panherpes degenerate primers is a powerful tool to universally detect unknown herpesviruses. however, vertebrate hosts are often infected with more than one herpesvirus in the same tissue, and pan-herpes dpol pcr often favors the amplification of one viral sequence at the expense of the others. here we present two different technical approaches that overcome this obstacle: (i) pan-herpes dpol pcr is carried out in th ...200717822523
discovery of herpesviruses in bats.seven novel gammaherpesviruses (ghv) and one novel betaherpesvirus were discovered in seven different european bat species (order chiroptera, family vespertilionidae) with a pan-herpesvirus pcr assay, targeting the dna polymerase (dpol) gene. the sequences of six bat ghv were similarly related to members of the gammaherpesvirus genera percavirus and rhadinovirus. the seventh ghv was related to the porcine lymphotropic herpesvirus 1 (genus macavirus). the betaherpesvirus appeared to be a distant ...200717872515
evidence for a multiprotein gamma-2 herpesvirus entry complex.herpesviruses use multiple virion glycoproteins to enter cells. how these work together is not well understood: some may act separately or they may form a single complex. murine gammaherpesvirus 68 (mhv-68) gb, gh, gl, and gp150 all participate in entry. gb and gl are involved in binding, gb and gh are conserved fusion proteins, and gp150 inhibits cell binding until glycosaminoglycans are engaged. here we show that a gh-specific antibody coprecipitates gb and thus that gh and gb are associated i ...200717898071
expression of neuronal trace amine-associated receptor (taar) mrnas in leukocytes.trace amines such as tyramine, octopamine and beta-phenylethylamine bind with high affinity to the mammalian trace amine-associated receptor 1 (taar1), potentially activating g-proteins in the synaptic membranes of target neurons. recently there has been significant interest in taar1, since this receptor can bind certain psychoactive drugs of abuse such as ecstasy (3,4-methylenedioxymethamphetamine). surprisingly, ecstasy has been shown to alter responses of immune cells, and we questioned wheth ...200717900709
murine gammaherpesvirus 68 genes both induce and suppress lymphoproliferative disease.gammaherpesvirus infection is associated with an increased incidence of lymphoproliferative disease in immunocompromised hosts. murine gammaherpesvirus 68 (gammahv68) infection of balb beta(2)-microglobulin-deficient (balb beta(2)m(-/-)) mice provides an animal model for analysis of the mechanisms responsible for the induction of a lymphoproliferative disease, atypical lymphoid hyperplasia (alh), that is pathologically similar to posttransplant lymphoproliferative disease associated with epstein ...200817977975
differential regulation of the cyclin-dependent kinase inhibitors p21(cip1) and p27(kip1) by phosphorylation directed by the cyclin encoded by murine herpesvirus 68.members of the gamma2-herpesvirus family encode cyclin-like proteins that have the ability to deregulate mammalian cell cycle control. here we report the key features of the viral cyclin encoded by murine herpesvirus 68, m cyclin. m cyclin preferentially associated with and activated cdk2; the m cyclin/cdk2 holoenzyme displayed a strong reliance on phosphorylation of the cdk t loop for activity. cdk2 associated with m cyclin exhibited substantial resistance to the cdk inhibitor proteins p21(cip) ...200817997402
transcriptional control by the r-transactivator protein of alcelaphine herpesvirus-1. 200818027098
antibody evasion by the n terminus of murid herpesvirus-4 glycoprotein b.herpesviruses characteristically transmit infection from immune hosts. although their success in escaping neutralization by pre-formed antibody is indisputable, the underlying molecular mechanisms remain largely unknown. glycoprotein b (gb) is the most conserved component of the herpesvirus entry machinery and its n terminus (gb-nt) is a common neutralization target. we used murid herpesvirus-4 to determine how gb-nt contributes to the virus-antibody interaction. deleting gb-nt had no obvious im ...200718034158
detection of ovine herpesvirus 2 major capsid gene transcripts as an indicator of virus replication in shedding sheep and clinically affected animals.the aim of this study was to identify tissues where ovine herpesvirus 2 (ovhv-2) replication occurs in vivo. a reverse-transcriptase pcr targeting the ovhv-2 major capsid protein gene (orf 25) was developed and the presence of transcripts used as an indicator of virus replication in naturally infected sheep, and cattle and bison with sheep-associated malignant catarrhal fever (sa-mcf). orf 25 transcripts were detected in 18 of 60 (30%) turbinate, trachea, and lung samples from five sheep experie ...200818054405
sequence analysis of the regions flanking terminal repeats of the genome of umava isolate of murine gammaherpesvirus.the umava isolate of murine gammaherpesvirus (mhv-umava) slightly differs from murine gammaherpesvirus 68 (mhv-68) and two other isolates of murine gammaherpesvirus (mhv), mhv-76 and mhv-72 in some biological properties. to identify the region(s) in the mhv-umava genome responsible for this phenomenon, we compared the sequences flanking terminal repeats (trs) of the mhv-umava genome with those of mhv-68, mhv-76 and mhv-72. restriction and sequence analyses revealed in mhv-umava as compared to mh ...200718076303
