Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| identification of an rta responsive promoter involved in driving gammahv68 v-cyclin expression during virus replication. | among the distinguishing characteristics of members of the gamma-2 herpesvirus family is the expression of a mammalian d-type cyclin homolog, termed v-cyclin. murine gammaherpesvirus 68 (gammahv68) is a gamma2-herpesvirus that can infect inbred and outbred strains of mice, providing a genetic system for the study of gammaherpesvirus pathogenesis. disruption of the v-cyclin gene of gammahv68 results in a virus that establishes latency in infected mice to wild-type levels, but is severely attenuat ... | 2007 | 17477952 |
| 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 ... | 2007 | 17507487 |
| herpesvirus latency confers symbiotic protection from bacterial infection. | all humans become infected with multiple herpesviruses during childhood. after clearance of acute infection, herpesviruses enter a dormant state known as latency. latency persists for the life of the host and is presumed to be parasitic, as it leaves the individual at risk for subsequent viral reactivation and disease. here we show that herpesvirus latency also confers a surprising benefit to the host. mice latently infected with either murine gammaherpesvirus 68 or murine cytomegalovirus, which ... | 2007 | 17507983 |
| 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 ... | 2007 | 17554020 |
| 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 ... | 2007 | 17609281 |
| 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 ... | 2007 | 17626106 |
| a functional ubiquitin-specific protease embedded in the large tegument protein (orf64) of murine gammaherpesvirus 68 is active during the course of infection. | all herpesviruses contain a ubiquitin (ub)-specific cysteine protease domain embedded within their large tegument protein, based on homology with the corresponding sequences of ul36 from herpes simplex virus type 1 and m48 from murine cytomegalovirus. this type of activity has yet to be demonstrated for cells infected with a gammaherpesvirus. by activity-based profiling, we show that the large tegument protein of murine gammaherpesvirus (mhv-68) orf64 (273 kda) is a functional deubiquitinating p ... | 2007 | 17634221 |
| 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 ... | 2007 | 17634243 |
| 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 ... | 2007 | 17634244 |
| 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 ... | 2007 | 17684552 |
| structural and functional studies of the abundant tegument protein orf52 from murine gammaherpesvirus 68. | the tegument is a layer of proteins between the nucleocapsid and the envelope of herpesviruses. the functions of most tegument proteins are still poorly understood. in murine gammaherpesvirus 68, orf52 is an abundant tegument protein of 135 residues that is required for the assembly and release of infectious virus particles. to help understand the molecular basis for the function of this protein, we have determined its crystal structure at 2.1 a resolution. the structure reveals a dimeric associ ... | 2007 | 17699518 |
| 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 ... | 2007 | 17699571 |
| 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. | 2007 | 17710133 |
| 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 ... | 2007 | 17898071 |
| the rta/orf50 transactivator proteins of the gamma-herpesviridae. | the replication and transcription activator protein, rta, is encoded by orf50 in kaposi's sarcoma-associated herpesvirus (kshv) and other known gammaherpesviruses including epstein-barr virus (ebv), rhesus rhadinovirus (rrv), herpesvirus saimiri (hvs), and murine herpesvirus 68 (mhv-68). each rta/orf50 homologue of each gammaherpesvirus plays a pivotal role in the initiation of viral lytic gene expression and lytic reactivation from latency. here we discuss the rta/orf50 of kshv in comparison to ... | 2007 | 17089794 |
| murine gammaherpesvirus-68 inhibits antigen presentation by dendritic cells. | dendritic cells (dcs) play a central role in initiating adaptive immunity. murine gammaherpesvirus-68 (mhv-68), like many persistent viruses, infects dcs during normal host colonization. it therefore provides a means to understanding what host and viral genes contribute to this aspect of pathogenesis. the infected dc phenotype is likely to depend on whether viral gene expression is lytic or latent and whether antigen presentation is maintained. for mhv-68, neither parameter has been well defined ... | 2007 | 17940612 |
| 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 ... | 2007 | 18076303 |
| 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 ... | 2007 | 18197737 |
