Publications

fusion of a viral antigen to invariant chain leads to augmented t-cell immunity and improved protection in gene-gun dna-vaccinated mice.	it has recently been demonstrated that a recombinant replication-deficient human adenovirus 5 (ad5) vector expressing lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp) fused to the p31 invariant (ii) chain confers broad, long-lasting t-cell immunity that completely protects c57bl/6 mice against lethal peripheral challenge. the current study questioned whether the same strategy, i.e. linkage of gp to an ii chain, could be applied to a naked dna vaccine. following gene-gun immunization w ...	2009	19141451
t-cell intrinsic expression of myd88 is required for sustained expansion of the virus-specific cd8+ t-cell population in lcmv-infected mice.	acute infection with lymphocytic choriomeningitis virus (lcmv) normally results in robust clonal expansion of virus-specific cd8(+) t cells, which in turn control the primary infection. however, similar infection of myeloid differentiation factor 88 (myd88)-deficient mice leads to a markedly impaired t-cell response and chronic infection. it has been found previously that impairment of the innate immune response is not sufficient to explain this profound change in outcome. using adoptive transfe ...	2009	19141452
recombination of retrotransposon and exogenous rna virus results in nonretroviral cdna integration.	retroviruses have the potential to acquire host cell-derived genetic material during reverse transcription and can integrate into the genomes of larger, more complex dna viruses. in contrast, rna viruses were believed not to integrate into the host's genome under any circumstances. we found that illegitimate recombination between an exogenous nonretroviral rna virus, lymphocytic choriomeningitis virus, and the endogenous intracisternal a-type particle (iap) retrotransposon occurred and led to re ...	2009	19150848
hepatic microcirculation: a critical but neglected factor for the outcome of viral hepatitis.	more than 500 million people worldwide are persistently infected with hepatitis b virus or hepatitis c virus. although both viruses are poorly cytopathic, persistence of either virus carries a risk of chronic liver inflammation, potentially resulting in liver steatosis, liver cirrhosis, end-stage liver failure or hepatocellular carcinoma. virus-specific t cells are a major determinant of the outcome of hepatitis, as they contribute to the early control of chronic hepatitis viruses, but they also ...	2009	19157626
cd103 is dispensable for anti-viral immunity and autoimmunity in a mouse model of virally-induced autoimmune diabetes.	recent studies suggest a beneficial role for blocking cd103 signaling in preventing islet allograft rejection and thus type 1 diabetes (t1d) in non-obese diabetic (nod) mice. however, antibody blockade approaches generally raise anti-microbial safety issues, necessitating additional studies to address the possible adverse effects of antibody therapy. here we report that cd103 had no significant impact on the development of primary and memory cd8(+) or cd4(+) responses after acute lymphocytic cho ...	2009	19162441
ctl induction by cross-priming is restricted to immunodominant epitopes.	ctl are induced by two pathways, i.e. direct priming, where tumor cells present tumor antigens to naïve specific ctl, and cross-priming, where professional apc cross-present captured tumor antigens to ctl. here, we examined direct priming versus cross-priming after immunizing (h-2(b) x h-2(d)) f1 mice with either h-2(b) or h-2(d) positive tumor cells transfected with the gp or nucleoprotein (np) of lymphocytic choriomeningitis virus (lcmv). cross-priming was observed for the immunodominant epito ...	2009	19189311
cd4 t-cell-mediated heterologous immunity between mycobacteria and poxviruses.	the bacillus calmette-guerin (bcg) strain of mycobacterium bovis is used in many parts of the world as a vaccine against mycobacterium tuberculosis. some epidemiological evidence has suggested that bcg immunization may have unpredicted effects on resistance to other pathogens. we show here in a mouse model that bcg immunization followed by antibiotic treatment to clear the host of the pathogen rendered three strains of mice partially resistant to infection with vaccinia virus (vv) but not to lym ...	2009	19193795
cd8+ t cell responses to a viral escape mutant epitope: active suppression via altered shp-1 activity.	one mechanism viruses use to subvert immune surveillance is through mutation of mhc contact residues of antigenic epitopes that weaken t cell recognition to the point that the immune system is ignorant of the infection. however, in contrast to ignorance, results presented herein demonstrate that intracellular signaling does occur upon stimulation with a lymphocytic choriomeningitis virus-derived escape mutant as demonstrated by the sustained activation of src homology 2 domain-containing protein ...	2009	19201834
requirement of b cells for generating cd4+ t cell memory.	b cells can influence t cell responses by directly presenting ag or by secreting ab that binds to ag to form immunogenic complexes. conflicting evidence suggests that persisting ag-ab complexes propagate long-term t cell memory; yet, other data indicate that memory cells can survive without specific ag or mhc. in this study, the roles of b cells and ag-ab complexes in t cell responses to lymphocytic choriomeningitis virus (lcmv) infection were investigated using b cell-deficient or b cell-compet ...	2009	19201839
no significant ctl cross-priming by dendritic cell-derived exosomes during murine lymphocytic choriomeningitis virus infection.	exosomes are small membrane vesicles of endocytic origin that are secreted by most cells in culture, but are also present in serum. they contain a wide array of protein ligands on their surface, which has led to the hypothesis that they might mediate intercellular communication. indeed, data support that exosomes can transfer ags to dendritic cells (dc), and, interestingly, that these dc can subsequently induce t cell priming or tolerance. we have investigated whether this concept can be expande ...	2009	19201875
generation of recombinant lymphocytic choriomeningitis viruses with trisegmented genomes stably expressing two additional genes of interest.	several arenaviruses cause hemorrhagic fever disease in humans for which no licensed vaccines are available and current therapeutic intervention is limited to the off-label use of the wide-spectrum antiviral ribavirin. however, the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) has proven to be a rosetta stone for the investigation of virus-host interactions. arenaviruses have a bisegmented negative-strand rna genome. the s segment encodes for the virus nucleoprotein and glycopr ...	2009	19208813
impact of epitope escape on pd-1 expression and cd8 t-cell exhaustion during chronic infection.	during some persistent viral infections, virus-specific t-cell responses wane due to the antigen-specific deletion or functional inactivation (i.e., exhaustion) of responding cd8 t cells. t-cell exhaustion often correlates with high viral load and is associated with the expression of the inhibitory receptor pd-1. in other infections, functional t cells are observed despite high levels of pathogen persistence. the reasons for these different t-cell fates during chronic viral infections are not cl ...	2009	19211743