unique structures in a tumor herpesvirus revealed by cryo-electron tomography and microscopy.gammaherpesviruses, including the human pathogens epstein-barr virus and kaposi's sarcoma-associated herpesvirus, are causative agents of lymphomas and other malignancies. the structural characterization of these viruses has been limited due to difficulties in obtaining adequate amount of virion particles. here we report the first three-dimensional structural characterization of a whole gammaherpesvirus virion by an emerging integrated approach of cryo-electron tomography combined with single-pa ...200818096403
selection of mutant cho clones resistant to murine gammaherpesvirus 68 infection.murine gammaherpesvirus 68 (mhv68) is used as a model to study gammaherpesvirus pathogenesis both in tissue culture systems and in vivo. we used a gene-trapping approach to get insight into cellular factors involved in mhv68 infection. by generating a library of gene-trapped cho cells, we were able to isolate several clones that exhibited various degrees of resistance to mhv68-induced cytopathic effect. clones that showed the highest degree of resistance were affected at the early stage of the v ...200818191980
murine gammaherpesvirus 68 serum antibodies in general human population.previous studies using elisa and virus neutralization test (vnt) have proved the presence of murine gammaherpesvirus 68 (mhv-68) serum antibodies in sera of laboratory staff working with mhv-68, as well as in the general population. in this study, we investigated the incidence of serum antibodies to mhv-68 and to human herpesviruses presumably antigenically similar to mhv-68, as herpes simplex virus 1 (hsv-1), human cytomegalovirus (hcmv), and epstein-barr virus (ebv), in general population usin ...200718197737
[humanes herpesvirus 8 (hhv-8) and kaposi sarcoma].the kaposi sarcoma-associated herpes virus (kshv) or human herpesvirus 8 (hhv-8) is a gamma-herpesvirus (rhadinovirus) present in all clinical cases of kaposi sarcoma (ks). hhv-8 can be transmitted by blood and blood products, as well as in saliva during mother-child transfer. sexual transmission is also possible although not conclusively proven. actually the goal of treating ks is to reduce symptoms and, not to produce complete tumor remission. in patients with hiv- and posttransplant-associate ...200818209996
up-regulation of murid herpesvirus 4 orf50 by hypoxia: possible implication for virus reactivation from latency.murid herpesvirus 4 (muhv-4) is a member of the gammaherpesvirus subfamily capable to establish a long-lasting latency and induce occasional malignancies. because muhv-4 is associated with cancer in a subset of virus-infected mice and because tumor development is often linked with hypoxia, we studied the influence of hypoxia on the biology of this virus. using immunofluorescence and facs analysis we detected increased proportion of muhv-4 positive cells in the latently infected nb-78 cell line e ...200818221814
systematic mutagenesis of the murine gammaherpesvirus 68 m2 protein identifies domains important for chronic infection.murine gammaherpesvirus 68 (mhv68) infection of inbred mice represents a genetically tractable small-animal model for assessing the requirements for the establishment of latency, as well as reactivation from latency, within the lymphoid compartment. by day 16 postinfection, mhv68 latency in the spleen is found in b cells, dendritic cells, and macrophages. however, as with epstein-barr virus, by 3 months postinfection mhv68 latency is predominantly found in isotype-switched memory b cells. the mh ...200818234799
impact of infections and normal flora in nonhuman primates on drug development.preclinical safety studies that are required for the marketing approval of a pharmaceutical include single and repeat dose studies in rodent and nonrodent species. the use of nonhuman primates (nhps), primarily macaques, as the nonrodent species has increased in recent years, in part due to the increase in development of biopharmaceuticals and immunomodulatory agents. depending on the source of the macaques, they may vary in genetic background, normal flora, and/or the incidence of preexisting p ...200818323580
murine gammaherpesvirus 68 open reading frame 75c tegument protein induces the degradation of pml and is essential for production of infectious virus.promyelocytic leukemia nuclear body (pml nb) proteins mediate an intrinsic cellular host defense response against virus infections. herpesviruses express proteins that modulate pml or pml-associated proteins by a variety of strategies, including degradation of pml or relocalization of pml nb proteins. the consequences of pml-herpesvirus interactions during infection in vivo have yet to be investigated in detail, largely because of the species-specific tropism of many human herpesviruses. murine ...200818508901
cd40 engagement on dendritic cells, but not on b or t cells, is required for long-term control of murine gammaherpesvirus 68.cd4 t cells are not essential for primary clearance of replicating murine gammaherpesvirus 68 (mhv-68) but are required for effective long-term control. the virus reactivates in the lungs of major histocompatibility complex class ii-deficient (cii-/-) mice that lack functional cd4 t cells. cd40 ligand (cd40l) is upregulated on activated cd4 t cells, and it is thought that cd40-cd40l interactions are an important component of cd4 t-cell help. our previous studies have shown that agonistic antibod ...200818768977