| glycoprotein l disruption reveals two functional forms of the murine gammaherpesvirus 68 glycoprotein h. | the herpesvirus glycoprotein h (gh) and gl associate to form a heterodimer that plays a central role in virus-driven membrane fusion. when archetypal alpha- or betaherpesviruses lack gl, gh misfolds and progeny virions are noninfectious. in order to define the role that gl plays in gamma-2 herpesvirus infections, we disrupted its coding sequence in murine gammaherpesvirus-68 (mhv-68). mhv-68 lacking gl folded gh into a conformation antigenically distinct from the form that normally predominates ... | 2007 | 17050601 |
| murine gammaherpesvirus-68 infection alters self-antigen presentation and type 1 diabetes onset in nod mice. | recent research in line with the "hygiene hypothesis" has implicated virus infection in the delay or prevention of autoimmunity in murine models of type 1 diabetes such as the nod mouse. we found that intraperitoneal or intranasal infection of nod mice with the murine gammaherpesvirus-68 (mhv-68) significantly delayed diabetes onset in an age-dependent manner. the acute phase following intraperitoneal infection was associated with significantly reduced trafficking of autoreactive bdc2.5nod cd4(+ ... | 2007 | 18025175 |
| 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 ... | 2007 | 18034158 |
| protective vaccination with hepatitis c virus ns3 but not core antigen in a novel mouse challenge model. | efficient vaccines against hepatitis c virus (hcv) infection are urgently needed. vaccine development has been hampered by the lack of suitable small animal models to reliably test the protective capacity of immmunization. | 2008 | 18076128 |
| 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 ... | 2008 | 18221814 |
| 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 ... | 2008 | 18234799 |
| 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 ... | 2008 | 18256152 |
| ecstasy (3,4-methylenedioxymethamphetamine) limits murine gammaherpesvirus-68 induced monokine expression. | while ecstasy (3,4-methylenedioxymethamphetamine, mdma) has been shown to modulate immune responses, no studies have addressed drug-induced alterations to viral infection. in this study, bone marrow-derived macrophages were exposed to mdma, then infected with murine gammaherpesvirus-68, and the expression of monokines assessed. mdma-induced reductions in virus-stimulated monokine mrna expression were observed in a dose-dependent manner. in particular, il-6 mrna expression and secretion was signi ... | 2008 | 18280699 |
| the gammaherpesvirus m2 protein manipulates the fyn/vav pathway through a multidocking mechanism of assembly. | to establish latent infections in b-cells, gammaherpesviruses express proteins in the infected b-cells of the host that spuriously activate signalling pathways located downstream of the b-cell receptor. one such protein is m2, a murine gammaherpesvirus 68-encoded molecule that activates the vav1/rac1 pathway via the formation of trimolecular complexes with scr family members. previous reports have shown that the formation of this heteromolecular complex involves interactions between a proline ri ... | 2008 | 18301737 |
| 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 ... | 2008 | 18301747 |
| induction of tachykinin production in airway epithelia in response to viral infection. | 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 lung challenge has been previously demonstrated but has been focused predominantly on the release of the tachykinins from nerves innervating the lung. we have previously demonstrated the most dramatic phenotype described for the substance p encoding gene preprotachykinin-a (ppt-a) to date in contro ... | 2008 | 18320026 |
| a gammaherpesvirus-secreted activator of vbeta4+ cd8+ t cells regulates chronic infection and immunopathology. | little is known about herpesvirus modulation of t cell activation in latently infected individuals or the implications of such for chronic immune disorders. murine gammaherpesvirus 68 (mhv68) elicits persistent activation of cd8(+) t cells bearing a vbeta4(+) t cell receptor (tcr) by a completely unknown mechanism. we show that a novel mhv68 protein encoded by the m1 gene is responsible for vbeta4(+) cd8(+) t cell stimulation in a manner reminiscent of a viral superantigen. during infection, m1 ... | 2008 | 18332178 |
| 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 ... | 2008 | 18389062 |
| 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 ... | 2008 | 18420788 |