gene expression in primate liver during viral hemorrhagic fever.	rhesus macaques infected with lymphocytic choriomeningitis virus (lcmv) provide a model for human lassa fever. disease begins with flu-like symptoms and progresses rapidly with fatal consequences. previously, we profiled the blood transcriptome of lcmv-infected monkeys (m. djavani et al j. virol. 2007) showing distinct pre-viremic and viremic stages that discriminated virulent from benign infections. in the present study, changes in liver gene expression from macaques infected with virulent lcmv ...	2009	19216742
nkt cell-plasmacytoid dendritic cell cooperation via ox40 controls viral infection in a tissue-specific manner.	invariant natural killer t (inkt) cells promote immune responses to various pathogens, but exactly how inkt cells control antiviral responses is unclear. here, we showed that inkt cells induced tissue-specific antiviral effects in mice infected by lymphocytic choriomeningitis virus (lcmv). indeed, inkt cells inhibited viral replication in the pancreas and liver but not in the spleen. in the pancreas, inkt cells expressed the ox40 molecule and promoted type i interferon (ifn) production by plasma ...	2009	19217323
defective homing and impaired induction of cytotoxic t cells by bcr/abl-expressing dendritic cells.	chronic myelogenous leukemia (cml) is a malignant myeloproliferative disease arising from a hematopoietic stem cell expressing the bcr/abl fusion protein. leukemic and dendritic cells (dcs) develop from the same transformed hematopoietic progenitors. how bcr/abl interferes with the immunoregulatory function of dcs in vivo is unknown. we analyzed the function of bcr/abl-expressing dcs in a retroviral-induced murine cml model using the glycoprotein of lymphocytic choriomeningitis virus as a model ...	2009	19252140
a case of congenital lymphocytic choriomeningitis virus (lcmv) infection revealed by hydrops fetalis.		2009	19253314
receptor binding and cell entry of old world arenaviruses reveal novel aspects of virus-host interaction.	ten years ago, the first cellular receptor for the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) and the highly pathogenic lassa virus (lasv) was identified as alpha-dystroglycan (alpha-dg), a versatile receptor for proteins of the extracellular matrix (ecm). biochemical analysis of the interaction of alpha-dg with arenaviruses and ecm proteins revealed a strikingly similar mechanism of receptor recognition that critically depends on specific sugar modification on alpha-dg invo ...	2009	19324387
visualizing antigen-specific and infected cells in situ predicts outcomes in early viral infection.	in the early stages of viral infection, outcomes depend on a race between expansion of infection and the immune response generated to contain it. we combined in situ tetramer staining with in situ hybridization to visualize, map, and quantify relationships between immune effector cells and their targets in tissues. in simian immunodeficiency virus infections in macaques and lymphocytic choriomeningitis virus infections in mice, the magnitude and timing of the establishment of an excess of effect ...	2009	19325114
impaired antibody response causes persistence of prototypic t cell-contained virus.	cd8 t cells are recognized key players in control of persistent virus infections, but increasing evidence suggests that assistance from other immune mediators is also needed. here, we investigated whether specific antibody responses contribute to control of lymphocytic choriomeningitis virus (lcmv), a prototypic mouse model of systemic persistent infection. mice expressing transgenic b cell receptors of lcmv-unrelated specificity, and mice unable to produce soluble immunoglobulin m (igm) exhibit ...	2009	19355789
transcription factor foxo3 controls the magnitude of t cell immune responses by modulating the function of dendritic cells.	foxo transcription factors regulate cell cycle progression, cell survival and dna-repair pathways. here we demonstrate that deficiency in foxo3 resulted in greater expansion of t cell populations after viral infection. this exaggerated expansion was not t cell intrinsic. instead, it was caused by the enhanced capacity of foxo3-deficient dendritic cells to sustain t cell viability by producing more interleukin 6. stimulation of dendritic cells mediated by the coinhibitory molecule ctla-4 induced ...	2009	19363483
programmed death-1 as a factor in immune exhaustion and activation in hiv infection.	the aim of this article is to understand the dual role of programmed death-1 (pd-1) as a physiological negative regulator of t cell activation and a mediator of t cell exhaustion in hiv infection.	2008	19372991
[toscana virus, west nile virus and lymphochoriomeningitis virus as causing agents of aseptic meningitis in spain].	cases of aseptic meningitis (am) are mostly due to enterovirus (ev), herpesvirus, and mumps virus (mv). an important number of cases remains without an etiologic diagnosis.	2009	19375119
mice deficient in stem cell antigen-1 (sca1, ly-6a/e) develop normal primary and memory cd4+ and cd8+ t-cell responses to virus infection.	stem cell antigen-1 (sca1, ly-6a/e) is a well-established marker of murine hematopoietic stem cells, and also is expressed on memory t cells. it has been suggested that the functional maintenance of t-cell memory requires the expression of sca1 on a specialized population of memory t cells termed "memory stem cells". here, we evaluate the requirement for sca1 in the primary t-cell response to virus infection, and in the establishment and maintenance of t-cell memory. we find that sca1 expression ...	2009	19384870
adjuvant il-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies.	identifying key factors that enhance immune responses is crucial for manipulating immunity to tumors. we show that after a vaccine-induced immune response, adjuvant interleukin-7 (il-7) improves antitumor responses and survival in an animal model. the improved immune response is associated with increased il-6 production and augmented t helper type 17 cell differentiation. furthermore, il-7 modulates the expression of two ubiquitin ligases: casitas b-lineage lymphoma b (cbl-b), a negative regulat ...	2009	19396174
programmed death 1 signaling on chronic myeloid leukemia-specific t cells results in t-cell exhaustion and disease progression.	chronic myeloid leukemia (cml) is a malignant myeloproliferative disease with a characteristic chronic phase (cp) of several years before progression to blast crisis (bc). the immune system may contribute to disease control in cml. we analyzed leukemia-specific immune responses in cpcml and bccml in a retroviral-induced murine cml model. in the presence of cpcml and bccml expressing the glycoprotein of lymphocytic choriomeningitis virus as a model leukemia antigen, leukemia-specific cytotoxic t ...	2009	19420358
il-21 is required to control chronic viral infection.	cd4+ and cd8+ t cell functions are rapidly aborted during chronic infection, preventing viral clearance. cd4+ t cell help is required throughout chronic infection so as to sustain cd8+ t cell responses; however, the necessary factor(s) provided by cd4+ t cells are currently unknown. using a mouse model of chronic viral infection, we demonstrated that interleukin-21 (il-21) is an essential component of cd4+ t cell help. in the absence of il-21 signaling, despite elevated cd4+ t cell responses, cd ...	2009	19423777