rhesus macaque rhadinovirus-associated non-hodgkin lymphoma: animal model for kshv-associated malignancies.rhesus macaque rhadinovirus (rrv) is closely related to kaposi sarcoma-associated herpesvirus (kshv) and is associated with the development of b-cell hyperplasia and persistent lymphadenopathy resembling multicentric castleman disease in rhesus macaques (rms) coinfected with simian immunodeficiency virus (siv). here we investigated whether rms experimentally infected with siv and rrv can develop other disease manifestations observed in hiv- and kshv-infected patients. as reported earlier, inocul ...200818757778
the murid herpesvirus-4 gl regulates an entry-associated conformation change in gh.the glycoprotein h (gh)/gl heterodimer is crucial for herpesvirus membrane fusion. yet how it functions is not well understood. the murid herpesvirus-4 gh, like that of other herpesviruses, adopts its normal virion conformation by associating with gl. however, gh switched back to a gl-independent conformation after virion endocytosis. this switch coincided with a conformation switch in gb and with capsid release. virions lacking gl constitutively expressed the down-stream form of gh, prematurely ...200818665235
equid herpesvirus 2-associated oral and esophageal ulceration in a foal.a case of a 1-month-old thoroughbred foal with dysphagia, salivation, pyrexia, oral mucosal pustules, and esophageal ulceration is reported. swabs from the ulcerated lesions yielded equid herpesvirus 2 (ehv-2) in virus isolation assays, and histopathology of a biopsy from the esophageal lesion identified nuclear inclusions suggestive of herpesviruses. immunohistochemical staining with antibodies specific for ehv-2 was positive for epithelial cells in the vicinity of the ulcer but not in more dis ...200818987236
ovine herpesvirus 2 replicates initially in the lung of experimentally infected sheep.ovine herpesvirus 2 (ovhv-2), a rhadinovirus in the subfamily gammaherpesvirinae, is the causative agent of sheep-associated malignant catarrhal fever (sa-mcf), a frequently fatal lymphoproliferative disease primarily of ruminants worldwide. inability to propagate the virus in vitro has made it difficult to study ovhv-2 replication. aerosol inoculation of sheep with ovhv-2 from nasal secretions collected from naturally infected sheep during shedding episodes results in infection of naive sheep, ...200818559941
establishment of b-cell lines latently infected with reactivation-competent murine gammaherpesvirus 68 provides evidence for viral alteration of a dna damage-signaling cascade.gammaherpesvirus 68 (gammahv68, or mhv68) is a naturally occurring rodent pathogen that replicates to high titer in cell culture and is amenable to in vivo experimental evaluation of viral and host determinants of gammaherpesvirus disease. however, the inability of mhv68 to transform primary murine b cells in culture, the absence of a robust cell culture latency system, and the paucity of mhv68-positive tumor cell lines have limited an understanding of the molecular mechanisms by which mhv68 mod ...200818495760
extreme dependence of gh and gl expression on orf57 and association with highly unusual codon usage in rhesus monkey rhadinovirus.standard vectors for high-level expression elicited undetectable levels of the gh and gl glycoproteins of rhesus monkey rhadinovirus (rrv) following transient-transfection assays under a variety of conditions. these same vectors and conditions yielded high levels of rrv gb expression. unlike other genes of rrv, both the gh and gl genes were noted to have a highly aberrant, suboptimal codon usage. high levels of rrv gh and gl expression were achieved by two alternative means: codon optimization o ...200818480451
identification of closely spaced but distinct transcription initiation sites for the murine gammaherpesvirus 68 latency-associated m2 gene.murine gammaherpesvirus 68 (mhv68) infection of mice provides a tractable small-animal system for assessing viral requirements for establishment of and reactivation from latency. the m2 gene product has no homology to any known proteins but has been shown to play a role in both the establishment of mhv68 latency and reactivation from latency. furthermore, we have recently shown that m2 expression in primary murine b cells leads to enhanced proliferation, survival, and differentiation toward a pr ...200818480430
glycoprotein b switches conformation during murid herpesvirus 4 entry.herpesviruses are ancient pathogens that infect all vertebrates. the most conserved component of their entry machinery is glycoprotein b (gb), yet how gb functions is unclear. a striking feature of the murid herpesvirus 4 (muhv-4) gb is its resistance to neutralization. here, we show by direct visualization of infected cells that the muhv-4 gb changes its conformation between extracellular virions and those in late endosomes, where capsids are released. specifically, epitopes on its n-terminal c ...200818474550