| murine gammaherpesvirus-induced fibrosis is associated with the development of alternatively activated macrophages. | murine gammaherpesvirus 68 (mhv-68) is a natural pathogen of rodents closely related to the human gammaherpesviruses kaposi's sarcoma-associated herpesvirus and ebv. following intranasal infection, the virus replicates in the lung epithelium prior to establishing latent infection in lymphoid tissue. infection of mice deficient in ifn-gammar signaling (ifn-gammar-/-) results in a multiple organ fibrosis, in which the spleen is severely affected. we show here that by day 12 postinfection, prior to ... | 2008 | 18436582 |
| 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 ... | 2008 | 18461133 |
| 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 ... | 2008 | 18474550 |
| 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 ... | 2008 | 18480430 |
| 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 ... | 2008 | 18495760 |
| 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 ... | 2008 | 18508901 |
| rvsv(m delta 51)-m3 is an effective and safe oncolytic virus for cancer therapy. | oncolytic vesicular stomatitis virus (vsv) is being developed as a novel therapeutic agent for cancer treatment, although it is toxic in animals when administered systemically at high doses. its safety can be substantively improved by an m delta 51 deletion in the viral genome, and yet vsv(m delta 51) induces a much greater, robust cellular inflammatory response in the host than wild-type vsv, which severely attenuates its oncolytic potency. we have reported that the oncolytic potency of wild-ty ... | 2008 | 18533893 |
| a replication-defective gammaherpesvirus efficiently establishes long-term latency in macrophages but not in b cells in vivo. | murine gammaherpesvirus 68 (gammahv68 or mhv68) is genetically related to the human gammaherpesviruses epstein-barr virus (ebv) and kaposi's sarcoma-associated herpesvirus (kshv), providing a useful system for in vivo studies of the virus-host relationship. to begin to address fundamental questions about the mechanisms of the establishment of gammaherpesvirus latency, we previously generated a replication-defective gammahv68 lacking the expression of the single-stranded dna binding protein encod ... | 2008 | 18562537 |
| chemokine-binding activities of m3 protein encoded by murine gammaherpesvirus 72. | murine gammaherpesvirus 68 (mhv-68) contains gene-encoding m3 protein expressed during the acute and persistent phase of infection. this protein features a chemokine-binding activities (parry et al., 2000; van berkel et al., 2000). in this study, we demonstrated that the murine gammaherpesvirus 72 (mhv-72) also contained m3 gene with the codon-changing mutation at the position 920 nt converting amino acid (aa) 307 asp (gac) to gly (ggc). the mutation in the m3 protein was localized near chemokin ... | 2008 | 18564895 |
| 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 ... | 2008 | 18648660 |
| 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 ... | 2008 | 18665235 |
| 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 ... | 2008 | 18768196 |
| 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 ... | 2008 | 18768977 |
| 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 ... | 2008 | 18774154 |
| 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 ... | 2008 | 18787698 |
| 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 ... | 2008 | 18818318 |
| persistent gammaherpesvirus replication and dynamic interaction with the host in vivo. | gammaherpesviruses establish life-long persistency inside the host and cause various diseases during their persistent infection. however, the systemic interaction between the virus and host in vivo has not been studied in individual hosts continuously, although such information can be crucial to control the persistent infection of the gammaherpesviruses. for the noninvasive and continuous monitoring of the interaction between gammaherpesvirus and the host, a recombinant murine gammaherpesvirus 6 ... | 2008 | 18842717 |
| lack of heparan sulfate expression in b-cell lines: implications for kaposi's sarcoma-associated herpesvirus and murine gammaherpesvirus 68 infections. | kaposi's sarcoma-associated herpesvirus (kshv) and its murine homolog, murine gammaherpesvirus 68 (mhv68), are lymphotropic viruses that establish latent infection in their host. surprisingly, while b cells are the main viral reservoir in vivo, b-cell lines are poorly permissive to infection by either mhv68 or kshv. here, we report that most b-cell lines express very little to no cell surface heparan sulfate (hs), a glycosaminoglycan that is essential for infection by these viruses. we found tha ... | 2008 | 18842731 |
| 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 ... | 2008 | 18846211 |
| 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 ... | 2008 | 18922872 |