high antigen levels are the cause of t cell exhaustion during chronic viral infection.	many persistent viral infections induce dysfunctional t cell responses. although a negative correlation exists between viral load and t cell responses during chronic infection, it is not known whether high antigen levels are the cause or just the consequence of t cell exhaustion. furthermore, it is unclear what role antigen presentation by bone-marrow (bm) derived versus infected parenchymal cells has on t cell exhaustion. to address these issues, we examined the influence of antigen presentatio ...	2009	19433785
a vital role for interleukin-21 in the control of a chronic viral infection.	understanding the factors that regulate the induction, quality, and longevity of antiviral t cell responses is essential for devising rational strategies to prevent or combat infections. in this study, we show that interleukin-21 (il-21), likely produced by cd4+ t cells, directly influences the generation of polyfunctional cd8+ t cells and that the number of cd4+ t cells that produce il-21 differs markedly between acute and chronic infections. il-21 regulates the development of cd8+ t cell exhau ...	2009	19443735
chronic antigen stimulation alone is sufficient to drive cd8+ t cell exhaustion.	the failure of cd8(+) t cells to respond to chronic infection has been termed "exhaustion" and describes the condition in which cd8(+) t cells exhibit reduced differentiation, proliferation, and effector function. cd8(+) t cell exhaustion has been extensively studied in the murine model of chronic infection, lymphocytic choriomeningitis virus (lcmv). although lcmv-based studies have yielded many interesting findings, they have not allowed for discrimination between the roles of cytokine- and ag- ...	2009	19454664
multiple mechanisms contribute to impairment of type 1 interferon production during chronic lymphocytic choriomeningitis virus infection of mice.	type 1 ifns, innate cytokines with important effector and immunomodulatory properties, are rapidly induced in the acute phase of many virus infections; however, this is generally a transient response that is not sustained during virus persistence. to gain insight into mechanisms that can contribute to down-regulation of type 1 ifn production during virus persistence, we analyzed type 1 ifn production during acute and chronic lymphocytic choriomeningitis virus (lcmv) infection. high-level type 1 ...	2009	19454715
antigens expressed by myelinating glia cells induce peripheral cross-tolerance of endogenous cd8+ t cells.	auto-reactivity of t cells is largely prevented by central and peripheral tolerance. nevertheless, immunization with certain self-antigens emulsified in cfa induces autoimmunity in rodents, suggesting that tolerance to some self-antigens is not robust. to investigate the fate of nervous system-specific cd8(+) t cells, which only recently came up as being important contributors for ms pathogenesis, we developed a mouse model that allows inducible expression of lymphocytic choriomeningitis virus-d ...	2009	19462379
il-21r on t cells is critical for sustained functionality and control of chronic viral infection.	chronic viral infection is often associated with the dysfunction of virus-specific t cells. our studies using il21r-deficient (il21r-/-) mice now suggest that interleukin-21 (il-21) is critical for the long-term maintenance and functionality of cd8+ t cells and the control of chronic lymphocytic choriomeningitis virus infection in mice. cell-autonomous il-21 receptor (il-21r)-dependent signaling by cd8+ t cells was required for sustained cell proliferation and cytokine production during chronic ...	2009	19478140
immunoregulatory mechanisms triggered by viral infections protect from type 1 diabetes in mice.	type 1 diabetes (t1d) is an autoimmune disease that is caused by the destruction of insulin-producing beta cells. viral infections induce immune responses that can damage beta cells and promote t1d or on the other hand prevent the development of the disease. however, the opposing roles of viral infections in t1d are not understood mechanistically. we report here that viruses that do not inflict damage on beta cells provided protection from t1d by triggering immunoregulatory mechanisms. infection ...	2009	19478458
the nucleoprotein of lymphocytic choriomeningitis virus facilitates spread of persistent infection through stabilization of the keratin network.	lymphocytic choriomeningitis virus (lcmv) is a prototypic arenavirus containing a bisegmented single-stranded rna genome with an ambisense coding strategy. mx is a noncytolytic lcmv strain with an in vitro host range restricted to only few cell lines. mx lcmv spreads via cell-cell contacts and causes persistent infection with high production of viral nucleoprotein (np). using a proteomic approach, we identified keratin 1 (k1), an intermediate filament network component, as a binding partner of t ...	2009	19494018
response and recovery in the plasma metabolome tracks the acute lcmv-induced immune response.	lymphocytic choriomeningitis virus (lcmv) infection of mice is noncytopathic, producing well-characterized changes reflecting the host immune response. untargeted metabolomics using mass spectrometry identified endogenous small molecule changes in blood from mice inoculated with lcmv, sampled at days 1, 3, 7, and 14 post infection. these time points correspond to well characterized events during acute lcmv infection and the immune response. diverse pathways were altered, including tca cycle inte ...	2009	19496611
can childhood viral infection protect from type 1 diabetes?	while many candidate type 1 diabetes (t1d) susceptibility genes have been identified, evidence suggests that environmental stimuli, such as viral infections, may also be involved in t1d pathogenesis. however, how viral infections may prevent or trigger the diabetogenic process remains unclear. in this issue of the jci, filippi et al. show that infection of nod mice with coxsackie virus b3 or lymphocytic choriomeningitis virus, neither of which directly destroys insulin-secreting pancreatic beta ...	2009	19504721
gamma interferon signaling in macrophage lineage cells regulates central nervous system inflammation and chemokine production.	intracranial (i.c.) infection of mice with lymphocytic choriomeningitis virus (lcmv) results in anorexic weight loss, mediated by t cells and gamma interferon (ifn-gamma). here, we assessed the role of cd4(+) t cells and ifn-gamma on immune cell recruitment and proinflammatory cytokine/chemokine production in the central nervous system (cns) after i.c. lcmv infection. we found that t-cell-depleted mice had decreased recruitment of hematopoietic cells to the cns and diminished levels of ifn-gamma ...	2009	19515766
inflammation on the mind: visualizing immunity in the central nervous system.	the central nervous system (cns) is a remarkably complex structure that utilizes electrochemical signaling to coordinate activities throughout the entire body. because the nervous system contains nonreplicative cells, it is postulated that, through evolutionary pressures, this compartment has acquired specialized mechanisms to limit damage. one potential source of damage comes from our immune system, which has the capacity to survey the cns and periphery for the presence of foreign material. the ...	2009	19521688