an essential role for the proximal but not the distal cytoplasmic tail of glycoprotein m in murid herpesvirus 4 infection.murid herpesvirus-4 (muhv-4) provides a tractable model with which to define common, conserved features of gamma-herpesvirus biology. the multi-membrane spanning glycoprotein m (gm) is one of only 4 glycoproteins that are essential for muhv-4 lytic replication. gm binds to gn and is thought to function mainly secondary envelopment and virion egress, for which several predicted trafficking motifs in its c-terminal cytoplasmic tail could be important. we tested the contribution of the gm cytoplasm ...200818461133
infection of neonates with murine gammaherpesvirus 68 results in enhanced viral persistence in lungs and absence of infectious mononucleosis syndrome.we used the murine gammaherpesvirus 68 (gammahv-68), which serves as a model for human gammaherpesvirus infection, to determine whether age at infection altered the pattern of gammaherpesvirus pathogenesis. we infected mice intranasally at 8 days old (pups) and 6 weeks old (adults) to investigate differences in gammahv-68 pathogenesis. there was no difference between adults or pups in acute infection in the lungs at 6 days post-infection (p.i.). however, mice infected as pups exhibited a more di ...200818420788
the mhv68 m2 protein drives il-10 dependent b cell proliferation and differentiation.murine gammaherpesvirus 68 (mhv68) establishes long-term latency in memory b cells similar to the human gammaherpesvirus epstein barr virus (ebv). ebv encodes an interleukin-10 (il-10) homolog and modulates cellular il-10 expression; however, the role of il-10 in the establishment and/or maintenance of chronic ebv infection remains unclear. notably, mhv68 does not encode an il-10 homolog, but virus infection has been shown to result in elevated serum il-10 levels in wild-type mice, and il-10 def ...200818389062
study of equid herpesviruses 2 and 5 in iceland with a type-specific polymerase chain reaction.the horse population in iceland is a special breed, isolated from other horses for at least 1000 years. this provides an exceptional opportunity to investigate old and new pathogens in an inbred herd with few infectious diseases. we have developed a high sensitivity semi-nested pcr to study equid gammaherpesviruses 2 and 5 (ehv-2 and 5) in iceland. the first pcr is group specific, the second type-specific, targeting a 113bp sequence in the glyb gene. dna isolated from white blood cells and 18 di ...200818336849
production and utilization of interleukin-15 in malignant catarrhal fever.malignant catarrhal fever (mcf) is an often fatal lymphoproliferative disease of ungulates caused by either alcelaphine herpesvirus-1 (alhv-1) or ovine herpesvirus-2 (ovhv-2). the pathogenesis of mcf is poorly understood, but appears to involve an auto-destructive pathology whereby cytotoxic lymphocytes destroy areas of a variety of tissues. the cytokine interleukin-15 (il-15) is involved in the development and maintenance of cytotoxic lymphocytes and may therefore have a role in the pathogenesi ...200818331739
prevalence of ovine herpesvirus type 2 in north-west portugal. 200818310564
the murid herpesvirus-4 gh/gl binds to glycosaminoglycans.the first contact a virus makes with cells is an important determinant of its tropism. murid herpesvirus-4 (muhv-4) is highly dependent on glycosaminoglycans (gags) for cell binding. its first contact is therefore likely to involve a gag-binding virion glycoprotein. we have previously identified two such proteins, gp70 and gp150. gp70 binds strongly to gags. however, deleting it makes little difference to muhv-4 cell binding or gag-dependence. deleting gp150, by contrast, frees muhv-4 from gag d ...200818301747
gamma-herpesvirus-induced protection against bacterial infection is transient.herpesviruses are widely disseminated in the population and establish lifelong latency, which is associated with a variety of pathological consequences. a recent report showed that mice latently infected with either murine gamma-herpesvirus-68 (gammahv68) or murine cytomegalovirus (mcmv), mouse pathogens genetically similar to the human herpesviruses, epstein-barr virus, kaposi's sarcoma-associated herpesvirus, and cytomegalovirus, had enhanced resistance to subsequent bacterial infection, sugge ...200919210230
expansion of effector memory tcr vbeta4+ cd8+ t cells is associated with latent infection-mediated resistance to transplantation tolerance.therapies that control largely t cell-dependent allograft rejection in humans also possess the undesirable effect of impairing t cell function, leaving transplant recipients susceptible to opportunistic viruses. prime among these opportunists are the ubiquitous herpesviruses. to date, studies are lacking that address the effect of viruses that establish a true latent state on allograft tolerance or the effect of tolerance protocols on the immune control of latent viruses. by using a mixed chimer ...200818292543
role for myd88 signaling in murine gammaherpesvirus 68 latency.toll-like receptors (tlrs) are known predominantly for their role in activating the innate immune response. recently, tlr signaling via myd88 has been reported to play an important function in development of a b-cell response. since b cells are a major latency reservoir for murine gammaherpesvirus 68 (mhv68), we investigated the role of tlr signaling in the establishment and maintenance of mhv68 latency in vivo. mice deficient in myd88 (myd88(-/-)) or tlr3 (tlr3(-/-)) were infected with mhv68. a ...200818256152