| a repetitive region of gammaherpesvirus genomic dna is a ligand for induction of type i interferon. | innate immune responses against viral infection, especially the induction of type i interferon, are critical for limiting the replication of the virus. although it has been shown that dna can induce type i interferon, to date no natural dna ligand of a virus that induces type i interferon has been described. here we screened the genome of murine gammaherpesvirus 68 with mutations at various genomic locations to map the region of dna that induces type i interferon. a repetitive region termed the ... | 2008 | 18077715 |
| 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 ... | 2008 | 18096403 |
| tlr9 contributes to antiviral immunity during gammaherpesvirus infection. | the human gammaherpesviruses kaposi's sarcoma-associated herpesvirus and ebv cause important infections. as pathogenetic studies of the human infections are restricted, murine gammaherpesvirus 68 serves as a model to study gammaherpesvirus pathogenesis. tlrs are a conserved family of receptors detecting microbial molecular patterns. among the tlrs, tlr9 recognizes unmethylated cpg dna motifs present in bacterial and viral dna. the aim of this study was to assess the role of tlr9 in gammaherpesvi ... | 2008 | 18097045 |
| control of memory cd8+ t cell differentiation by cd80/cd86-cd28 costimulation and restoration by il-2 during the recall response. | memory cd8+ t cell responses have been considered to be independent of cd80/cd86-cd28 costimulation. however, recall responses are often severely blunted in cd28-/- mice. whether this impairment represents a requirement for cd28 costimulation for proper memory cd8+ t cell development or a requirement during the recall response is unknown. furthermore, how cd28 costimulation affects the phenotype and function of memory cd8+ t cells has not been characterized in detail. in this study, we investiga ... | 2008 | 18178855 |
| 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 ... | 2008 | 18191980 |
| 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 ... | 2008 | 17977975 |
| 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) ... | 2008 | 17997402 |
| islet expression of m3 uncovers a key role for chemokines in the development and recruitment of diabetogenic cells in nod mice. | type 1 diabetes is an autoimmune disease characterized by a local inflammatory reaction in and around islets followed by selective destruction of insulin-secreting beta-cells. we tested the hypothesis that chemokines affect different mechanisms responsible for the development of diabetes in nod mice. | 2008 | 18003753 |
| detection and analysis of horizontal gene transfer in herpesvirus. | horizontal gene transfers, where a significant proportion of the coding dna is contributed by external sources, might give rise to extremely dynamic genomes, which brings impact on the ecological and pathogenic characters of the recipient organisms. therefore it is important to computationally discriminate between horizontal transferred genes and normal genes. in this paper, we introduce a novel method for identifying horizontal transferred genes. this method, which relies on a gene's nucleotide ... | 2008 | 17905462 |
| 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 ... | 2009 | 18971285 |
| signaling through toll-like receptors induces murine gammaherpesvirus 68 reactivation in vivo. | murine gammaherpesvirus 68 (mhv68) establishes a lifelong infection in mice and is used as a model pathogen to study the role of viral and host factors in chronic infection. the maintenance of chronic mhv68 infection, at least in some latency reservoirs, appears to be dependent on the capacity of the virus to reactivate from latency in vivo. however, the signals that lead to mhv68 reactivation in vivo are not well characterized. toll-like receptors (tlrs), by recognizing the specific patterns of ... | 2009 | 19019960 |
| alcelaphine herpesvirus-1 open reading frame 57 encodes an immediate-early protein with regulatory function. | alcelaphine herpesvirus-1 (alhv-1) is the causative agent of malignant catarrhal fever, a lymphoproliferative and degenerative disease of large ruminants and ungulate species. the alcelaphine herpesvirus-1 gene product encoded by open reading frame 57 (orf 57) is the positional homologue of the orf 57 of herpes virus saimiri (hvs), kaposi's sarcoma associated herpesvirus (kshv) and murine gammaherpesvirus 68 (mhv 68), the epstein-barr virus bmlf1 gene, the herpes simplex virus (hsv-1) icp 27 and ... | 2009 | 19031004 |
| 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 ... | 2009 | 19073723 |
| 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 ... | 2009 | 19088269 |
| 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 ... | 2009 | 19091863 |
| 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 ... | 2009 | 19109392 |
| 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 ... | 2009 | 19116250 |