a selective inhibitor of the immunoproteasome subunit lmp7 blocks cytokine production and attenuates progression of experimental arthritis.	the immunoproteasome, a distinct class of proteasome found predominantly in monocytes and lymphocytes, is known to shape the antigenic repertoire presented on class i major histocompatibility complexes (mhc-i). however, a specific role for the immunoproteasome in regulating other facets of immune responses has not been established. we describe here the characterization of pr-957, a selective inhibitor of low-molecular mass polypeptide-7 (lmp7, encoded by psmb8), the chymotrypsin-like subunit of ...	2009	19525961
acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary t lymphocytes.	granule-mediated cytotoxicity is the main effector mechanism of cytotoxic cd8+ t cells. we report that cd8+ t cells from acid sphingomyelinase (asmase)-deficient (asmase-ko) mice are defective in exocytosis of cytolytic effector molecules; this defect resulted in attenuated cytotoxic activity of asmase-ko cd8+ t cells and delayed elimination of lymphocytic choriomeningitis virus from asmase-ko mice. cytolytic granules of asmase-ko and wild-type cd8+ t cells were equally loaded with granzymes and ...	2009	19525969
cd8+ t cell immunodominance shifts during the early stages of acute lcmv infection independently from functional avidity maturation.	virus-specific t cell responses are often directed to a small subset of possible epitopes and their relative magnitude defines their hierarchy. we determined the size and functional avidity of 4 representative peptide-specific cd8(+) t cell populations in c57bl/6 mice at different time points after lymphocytic choriomeningitis virus (lcmv) infection. we found that the frequency of different peptide-specific t cell populations in the spleen changed independently over the first 8 days after infect ...	2009	19539966
mtor regulates memory cd8 t-cell differentiation.	memory cd8 t cells are a critical component of protective immunity, and inducing effective memory t-cell responses is a major goal of vaccines against chronic infections and tumours. considerable effort has gone into designing vaccine regimens that will increase the magnitude of the memory response, but there has been minimal emphasis on developing strategies to improve the functional qualities of memory t cells. here we show that mtor (mammalian target of rapamycin, also known as frap1) is a ma ...	2009	19543266
effector t-cell differentiation during viral and bacterial infections: role of direct il-12 signals for cell fate decision of cd8(+) t cells.	to study the role of il-12 as a third signal for t-cell activation and differentiation in vivo, direct il-12 signaling to cd8(+) t cells was analyzed in bacterial and viral infections using the p14 t-cell adoptive transfer model with cd8(+) t cells that lack the il-12 receptor. results indicate that cd8(+) t cells deficient in il-12 signaling were impaired in clonal expansion after listeria monocytogenes infection but not after infection with lymphocytic choriomeningitis virus, vaccinia virus or ...	2009	19548244
therapeutic memory t cells require costimulation for effective clearance of a persistent viral infection.	persistent viral infections are a major health concern worldwide. during persistent infection, overwhelming viral replication and the rapid loss of antiviral t-cell function can prevent immune-mediated clearance of the infection, and therapies to reanimate the immune response and purge persistent viruses have been largely unsuccessful. adoptive immunotherapy using memory t cells is a highly successful therapeutic approach to eradicate a persistent viral infection. understanding precisely how the ...	2009	19553326
meningitis in a college student in connecticut, 2007.	the authors describe a case of aseptic meningitis in a college student that was ultimately attributed to infection with lymphocytic choriomeningitis virus (lcmv). the authors also provide a review of lcmv infection, epidemiology, and public health implications. providers should be aware of lcmv as a cause of meningitis in college students, especially those with a history of rodent exposure.	2009	19592348
cell-intrinsic transforming growth factor-beta signaling mediates virus-specific cd8+ t cell deletion and viral persistence in vivo.	although deficient cd8(+) t cell responses have long been associated with chronic viral infections, the underlying mechanisms are still unclear. here we report that sustained transforming growth factor-beta (tgf-beta) expression and phosphorylation of its signaling mediator, smad-2, were distinctive features of virus-specific cd8(+) t cells during chronic versus acute viral infections in vivo. the result was tgf-beta-dependent apoptosis of virus-specific cd8(+) t cells that related to upregulati ...	2009	19604493
the magnitude of cd4+ t cell recall responses is controlled by the duration of the secondary stimulus.	the parameters controlling the generation of robust cd4(+) t cell recall responses remain poorly defined. in this study, we compare recall responses by cd4(+) and cd8(+) memory t cells following rechallenge. homologous rechallenge of mice immune to either lymphocytic choriomeningitis virus or listeria monocytogenes results in robust cd8(+) t cell recall responses but poor boosting of cd4(+) t cell recall responses in the same host. in contrast, heterologous rechallenge with a pathogen sharing on ...	2009	19605694
bcl6 and blimp-1 are reciprocal and antagonistic regulators of t follicular helper cell differentiation.	effective b cell-mediated immunity and antibody responses often require help from cd4+ t cells. it is thought that a distinct cd4+ effector t cell subset, called t follicular helper cells (t(fh)), provides this help; however, the molecular requirements for t(fh) differentiation are unknown. we found that expression of the transcription factor bcl6 in cd4+ t cells is both necessary and sufficient for in vivo t(fh) differentiation and t cell help to b cells in mice. in contrast, the transcription ...	2009	19608860
remission of invasive, cancer stem-like glioblastoma xenografts using lentiviral vector-mediated suicide gene therapy.	glioblastoma is the most frequent and most malignant primary brain tumor with a poor prognosis. the translation of therapeutic strategies for glioblastoma from the experimental phase into the clinic has been limited by insufficient animal models, which lack important features of human tumors. lentiviral gene therapy is an attractive therapeutic option for human glioblastoma, which we validated in a clinically relevant animal model.	2009	19617915
spatial and temporal dynamics of lymphocytic choriomeningitis virus in wild rodents, northern italy.	we determined the prevalence of infection with lymphocytic choriomeningitis virus (lcmv) among small mammals in northern italy and analyzed long-term dynamics of lcmv in a rodent population in the province of trento. lcmv is circulating among the most widespread and common wild rodent species in this area (apodemus flavicollis, myodes glareolus, and microtus arvalis); overall prevalence is 6.8%. during 2000-2006, intensive monitoring of lcmv in a population of yellow-necked mice (a. flavicollis) ...	2009	19624914