structural and biochemical bases for the inhibition of autophagy and apoptosis by viral bcl-2 of murine gamma-herpesvirus 68.all gammaherpesviruses express homologues of antiapoptotic b-cell lymphoma-2 (bcl-2) to counter the clearance of infected cells by host antiviral defense machineries. to gain insights into the action mechanisms of these viral bcl-2 proteins, we carried out structural and biochemical analyses on the interactions of m11, a viral bcl-2 of murine gamma-herpesvirus 68, with a fragment of proautophagic beclin1 and bcl-2 homology 3 (bh3) domain-containing peptides derived from an array of proapoptotic ...200818248095
the cd8 t-cell response against murine gammaherpesvirus 68 is directed toward a broad repertoire of epitopes from both early and late antigens.infection of mice with murine gammaherpesvirus 68 (mhv-68) robustly activates cd8 t cells, but only six class i major histocompatibility complex (mhc)-restricted epitopes have been described to date for the widely used h-2(b) haplotype mice. to explore the specificity and kinetics of the cytotoxic t-lymphocyte response in mhv-68-infected c57bl/6 mice, we screened for h-2k(b)- and h-2d(b)-restricted epitopes using a set of 384 candidate epitopes in an mhc tetramer-based approach and identified 19 ...200818922872
a single cd8+ t cell epitope sets the long-term latent load of a murid herpesvirus.the pathogenesis of persistent viral infections depends critically on long-term viral loads. yet what determines these loads is largely unknown. here, we show that a single cd8+ t cell epitope sets the long-term latent load of a lymphotropic gamma-herpesvirus, murid herpesvirus-4 (muhv-4). the muhv-4 m2 latency gene contains an h2-kd -restricted t cell epitope, and wild-type but not m2(-) muhv-4 was limited to very low level persistence in h2d mice. mutating the epitope anchor residues increased ...200818846211
primary clearance of murine gammaherpesvirus 68 by pkctheta-/- cd8 t cells is compromised in the absence of help from cd4 t cells.cd4 t cells are dispensable for acute control of murine gammaherpesvirus 68 (mhv-68) but are necessary for effective long-term control of the virus by cd8 t cells. in contrast, protein kinase c theta (pkctheta) is not essential for either acute or long-term viral control. however, we found that while either cd4 or cd8 t cells could mediate the clearance of mhv-68 from the lungs of pkctheta(+/+) mice, pkctheta(-/-) mice depleted of either subset failed to clear the virus. these data suggest that ...200818818318
molecular basis of the regulation of beclin 1-dependent autophagy by the gamma-herpesvirus 68 bcl-2 homolog m11.gamma-herpesviruses (gammahvs), including important human pathogens such as epstein barr virus, kaposi's sarcoma-associated hv, and the murine gammahv68, encode homologs of the antiapoptotic, cellular bcl-2 (cbcl-2) to promote viral replication and pathogenesis. the precise molecular details by which these proteins function in viral infection are poorly understood. autophagy, a lysosomal degradation pathway, is inhibited by the interaction of cbcl-2s with a key autophagy effector, beclin 1, and ...200818797192
endothelial cells support persistent gammaherpesvirus 68 infection.a variety of human diseases are associated with gammaherpesviruses, including neoplasms of lymphocytes (e.g. burkitt's lymphoma) and endothelial cells (e.g. kaposi's sarcoma). gammaherpesvirus infections usually result in either a productive lytic infection, characterized by expression of all viral genes and rapid cell lysis, or latent infection, characterized by limited viral gene expression and no cell lysis. here, we report characterization of endothelial cell infection with murine gammaherpe ...200818787698
in vivo attenuation of recombinant murine gammaherpesvirus 68 (mhv-68) is due to the expression and immunogenicity but not to the insertion of foreign sequences.recombinant herpesviruses are increasingly utilized to study herpesvirus biology. for recombinant viruses carrying insertions of foreign sequences, attenuated phenotypes in vivo have been frequently observed. in most cases, the underlying mechanisms were not clear or have not been investigated. in this study, we used a recombinant murine gammaherpesvirus 68 (mhv-68), carrying a cassette for the expression of the non-structural protein ns3 of hepatitis c virus (mhv-68-ns3), to systematically addr ...200818774154
gammaherpesvirus modulation of mouse adenovirus type 1 pathogenesis.immune function is likely to be shaped by multiple infections over time. infection with one pathogen can confer cross-protection against heterologous pathogens. we tested the hypothesis that latent murine gammaherpesvirus 68 (gammahv68) infection modulates host inflammatory responses and susceptibility to mouse adenovirus type 1 (mav-1). mice were infected intranasally (i.n.) with gammahv68. 21 days later, they were infected i.n. with mav-1. we assessed cytokine and chemokine expression by quant ...200818768196