| murid herpesvirus-4 induces chronic inflammation of intrahepatic bile ducts in mice deficient in gamma-interferon signalling. | aim: infection of gamma interferon receptor defective mice with murid herpesvirus-4 also known as murine gammaherpesvirus-68 results in multi-organ fibrosis. in this paper we characterise the pathological changes occurring in the liver in this model. methods: standard immunohistochemistry and in situ hybridisation techniques were used to identify the cellular changes and the presence of virus at different times post infection. results: in liver sections from infected gamma interferon receptor de ... | 2009 | 19208039 |
| age-dependent pathogenesis of murine gammaherpesvirus 68 infection of the central nervous system. | gammaherpesvirus infection of the central nervous system (cns) has been linked to various neurological diseases, including meningitis, encephalitis, and multiple sclerosis. however, little is known about the interactions between the virus and the cns in vitro or in vivo. murine gammaherpesvirus 68 (mhv-68 or (gamma)hv-68) is genetically related and biologically similar to human gammaherpesviruses, thereby providing a tractable animal model system in which to study both viral pathogenesis and rep ... | 2009 | 19214440 |
| in vivo importance of heparan sulfate-binding glycoproteins for murid herpesvirus-4 infection. | many herpesviruses bind to heparan sulfate (hs). murid herpesvirus-4 (muhv-4) does so via its envelope glycoproteins gp70 and gh/gl. muhv-4 gp150 further regulates an hs-independent interaction to make that hs-dependent too. cell binding by muhv-4 virions is consequently strongly hs-dependent. gp70 and gh/gl show some in vitro redundancy: an antibody-mediated blockade of hs binding by one is well tolerated, whereas a blockade of both severely impairs infection. in order to understand the importa ... | 2009 | 19218205 |
| rta promoter demethylation and histone acetylation regulation of murine gammaherpesvirus 68 reactivation. | gammaherpesviruses have a common biological characteristic, latency and lytic replication. the balance between these two phases in murine gammaherpesvirus 68 (mhv-68) is controlled by the replication and transcription activator (rta) gene. in this report, we investigated the effect of dna demethylation and histone acetylation on mhv-68 replication. we showed that distinctive methylation patterns were associated with mhv-68 at the rta promoter during latency or lytic replication. treatment of mhv ... | 2009 | 19234612 |
| cd4 t cells mediate killing during persistent gammaherpesvirus 68 infection. | cd4 t cells are critical for the control of gammaherpesvirus persistence, but their direct effector mechanisms of virus control in vivo are still poorly understood. in this study, we use murine gammaherpesvirus 68 (gammahv68) in in vitro and in vivo cytotoxicity assays to show cd4-dependent killing of gammahv68-loaded cells in mice persistently infected with gammahv68. our results underscore the cytotoxic capacity of cd4 t cells during gammahv68 persistence. | 2009 | 19244319 |
| the interaction of the gammaherpesvirus 68 orf73 protein with cellular bet proteins affects the activation of cell cycle promoters. | infection of mice with murine gammaherpesvirus 68 (mhv-68) provides a valuable animal model for gamma-2 herpesvirus (rhadinovirus) infection and pathogenesis. the mhv-68 orf73 protein has been shown to be required for the establishment of viral latency in vivo. this study describes a novel transcriptional activation function of the mhv-68 orf73 protein and identifies the cellular bromodomain containing bet proteins brd2/ring3, brd3/orfx, and brd4 as interaction partners for the mhv-68 orf73 prot ... | 2009 | 19244327 |
| 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, ... | 2009 | 19264603 |
| 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 ... | 2009 | 19264614 |
| 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 ... | 2009 | 19264770 |
| 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 ... | 2009 | 19285330 |
| termination of nf-kappab activity through a gammaherpesvirus protein that assembles an ec5s ubiquitin-ligase. | host colonisation by lymphotropic gammaherpesviruses depends critically on the expansion of viral genomes in germinal centre (gc) b cells. yet, host and virus molecular mechanisms involved in driving such proliferation remain largely unknown. here, we show that the orf73 protein encoded by the murid herpesvirus-4 (muhv-4) inhibits host nuclear factor-kappa b (nf-kappab) transcriptional activity through poly-ubiquitination and subsequent proteasomal-dependent nuclear degradation of the nf-kappab ... | 2009 | 19322197 |
| 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 ... | 2009 | 19386718 |