basal lamina strengthens cell membrane integrity via the laminin g domain-binding motif of alpha-dystroglycan.	skeletal muscle basal lamina is linked to the sarcolemma through transmembrane receptors, including integrins and dystroglycan. the function of dystroglycan relies critically on posttranslational glycosylation, a common target shared by a genetically heterogeneous group of muscular dystrophies characterized by alpha-dystroglycan hypoglycosylation. here we show that both dystroglycan and integrin alpha7 contribute to force-production of muscles, but that only disruption of dystroglycan causes det ...	2009	19633189
vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent cd4(+) t-cell-independent cd8(+) t-cell-mediated tumor control.	antigen-specific immunotherapy is an attractive strategy for cancer control. in the context of antiviral vaccines, adenoviral vectors have emerged as a favorable means for immunization. therefore, we chose a strategy combining use of these vectors with another successful approach, namely linkage of the vaccine antigen to invariant chain (ii). to evaluate this strategy we used a mouse model, in which an immunodominant epitope (gp33) of the lcmv glycoprotein (gp) represents the tumor-associated ne ...	2009	19637230
microbial contaminations of laboratory mice and rats in taiwan from 2004 to 2007.	limited data are available on the pathogen status of contemporary rodent colonies in taiwan. here we summarized the rodent pathogen diagnostic records of the taiwan national laboratory animal center during a 4-y period that representing approximately 10% of the rodent colonies in taiwan. demand for pathogen diagnostic service increased continuously from 2004 to 2007, with a 20% increase each year. in 2007, more than 20% of the mouse colonies were positive for mouse parvovirus, mouse hepatitis vi ...	2009	19653946
transcriptional repressor blimp-1 promotes cd8(+) t cell terminal differentiation and represses the acquisition of central memory t cell properties.	during acute infections, a small population of effector cd8(+) t cells evades terminal differentiation and survives as long-lived memory t cells. we demonstrate that the transcriptional repressor blimp-1 enhanced the formation of terminally differentiated cd8(+) t cells during lymphocytic choriomeningitis virus (lcmv) infection, and blimp-1 deficiency promoted the acquisition of memory cell properties by effector cells. blimp-1 expression was preferentially increased in terminally differentiated ...	2009	19664941
a role for the transcriptional repressor blimp-1 in cd8(+) t cell exhaustion during chronic viral infection.	t cell exhaustion is common during chronic infections and can prevent optimal immunity. although recent studies have demonstrated the importance of inhibitory receptors and other pathways in t cell exhaustion, the underlying transcriptional mechanisms are unknown. here, we define a role for the transcription factor blimp-1 in cd8(+) t cell exhaustion during chronic viral infection. blimp-1 repressed key aspects of normal memory cd8(+) t cell differentiation and promoted high expression of inhibi ...	2009	19664943
obstetrician/gynecologists' knowledge, attitudes, and practices regarding prevention of infections in pregnancy.	maternal infection during pregnancy is a well-recognized cause of birth defects and developmental disabilities, as well as an important contributor to other adverse pregnancy outcomes. the objective of the present survey was to gain information about the knowledge, attitudes, and practices of obstetrician/gynecologists regarding prevention of infections during pregnancy.	2009	19670963
the hepatitis c virus non-structural ns5a protein impairs both the innate and adaptive hepatic immune response in vivo.	the role of hepatitis c virus (hcv) protein non-structural (ns) 5a in hcv-associated pathogenesis is still enigmatic. to investigate the in vivo role of ns5a for viral persistence and virus-associated pathogenesis a transgenic (tg) mouse model was established. mice with liver-targeted ns5a transgene expression were generated using the albumin promoter. alterations in the hepatic immune response were determined by western blot, infection by lymphocytic choriomeningitis virus (lcmv), and using tra ...	2009	19674968
highly efficient antiviral cd8+ t-cell induction by peptides coupled to the surfaces of liposomes.	in previous studies, we have demonstrated that liposomes with differential lipid components display differential adjuvant effects when antigens (ags) are chemically coupled to their surfaces. when ovalbumin was coupled to liposomes made by using unsaturated fatty acids, it was found to be presented not only to cd4(+) t cells but also to cd8(+) t cells and induced cytotoxic t lymphocytes (ctls) which effectively eradicated the tumor from mice. in this study, we coupled liposomes to immunodominant ...	2009	19675224
blimp hovers over t cell immunity.	the functions of t lymphocytes are regulated by transcription factors controlling gene expression. three studies in this issue of immunity (kallies et al., 2009; rutishauser et al., 2009; shin et al., 2009) indicate that the transcriptional repressor blimp-1 promotes the development of short-lived effector cells and regulates clonal exhaustion.	2009	19699168
identification of amino acid residues critical for the anti-interferon activity of the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus.	lymphocytic choriomeningitis virus (lcvm) nucleoprotein (np) counteracts the host type i interferon (ifn) response by inhibiting activation of the ifn regulatory factor 3 (irf3). in this study, we have mapped the regions and specific amino acid residues within np involved in its anti-ifn activity. we identified a region spanning residues 382 to 386 as playing a critical role in the ifn-counteracting activity of np. alanine substitutions at several positions within this region resulted in np muta ...	2009	19710144
viral triggers for autoimmunity: is the 'glass of molecular mimicry' half full or half empty?	in this review we want to consider some of the requirements for autoimmune disease to develop and how this may be reproduced in animal models. besides a genetic predisposition, environmental triggering factors seem to play a central role in the etiology of many autoimmune diseases. in theory, a structural similarity or identity between the host and an invading pathogen might cause the immune system of the host to react not only to the pathogen but also to self-components. however, in order for s ...	2010	19716269
persistent viral infection elevates central nervous system mhc class i through chronic production of interferons.	persistence of even the stealthiest viruses can perturb immune function either to the benefit or detriment of the host. lymphocytic choriomeningitis virus (lcmv) establishes lifelong, systemic persistence when introduced in utero or at birth. despite a highly evolved host-pathogen relationship, lcmv cannot escape detection by the innate immune system, which results in chronic stimulation of the type 1 ifn pathway in adult carrier mice. in this study we demonstrate that ifn-beta is chronically up ...	2009	19717517
circulating natural killer and gammadelta t cells decrease soon after infection of rhesus macaques with lymphocytic choriomeningitis virus.	rhesus macaques infected with the we strain of lymphocytic choriomeningitis virus (lcmv-we) serve as a model for human infection with lassa fever virus. to identify the earliest events of acute infection, rhesus macaques were monitored immediately after lethal infection for changes in peripheral blood mononuclear cells (pbmcs). changes in cd3, cd4, cd8 and cd20 subsets did not vary outside the normal fluctuations of these blood cell populations; however, natural killer (nk) and gammadelta t cell ...	2009	19722081