alternatively initiated gene 50/rta transcripts expressed during murine and human gammaherpesvirus reactivation from latency.in the process of characterizing the requirements for expression of the essential immediate-early transcriptional activator (rta) encoded by gene 50 of murine gammaherpesvirus 68 (mhv68), a recombinant virus was generated in which the known gene 50 promoter was deleted (g50pko). surprisingly, the g50pko mutant retained the ability to replicate in permissive murine fibroblasts, albeit with slower kinetics than wild-type mhv68. 5'-rapid amplification of cdna ends analyses of rna prepared from g50p ...200918971285
herpesviruses in respiratory liquids of horses: putative implication in airway inflammation and association with cytological features.the objectives of this study were to estimate the prevalence and the potential role of equine herpesviruses (ehvs) detection in both bronchoalveolar lavage (bal) and tracheal wash (tw). the population included a control group (ctl; 37 tw and 25 bal) and a pathological group (pat; 259 tw and 387 bal), including horses either suffering from respiratory diseases including syndrome of tracheal inflammation, inflammatory airway disease, recurrent airway obstruction, or submitted to respiratory invest ...200919427139
a sequence-independent in vitro transposon-based strategy for efficient cloning of genomes of large dna viruses as bacterial artificial chromosomes.bacterial artificial chromosomes (bacs) derived from genomes of large dna viruses are powerful tools for functional delineation of viral genes. current methods for cloning the genomes of large dna viruses as bacs require prior knowledge of the viral sequences or the cloning of viral dna fragments, and are tedious because of the laborious process of multiple plaque purifications, which is not feasible for some fastidious viruses. here, we describe a novel method for cloning the genomes of large d ...200918988631
multiple functions for orf75c in murid herpesvirus-4 infection.all gamma-herpesviruses encode at least one homolog of the cellular enzyme formyl-glycineamide-phosphoribosyl-amidotransferase. murid herpesvirus-4 (muhv-4) encodes 3 (orfs 75a, 75b and 75c), suggesting that at least some copies have acquired new functions. here we show that the corresponding proteins are all present in virions and localize to infected cell nuclei. despite these common features, orfs 75a and 75b did not substitute functionally for a lack of orf75c, as orf75c virus knockouts were ...200818648660
characterization of the complement inhibitory function of rhesus rhadinovirus complement control protein (rcp).rhesus rhadinovirus (rrv) is currently the closest known, fully sequenced homolog of human kaposi sarcoma-associated herpesvirus. both these viruses encode complement inhibitors as follows: kaposi sarcoma-associated herpesvirus-complement control protein (kcp) and rrv-complement control protein (rcp). previously we characterized in detail the functional properties of kcp as a complement inhibitor. here, we performed comparative analyses for two variants of rcp protein, encoded by rrv strains h26 ...200918990693
quantitative imaging of single, unstained viruses with coherent x rays.we report the recording and reconstruction of x-ray diffraction patterns from single, unstained viruses, for the first time. by separating the diffraction pattern of the virus particles from that of their surroundings, we performed quantitative and high-contrast imaging of a single virion. the structure of the viral capsid inside a virion was visualized. this work opens the door for quantitative x-ray imaging of a broad range of specimens from protein machineries and viruses to cellular organell ...200818999646
cd8+ t cell immunity to epstein-barr virus and kaposi's sarcoma-associated herpes virus.gammaherpesviruses are agents which have evolved to persist within the lymphoid system and many have oncogenic potential; studying gammaherpesvirus infections therefore has the potential to reveal much about the workings of the immune system and the control over viral oncogenesis. the lymphocryptovirus epstein-barr virus (ebv) and the rhadinovirus kaposi's sarcoma-associated herpesvirus (kshv, also known as human herpesvirus 8) are the two human gammaherpesviruses. analysis of the t cell respons ...200819007888
the alcelaphine herpesvirus-1 orf 57 encodes a nuclear shuttling protein.alcelaphine herpesvirus-1 (alhv-1) is a gamma(2) rhadinovirus associated with malignant catarrhal fever (mcf) in cattle. orf 57 is well conserved among gammaherpesviruses and it has been shown that the orf 57 gene products of herpesvirus saimiri (hvs), kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv) play an important role in regulating viral gene expression. the alhv-1 orf 57 gene product has not been characterized. in the accompanying paper we have demonstrated that ...200919031003
high-resolution functional profiling of a gammaherpesvirus rta locus in the context of the viral genome.gammaherpesviruses kaposi's sarcoma-associated herpesvirus and epstein-barr virus are associated with multiple human cancers. our goal was to develop a quantitative, high-throughput functional profiling system to identify viral cis-elements and protein subdomains critical for virus replication in the context of the herpesvirus genome. in gamma-2 herpesviruses, the transactivating factor rta is essential for initiation of lytic gene expression and viral reactivation. we used the rta locus as a mo ...200919073723