| 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. | 2009 | 19446726 |
| the m10 locus of murine gammaherpesvirus 68 contributes to both the lytic and the latent phases of infection. | murine gammaherpesvirus 68 (mhv-68) is closely related to epstein-barr virus and kaposi's sarcoma-associated herpesvirus (kshv) and provides a small-animal model to study the pathogenesis of gammaherpesvirus (gammahv) infections. according to the colinear organization of the gammahv genomes, the m10 locus is situated at a position equivalent to the k12 locus of kshv, which codes for proteins of the kaposin family. the m10 locus of mhv-68 has been predicted to code for three overlapping open read ... | 2009 | 19493995 |
| the conserved ul24 family of human alpha, beta and gamma herpesviruses induces cell cycle arrest and inactivation of the cyclinb/cdc2 complex. | the conserved murine gammaherpesvirus 68 orf20 has recently been demonstrated to induce g2 cell cycle arrest followed by apoptosis in human and mouse cells. here, we demonstrate that its homologues ul24 in hsv-1, orf20 in kshv and ul76 in hcmv are also inducers of cell cycle arrest followed by apoptosis in both human and mouse cells. the mechanism of action is similar to that reported for mhv-68 orf20, inactivating the mitotic complex cyclinb/cdc2. | 2009 | 19526192 |
| murine gammaherpesvirus 68 infection of ifngamma unresponsive mice: a small animal model for gammaherpesvirus-associated b-cell lymphoproliferative disease. | gammaherpesviruses are tightly controlled by the host immune response, with gammaherpesvirus-associated malignancies prevalent in immune-suppressed individuals. previously, infection of ifngamma-unresponsive mice with gammaherpesvirus 68 (gammahv68) showed that ifngamma controlled chronic infection, limiting chronic diseases including arteritis and pulmonary fibrosis. here, we show that gammahv68-infected ifngamma receptor-deficient (ifngammar(-/-)) mice uniformly develop angiocentric inflammato ... | 2009 | 19531651 |
| infection with murine gammaherpesvirus 68 exacerbates inflammatory bowel disease in il-10-deficient mice. | we questioned whether infection with murine gammaherpesvirus 68 (hv-68) might exacerbate inflammatory bowel disease using mice deficient in il-10 (il-10-/-) as a model of developing colitis. | 2009 | 19544045 |
| host shutoff is a conserved phenotype of gammaherpesvirus infection and is orchestrated exclusively from the cytoplasm. | lytic infection with the two human gammaherpesviruses, kaposi's sarcoma-associated herpesvirus (kshv) and epstein-barr virus (ebv), leads to significant depletion of the cellular transcriptome. this host shutoff phenotype is driven by the conserved herpesviral alkaline exonuclease, termed sox in kshv and bglf5 in ebv, which in gammaherpesviruses has evolved the genetically separable ability to target cellular mrna. we now show that host shutoff is also a prominent consequence of murine gammaherp ... | 2009 | 19587049 |
| 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- ... | 2009 | 19605591 |
| perturbation of lytic and latent gammaherpesvirus infection in the absence of the inhibitory receptor ceacam1. | control of gammaherpesvirus infections requires a complex, well orchestrated immune response regulated by positive and negative co-signaling molecules. while the impact of co-stimulatory molecules has been addressed in various studies, the role of co-inhibitory receptors has not been tested. the itim-bearing ceacam1 is an inhibitory receptor expressed by a variety of immune cells, including b, t and nk cells. using ceacam1(-/-) mice, we analyzed the in vivo function of ceacam1 during acute and l ... | 2009 | 19621080 |
| 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 ... | 2009 | 19625459 |
| a novel cre recombinase imaging system for tracking lymphotropic virus infection in vivo. | detection, isolation, and identification of individual virus infected cells during long term infection are critical to advance our understanding of mechanisms of pathogenesis for latent/persistent viruses. however, current approaches to study these viruses in vivo have been hampered by low sensitivity and effects of cell-type on expression of viral encoded reporter genes. we have designed a novel cre recombinase (cre)-based murine system to overcome these problems, and thereby enable tracking an ... | 2009 | 19652715 |
| open reading frame 33 of a gammaherpesvirus encodes a tegument protein essential for virion morphogenesis and egress. | tegument is a unique structure of herpesvirus, which surrounds the capsid and interacts with the envelope. morphogenesis of gammaherpesvirus is poorly understood due to lack of efficient lytic replication for epstein-barr virus and kaposi's sarcoma-associated herpesvirus/human herpesvirus 8, which are etiologically associated with several types of human malignancies. murine gammaherpesvirus 68 (mhv-68) is genetically related to the human gammaherpesviruses and presents an excellent model for stu ... | 2009 | 19656880 |