activation of transgene-specific t cells following lentivirus-mediated gene delivery to mouse lung.	integrating lentiviral vectors based on the human immunodeficiency virus type-1 (hiv-1) can transduce quiescent cells, which in lung account for almost 95% of the epithelial cell population. pseudotyping lentiviral vectors with the envelope glycoprotein from the ebola zaire virus, the lymphocytic choriomeningitis virus (lcmv), the mokola virus, and the vesicular stomatitis virus (vsv-g) resulted in transduction of mouse alveolar epithelium, but gene expression in the lung of c57bl/6 and balb/c m ...	2010	19724265
epitope specificity and relative clonal abundance do not affect cd8 differentiation patterns during lymphocytic choriomeningitis virus infection.	to evaluate the impact of immunodominance on cd8 t-cell properties, we compared the functional properties of dominant and subdominant populations in the response to lymphocytic choriomeningitis virus (lcmv). to improve functional discrimination, in addition to the usual tests of phenotype and function, we used a sensitive technique that allows the screening of all cd8 effector genes simultaneously in single cells. surprisingly, these methods failed to reveal a major impact of clonal dominance in ...	2009	19726518
thpok derepression is required for robust cd8 t cell responses to viral infection.	in the thymus, the transcription factor thpok is essential for the development of the cd4 helper t cell lineage, whereas active repression of thpok is critical for the development of the cd8 cytotoxic t cell lineage. thpok gene silencing is thought to be irreversible in peripheral cd8 t cells. we noticed that thpok repression is readily abrogated upon in vitro tcr stimulation of peripheral cd8 t cells. this observation prompted us to investigate a role for thpok in the cd8 t cell response to an ...	2009	19734230
t-cell reconstitution without t-cell immunopathology in two models of t-cell-mediated tissue destruction.	antigen-specific t cells play a pivotal role in adaptive immune responses. however, they also contribute to the progression of a variety of diseases including autoimmune disorders, graft rejection and graft-versus-host disease (gvhd). non-specific immune-ablation treatments compromise the ability of the host to respond to infection, whereas the selective removal of epitope-specific t cells could theoretically ameliorate t-cell-mediated pathology while preserving the rest of the host immune funct ...	2009	19740373
molecular and cell biology of the prototypic arenavirus lcmv: implications for understanding and combating hemorrhagic fever arenaviruses.	arenaviruses merit interest as experimental model systems to study virus-host interactions and as clinically important human pathogens. several arenaviruses, chiefly lassa virus (lasv), cause hemorrhagic fever (hf) in humans. in addition, evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is a neglected human pathogen. moreover, arenaviruses pose a biodefense threat. no licensed arenavirus vaccines are available, and current therapy ...	2009	19751403
bone marrow as an alternative site for islet transplantation.	the liver is the current site for pancreatic islet transplantation, but has many drawbacks due to immunologic and nonimmunologic factors. we asked whether pancreatic islets could be engrafted in the bone marrow (bm), an easily accessible and widely distributed transplant site that may lack the limitations seen in the liver. syngeneic islets engrafted efficiently in the bm of c57bl/6 mice rendered diabetic by streptozocin treatment. for more than 1 year after transplantation, these animals showed ...	2009	19773545
interleukin-1 mediates long-term hippocampal dentate granule cell loss following postnatal viral infection.	viral infections of the developing cns can cause long-term neuropathological sequela through undefined mechanisms. proinflammatory cytokines such as il-1beta have gained attention in mediating neurodegeneration in corticohippocampal structures due to a variety of insults in adults, though there is less information on the developing brain. little is known concerning the spatial-temporal pattern of il-1beta induction in the developing hippocampus following live virus infection, and there are few s ...	2010	19774496
a little 'help' from il-21 during persistent viral infection.	anti-viral cd4(+) t cells are required to orchestrate and sustain the activities of the adaptive immune system during a persistent viral infection. three recent studies suggest that cd4(+) t cells accomplish this in part through the release of il-21.	2010	19797314
high frequencies of virus-specific cd8+ t-cell precursors.	a productive cd8(+) t-cell response to a viral infection requires rapid division and proliferation of virus-specific cd8(+) t cells. tetramer-based enrichment assays have recently given estimates of the numbers of peptide-major histocompatibility complex-specific cd8(+) t cells in naïve mice, but precursor frequencies for entire viruses have been examined only by using in vitro limiting-dilution assays (ldas). to examine cd8(+) t-cell precursor frequencies for whole viruses, we developed an in v ...	2009	19812167
lymphocytic choriomeningitis virus-induced mortality in mice is triggered by edema and brain herniation.	although much is known about lymphocytic choriomeningitis virus (lcmv) infection and the subsequent immune response in its natural murine host, some crucial aspects of lcmv-mediated pathogenesis remain undefined, including the underlying basis of the characteristic central nervous system disease that occurs following intracerebral (i.c.) challenge. we show that the classic seizures and paresis that occur following i.c. infection of adult, immunocompetent mice with lcmv are accompanied by anatomi ...	2010	19828618
analysis of the role of tripeptidyl peptidase ii in mhc class i antigen presentation in vivo.	previous experiments using enzyme inhibitors and rna interference in cell lysates and cultured cells have suggested that tripeptidyl peptidase ii (tppii) plays a role in creating and destroying mhc class i-presented peptides. however, its precise contribution to these processes has been controversial. to elucidate the importance of tppii in mhc class i ag presentation, we analyzed tppii-deficient gene-trapped mice and cell lines from these animals. in these mice, the expression level of tppii wa ...	2009	19841172
the proteasome inhibitor bortezomib enhances the susceptibility to viral infection.	the proteasome, a multicatalytic protease, is responsible for the generation of most mhc class i ligands. bortezomib, a proteasome inhibitor, is clinically approved for treatment of multiple myeloma and mantle cell myeloma. in the present study, we investigated the effect of bortezomib on viral infection. infection of bortezomib-treated mice with the lymphocytic choriomeningitis virus (lcmv) led to a decreased cytotoxic t cell response to several lcmv-derived cd8(+) t cell epitopes. bortezomib t ...	2009	19841190