in vivo imaging of murid herpesvirus-4 infection.luciferase-based imaging allows a global view of microbial pathogenesis. we applied this technique to gammaherpesvirus infection by inserting a luciferase expression cassette into the genome of murine herpesvirus-4 (muhv-4). the recombinant virus strongly expressed luciferase in lytically infected cells without significant attenuation. we used it to compare different routes of virus inoculation. after intranasal infection of anaesthetized mice, luciferase was expressed in the nose and lungs for ...200919088269
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
orf30 and orf34 are essential for expression of late genes in murine gammaherpesvirus 68.a hallmark of productive infection by dna viruses is the coupling of viral late gene expression to genome replication. here we report the identification of open reading frame 30 (orf30) and orf34 as viral trans factors crucial for activating late gene transcription following viral dna replication during lytic infection of murine gammaherpesvirus 68 (mhv-68). the mutant virus lacking either orf30 or orf34 underwent normal dna replication but failed to express viral late gene transcripts, leading ...200919091863
selective uptake of small rna molecules in the virion of murine gammaherpesvirus 68.noncoding rnas are a feature of many herpesvirus genomes. they include micrornas, whose function is the subject of intense investigation, in addition to longer rna molecules such as the epstein-barr virus-encoded rnas and herpesvirus saimiri u rnas, which have been known for some time but whose function is still not well defined. murine gammaherpesvirus 68 (mhv-68) encodes eight viral trna-like molecules (vtrnas) of unknown function. investigating the kinetics of expression of the vtrnas, we obs ...200919109392
identification of the nuclear export and adjacent nuclear localization signals for orf45 of kaposi's sarcoma-associated herpesvirus.open reading frame 45 (orf45) of kaposi's sarcoma-associated herpesvirus 8 (kshv) is an immediate-early phosphorylated tegument protein and has been shown to play important roles at both early and late stages of viral infection. homologues of orf45 exist only in gammaherpesviruses, and their homology is limited. these homologues differ in their protein lengths and subcellular localizations. we and others have reported that kshv orf45 is localized predominantly in the cytoplasm, whereas its homol ...200919116250
detection of a novel bat gammaherpesvirus in hungary.this paper describes the detection of a novel herpesvirus in a serotine bat (eptesicus serotinus) in hungary. the rescued animal showed signs of icterus and anorexia and died within a day, in spite of immediate supportive therapy. autopsy confirmed the clinical picture by the major lesions observed in the liver. histopathology revealed vacuolar degeneration in the hepatocytes and leukocytosis in the sinusoidal lumina. by electron microscopy, hydropic degeneration and apoptotic cells with a pycno ...200819149107
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
targeting mitotic chromosomes: a conserved mechanism to ensure viral genome persistence.viruses that maintain their genomes as extrachromosomal circular dna molecules and establish infection in actively dividing cells must ensure retention of their genomes within the nuclear envelope in order to prevent genome loss. the loss of nuclear membrane integrity during mitosis dictates that paired host cell chromosomes are captured and organized by the mitotic spindle apparatus before segregation to daughter cells. this prevents inaccurate chromosomal segregation and loss of genetic materi ...200919203914
conserved herpesviral kinase promotes viral persistence by inhibiting the irf-3-mediated type i interferon response.a conserved herpesviral kinase, designated orf36 in murine gamma-herpesvirus 68 (mhv-68), plays multiple vital roles in the viral life cycle. here, we show by screening mutant viruses that orf36 counteracts the antiviral type i interferon (ifn) response. orf36 specifically binds to the activated form of interferon regulatory factor 3 (irf-3) in the nucleus, inhibiting irf-3 interaction with the cotranscriptional activator cbp and thereby suppressing the recruitment of rna polymerase ii to the in ...200919218087
glycoprotein l sets the neutralization profile of murid herpesvirus 4.antibodies readily neutralize acute, epidemic viruses, but are less effective against more indolent pathogens such as herpesviruses. murid herpesvirus 4 (muhv-4) provides an accessible model for tracking the fate of antibody-exposed gammaherpesvirus virions. glycoprotein l (gl) plays a central role in muhv-4 entry: it allows gh to bind heparan sulfate and regulates fusion-associated conformation changes in gh and gb. however, gl is non-essential: heparan sulfate binding can also occur via gp70, ...200919264603
murid herpesvirus-4 lacking thymidine kinase reveals route-dependent requirements for host colonization.gammaherpesviruses infect at least 90 % of the world's population. infection control is difficult, in part because some fundamental features of host colonization remain unknown, for example whether normal latency establishment requires viral lytic functions. since human gammaherpesviruses have narrow species tropisms, answering such questions requires animal models. murid herpesvirus-4 (muhv-4) provides one of the most tractable. muhv-4 genomes delivered to the lung or peritoneum persist without ...200919264614