| a gammaherpesvirus ubiquitin-specific protease is involved in the establishment of murine gammaherpesvirus 68 infection. | murine gammaherpesvirus 68 (mhv-68) contains a ubiquitin (ub)-specific cysteine protease (usp) domain embedded within the large tegument protein orf64, as do all other herpesviruses. the biological role of this protease is still unclear, but for the alphaherpesvirus marek's disease virus, its usp is involved in t-cell lymphoma formation. we here study the role of the mhv-68 usp, encoded by orf64. by constructing a mutant virus with a single cysteine-to-alanine replacement in the active site of o ... | 2009 | 19706716 |
| murine gammaherpesvirus 68 infection of gamma interferon-deficient mice on a balb/c background results in acute lethal pneumonia that is dependent on specific viral genes. | gamma interferon (ifn-gamma) is critical for the control of chronic infection with murine gammaherpesvirus 68 (gammahv68). current data indicate that ifn-gamma has a lesser role in the control of acute replication of gammahv68. here, we show that ifn-gamma-deficient mice on the balb/c genetic background poorly control acute viral replication and succumb to early death by acute pneumonia. notably, this acute, lethal pneumonia was dependent not only on the viral dose, but also on specific viral ge ... | 2009 | 19710134 |
| 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 ... | 2009 | 19748577 |
| gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected b lymphocytes. | gammaherpesviruses chronically infect their host and are tightly associated with the development of lymphoproliferative diseases and lymphomas, as well as several other types of cancer. mechanisms involved in maintaining chronic gammaherpesvirus infections are poorly understood and, in particular, little is known about the mechanisms involved in controlling gammaherpesvirus reactivation from latently infected b cells in vivo. recent evidence has linked plasma cell differentiation with reactivati ... | 2009 | 19956661 |
| induction of protective immunity against murine gammaherpesvirus 68 infection in the absence of viral latency. | human gammaherpesviruses, epstein-barr virus, and human herpesvirus 8/kaposi's sarcoma-associated herpesvirus are important pathogens associated with diseases, including lymphomas and other malignancies. murine gammaherpesvirus 68 (mhv-68) is used as an experimental model system to study the host immune control of infection and explore novel vaccine strategies based on latency-deficient live viruses. we studied the properties and the potential of a recombinant mhv-68 (ac-rta) in which the genes ... | 2010 | 20015983 |
| two kinetic patterns of epitope-specific cd8 t-cell responses following murine gammaherpesvirus 68 infection. | murine gammaherpesvirus 68 (gammahv68) provides an important experimental model for understanding mechanisms of immune control of the latent human gammaherpesviruses. antiviral cd8 t cells play a key role throughout three separate phases of the infection: clearance of lytic virus, control of the latency amplification stage, and prevention of reactivation of latently infected cells. previous analyses have shown that t-cell responses to two well-characterized epitopes derived from orf6 and orf61 p ... | 2010 | 20053740 |
| murine gammaherpesvirus 68 has evolved gamma interferon and stat1-repressible promoters for the lytic switch gene 50. | cytokines regulate viral gene expression with important consequences for viral replication and pathogenesis. gamma interferon (ifn-gamma) is a key regulator of chronic murine gammaherpesvirus 68 (gammahv68) infection and a potent inhibitor of gammahv68 reactivation from latency. macrophages are the cell type that is responsive to the ifn-gamma-mediated control of gammahv68 reactivation; however, the molecular mechanism of this ifn-gamma action is undefined. here we report that ifn-gamma inhibits ... | 2010 | 20071569 |
| pathogenesis of a model gammaherpesvirus in a natural host. | murine gammaherpesvirus 68 (mhv-68) infection of laboratory mice (mus musculus) is an established model of gammaherpesvirus pathogenesis. the fact that m. musculus is not a host in the wild prompted us to reassess mhv-68 infection in wood mice (apodemus sylvaticus), a natural host. here, we report significant differences in mhv-68 infection in the two species: (i) following intranasal inoculation, mhv-68 replicated in the lungs of wood mice to levels approximately 3 log units lower than in balb/ ... | 2010 | 20130062 |