viral infection induces de novo lesions of coronary allograft vasculopathy through a natural killer cell-dependent pathway.	viral infections including those due to cytomegalovirus have been associated with accelerated cardiac allograft vasculopathy (cav) in clinical trials and some animal models. evidence demonstrating a direct causal relationship between such infections and de novo formation of coronary vascular lesions is lacking. heterotopic murine cardiac transplants were performed in a parental to f1 combination in animals lacking both t- and b-lymphocytes (rag(-/-)). coronary vasculopathy developed almost exclu ...	2009	19843029
targeting the proteolytic processing of the viral glycoprotein precursor is a promising novel antiviral strategy against arenaviruses.	a crucial step in the arenavirus life cycle is the biosynthesis of the viral envelope glycoprotein (gp) responsible for virus attachment and entry. processing of the gp precursor (gpc) by the cellular proprotein convertase site 1 protease (s1p), also known as subtilisin-kexin-isozyme 1 (ski-1), is crucial for cell-to-cell propagation of infection and production of infectious virus. here, we sought to evaluate arenavirus gpc processing by s1p as a target for antiviral therapy using a recently dev ...	2010	19846507
resistance to vaccinia virus is less dependent on tnf under conditions of heterologous immunity.	tnf has been shown to be important for controlling many pathogens. here, we directly demonstrate using wild-type tnf(-/-) and tnfr1(-/-) mice that tnf does play a role in protection against vaccinia virus (vv) infection in naive mice. since vv replication is also partially controlled in lymphocytic choriomeningitis virus (lcmv)-immune c57bl/6j mice through the process of heterologous immunity, we questioned whether tnf was required in mediating this protection. vv-infected lcmv-immune mice that ...	2009	19846867
independent lineage of lymphocytic choriomeningitis virus in wood mice (apodemus sylvaticus), spain.	to clarify the presence of lymphocytic choriomeningitis virus (lcmv) in spain, we examined blood and tissue specimens from 866 small mammals. lcmv rna was detected in 3 of 694 wood mice (apodemus sylvaticus). phylogenetic analyses suggest that the strains constitute a new evolutionary lineage. lcmv antibodies were detected in 4 of 10 rodent species tested.	2009	19861074
persistence of lymphocytic choriomeningitis virus in immune animals and its relation to immunity.	in some apparently healthy mice the virus of lymphocytic choriomeningitis persisted for a considerable period of time after recovery, in the blood, urine, and nasal secretions, while in other mice it soon became undemonstrable. it is possible that the persistence of the virus is due to lesions in the lungs, liver, and kidneys. the immunity to lymphocytic choriomeningitis in mice does not seem to depend upon the presence of virus in the blood and the organs tested. no antivirus was detected in se ...	1936	19870509
immunization of guinea pigs with a modified strain of lymphocytic choriomeningitis virus.	a strain of choriomeningitis virus which was highly virulent for guinea pigs, as isolated from a naturally infected white mouse, has been markedly attenuated for guinea pigs by serial intracerebral passage through white mice. the change of virulence occurred before the 8th serial passage. the modified virus as a rule produces fever in guinea pigs but no other symptoms, and the infection is followed by a very solid immunity. parallel passages of the same strain through guinea pigs have maintained ...	1937	19870665
characteristics of a strain of lymphocytic choriomeningitis virus encountered as a contaminant in tissue cultures of rabies virus.	a strain of lymphocytic choriomeningitis virus has been encountered, which grows readily in mouse embryo, serum, tyrode culture media. its origin is not definitely known but appears to be either the mouse brain tissue or, more probably, the monkey serum. this strain gives clear cut results on filtration tests through elford membranes, establishing the size of the virus, according to formula, as 33 to 50 mmicro. the strain shows a high and uniform virulence in w-swiss mice. this appears to be due ...	1940	19870952
studies in rodent poliomyelitis : i. further experiments with the murine strain of sk poliomyelitis virus.	1. sk murine virus maintained over more than 200 serial mouse passages increased in virulence for mice from an initial intracerebral titer of about 1:1 million to a maximum titer of not less than 1:1 billion dilution activity. 2. following intracerebral injection with murine virus of remote mouse passages, 5 of 13 rhesus monkeys developed a characteristic encephalitic syndrome. repeated intravenous injection of massive doses of virus caused localized flaccid paralysis in 2 of 14 monkeys. 3. intr ...	1942	19871210
innate signaling regulates cross-priming at the level of dc licensing and not antigen presentation.	innate stimuli, such as tlr ligands, are known to greatly facilitate cross-priming. currently it is unclear whether innate stimuli enhance cross-priming at the level of cross-presentation or at the level of t-cell priming. in this study, we addressed this question by measuring cross-presentation as well as cross-priming by virus-like particles (vlp) displaying peptide p33 derived of lymphocytic choriomeningitis virus. innate stimuli were varied by either packaging different tlr ligands into viru ...	2010	19877013
on the role of the inhibitory receptor lag-3 in acute and chronic lcmv infection.	chronic viral infections are often characterized by cd8 t-cell responses with poor cytokine secretion potential and limited expansion of the cd8 t-cell pool, collectively referred to as cd8 t-cell exhaustion. exhaustion of lymphocytic choriomeningitis virus (lcmv)-specific cd8 t cells was shown to be partially regulated by the inhibitory receptor programmed death 1 (pd-1). here, we demonstrate that exhausted lcmv-specific cd8 t cells also express the negative regulatory receptor lymphocyte activ ...	2010	19880580
adenovirus e3 mhc inhibitory genes but not tnf/fas apoptotic inhibitory genes expressed in beta cells prevent autoimmune diabetes.	to mimic events and molecules involved in type 1 insulin-dependent diabetes mellitus (t1d), we previously designed a transgenic (tg) mouse model where the viral nucleoprotein (np) gene of lymphocytic choriomeningitis virus (lcmv) was expressed in the thymus to delete high affinity antiself (virus) t cells and in insulin-producing beta cells of the islets of langerhans. such tg mice, termed rip-lcmv, fail to spontaneously develop diabetes. in contrast, when these mice are challenged with lcmv, th ...	2009	19887639
[lymphocytic choriomeningitis virus and fetal anomalies.]	objective: lymphocytic choriomeningitis virus (lcmv), a rodent-borne arenavirus, is an uncommonly recognized cause of severe congenital viral infection. the incidence of this infection during pregnancy is still unknown. our study aimed to evaluate lcmv infection frequency in pregnancy with fetal neurological abnormalities of unknown etiology. material and methods: samples obtained during three years from 160 pregnant women were retrospectively analysed: 155 maternal sera, 150 amniotic fluids (af ...	2009	19896295