identification and functional characterization of a spliced rhesus rhadinovirus gene with homology to the k15 gene of kaposi's sarcoma-associated herpesvirus.rhesus monkey rhadinovirus (rrv) is a gamma-2 herpesvirus related to the human kaposi's sarcoma-associated herpesvirus (kshv or human herpesvirus 8). this study identified an alternatively spliced gene at the right side of the rrv genome (strain 17577) between open reading frame 75 and the terminal repeat region. of its eight exons, the first seven encoded up to 12 transmembrane domains, whilst the eighth exon encoded a predicted c-terminal cytoplasmic domain. structurally and positionally, this ...200919264656
nf-kappab p50 plays distinct roles in the establishment and control of murine gammaherpesvirus 68 latency.nf-kappab signaling is critical to the survival and transformation of cells infected by the human gammaherpesviruses epstein-barr virus and kaposi's sarcoma-associated herpesvirus. here we have examined how elimination of the nf-kappab transcription factor p50 from mice affects the life cycle of murine gammaherpesvirus 68 (mhv68). notably, mice lacking p50 in every cell type were unable to establish a sufficiently robust immune response to control mhv68 infection, leading to high levels of laten ...200919264770
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
identification and functional characterization of the left origin of lytic replication of murine gammaherpesvirus 68.murine gammaherpesvirus 68 (mhv-68) replicates robustly in cell culture, providing a model for studying viral genome replication during de novo infection of tumor-associated herpesviruses. we have previously identified a 1.25-kb origin of lytic replication (orilyt) for mhv-68. to further investigate the molecular mechanism of viral genome replication, we first fine-mapped essential cis-elements from this orilyt fragment using a transposon-mediated high-density mutagenesis method. the result prov ...200919285330
protective antigen-independent cd8 t cell memory is maintained during {gamma}-herpesvirus persistence.ag persistence during high-titer chronic viral infections induces cd8 t cell dysfunction and lack of ag-independent cd8 t cell memory formation. however, we have a poor understanding of the generation and maintenance of cd8 t cell memory during asymptomatic persistent viral infections, particularly gamma-herpesvirus infections. in this study, we demonstrate that the continuous presence of cognate ag in the host is not required for the maintenance of cd8 t cell memory during a persistent gamma-he ...200919299697
identification of infected b-cell populations by using a recombinant murine gammaherpesvirus 68 expressing a fluorescent protein.infection of inbred mice with murine gammaherpesvirus 68 (mhv68) has proven to be a powerful tool to study gammaherpesvirus pathogenesis. however, one of the limitations of this system has been the inability to directly detect infected cells harvested from infected animals. to address this issue, we generated a transgenic virus that expresses the enhanced yellow fluorescent protein (yfp), driven by the human cytomegalovirus immediate-early promoter and enhancer, from a neutral locus within the v ...200919386718
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
the chemokine-binding protein m3 as a tool to understand the chemokine network in vivo.murine herpesvirus 68 (mhv-68) codes for a secreted chemokine-binding protein, termed m3, which interacts with a broad range of chemokines with very high affinity, inhibiting chemokine function both in vitro and in vivo. here we describe the transgenic methodology used to study the role of m3 as an immune modulator in vivo.200919446726
chemokine receptor ccr7 contributes to a rapid and efficient clearance of lytic murine gamma-herpes virus 68 from the lung, whereas bronchus-associated lymphoid tissue harbors virus during latency.murine gamma-herpes virus 68 is a natural rodent pathogen closely related to the human gamma-herpes viruses kaposi's sarcoma-associated herpes virus and ebv. by intranasally infecting wild-type and ccr7-deficient mice, we investigated whether ccr7 is necessary for viral clearance from the lung and the establishment of latency. we found during the lytic phase of infection that inflammation in lungs of ccr7(-/-) mice was more severe and viral load significantly higher compared with wild-type litte ...200919454682
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
replication of equine herpesvirus type 1 in equine dermal cells transfected with bam hi[g] restriction fragment of ehv-2 genome.in previous experiments, we have demonstrated that the presence of equine herpesvirus 2 (ehv-2) enhanced plaque formation in cell cultures infected with equine herpesvirus type 1. to determine whether a specific region of the ehv-2 genome is responsible for this effect, we have constructed a library of bam hi fragments of the ehv-2 genome ligated into pcdna plasmid. equine dermal (ed) cell cultures were subsequently transfected with the constructs, passaged 5 times, tested for the presence of th ...200919459446
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