helicobacter spp. in wild mice (peromyscus leucopus) found in laboratory animal facilities.	wild rodents are a potential source for pathogen introduction into laboratory animal research facilities. a study was designed to assess wild mice found at our institution by infectious disease surveillance. wild white-footed mice (peromyscus leucopus) were captured with live capture traps placed in areas in which wild mice had been reported in several animal facilities. captured animals were euthanized by inhalation of co(2), blood was collected by cardiocentesis (n = 10), and necropsy was perf ...	2009	19930823
cross, but not direct, presentation of cell-associated virus antigens by spleen macrophages is influenced by their differentiation state.	the initiation of t-cell immune responses requires professional antigen-presenting cells. emerging data point towards an important role for macrophages (mphi) in the priming of naïve t cells. in this study we analyzed the efficiency and the mechanisms by which mphi derived from spleen (sp-mphi) or bone marrow (bm-mphi) present lymphocytic choriomeningitis virus (lcmv) antigens to epitope-specific t cells. we demonstrate that because of phagosomal maturation, sp-mphi downregulate their ability to ...	2010	19935765
immunization with live attenuated influenza viruses that express altered ns1 proteins results in potent and protective memory cd8+ t-cell responses.	the generation of vaccines that induce long-lived protective immunity against influenza virus infections remains a challenging goal. ideally, vaccines should elicit effective humoral and cellular immunity to protect an individual from infection or disease. cross-reactive t- and b-cell responses that are elicited by live virus infections may provide such broad protection. optimal induction of t-cell responses involves the action of type i interferons (ifn-i). influenza virus expressed nonstructur ...	2010	19939929
absence of tapasin alters immunodominance against a lymphocytic choriomeningitis virus polytope.	tapasin edits the peptide repertoire presented to cd8(+) t cells by favoring loading of slow off-rate peptides on mhc i molecules. to investigate the role of tapasin on t cell immunodominance we used poxvirus viral vectors expressing a polytope of lymphocytic choriomeningitis virus epitopes with different off-rates. in tapasin-deficient mice, responses to subdominant fast off-rate peptides were clearly favored. this alteration of the cd8(+) t cell hierarchy was a consequence of tapasin editing a ...	2010	19949070
tissue-specific differences in pd-1 and pd-l1 expression during chronic viral infection: implications for cd8 t-cell exhaustion.	the pd-1/pd-l pathway plays a major role in regulating t-cell exhaustion during chronic viral infections in animal models, as well as in humans, and blockade of this pathway can revive exhausted cd8(+) t cells. we examined the expression of pd-1 and its ligands, pd-l1 and pd-l2, in multiple tissues during the course of chronic viral infection and determined how the amount of pd-1 expressed, as well as the anatomical location, influenced the function of exhausted cd8 t cells. the amount of pd-1 o ...	2010	19955307
treatment with a sphingosine analog does not alter the outcome of a persistent virus infection.	there is no known antiviral drug treatment that routinely terminates persistent virus infections. a recent provocative report indicated that low dosage of the sphingosine analog fty720 caused lymphopenia in mice persistently infected with lymphocytic choriomeningitis virus (lcmv)-clone 13 (cl 13) and induced viral clearance within 30 days post-treatment (premenko-lanier et al., 2008). however, we find that low dosage of fty720 fails to purge lcmv-cl 13 infection and does not induce lymphopenia i ...	2010	19962171
lymphocytic choriomeningitis virus: a prenatal and postnatal threat.		2009	19968943
z proteins of new world arenaviruses bind rig-i and interfere with type i interferon induction.	the retinoic acid-inducible gene i product (rig-i) is a cellular sensor of rna virus infection that regulates the cellular beta interferon (ifn-beta) response. the nucleoproteins (np) of arenaviruses are reported to antagonize the ifn response by inhibiting interferon regulatory factor 3 (irf-3). here, we demonstrate that the z proteins of four new world (nw) arenaviruses, guanarito virus (gtov), junin virus (junv), machupo virus (mavc), and sabia virus (sabv), bind to rig-i, resulting in downre ...	2010	20007272
an interfering activity against lymphocytic choriomeningitis virus replication associated with enhanced mutagenesis.	previous studies have documented that, in the presence of the mutagenic base analogue 5-fluorouracil (fu), lymphocytic choriomeningitis virus (lcmv) that persisted in bhk-21 cells decreased its infectivity to a larger extent than intracellular viral rna levels, prior to virus extinction. this observation, together with in silico simulations, led to the proposal of the lethal defection model of virus extinction. this model suggests the participation of defective-interfering genomes in the loss of ...	2010	20007356
mice with a selective impairment of ifn-gamma signaling in macrophage lineage cells demonstrate the critical role of ifn-gamma-activated macrophages for the control of protozoan parasitic infections in vivo.	ifn-gamma has long been recognized as a cytokine with potent and varied effects in the immune response. although its effects on specific cell types have been well studied in vitro, its in vivo effects are less clearly understood because of its diverse actions on many different cell types. although control of multiple protozoan parasites is thought to depend critically on the direct action of ifn-gamma on macrophages, this premise has never been directly proven in vivo. to more directly examine t ...	2010	20018611
constitutive activation of wnt signaling favors generation of memory cd8 t cells.	t cell factor-1 (tcf-1) and lymphoid enhancer-binding factor 1, the effector transcription factors of the canonical wnt pathway, are known to be critical for normal thymocyte development. however, it is largely unknown if it has a role in regulating mature t cell activation and t cell-mediated immune responses. in this study, we demonstrate that, like il-7ralpha and cd62l, tcf-1 and lymphoid enhancer-binding factor 1 exhibit dynamic expression changes during t cell responses, being highly expres ...	2010	20026746
neutralization of ifngamma defeats haemophagocytosis in lcmv-infected perforin- and rab27a-deficient mice.	hereditary haemophagocytic lymphohistiocytosis (hlh) is a fatal inflammatory disease and treatments currently may lead to serious side effects. there is a pressing need for effective, less toxic treatments for this disease. previous reports have suggested that interferon gamma (ifngamma) has a role in the pathogenesis of hlh. here, we report that blocking ifngamma had a therapeutic effect in two different murine models of human hereditary hlh (perforin-deficient and rab27a-deficient mice, both i ...	2009	20049711
genomic and phylogenetic characterization of merino walk virus, a novel arenavirus isolated in south africa.	merino walk virus (mwv), a proposed novel tentative species of the family arenaviridae, was isolated from a rodent, myotomys unisulcatus, collected at merino walk, eastern cape, south africa, in 1985. full-length genomic sequence confirmed mwv as an arenavirus related distantly to mobala, mopeia and ippy viruses, all members of the old world arenavirus complex. we propose mwv as a tentative novel species in the lassa-lymphocytic choriomeningitis virus complex, based on its isolation from a novel ...	2010	20071489