Publications

notes from the field: a cluster of lymphocytic choriomeningitis virus infections transmitted through organ transplantation - iowa, 2013.	on april 26, 2013, the united network for organ sharing reported to cdc a cluster of ill organ transplant recipients in iowa with a common organ donor. infection with lymphocytic choriomeningitis virus (lcmv) was suspected. lcmv is a rodent-borne virus that most commonly causes nonfatal, influenza-like illness and occasional aseptic meningitis, but when transmitted through organ transplantation or in utero can cause severe, life-threatening disease.	2014	24647402
augmented replicative capacity of the boosting antigen improves the protective efficacy of heterologous prime-boost vaccine regimens.	prime-boost immunization regimens have proven efficacious at generating robust immune responses. however, whether the level of replication of the boosting antigen impacts the magnitude and protective efficacy of vaccine-elicited immune responses remains unclear. to evaluate this, we primed mice with replication-defective adenovirus vectors expressing the lymphocytic choriomeningitis virus (lcmv) glycoprotein (gp), followed by boosting with either lcmv armstrong, which is rapidly controlled, or l ...	2014	24648461
serological survey of rodent-borne viruses in finnish field voles.	in northern europe, rodent populations display cyclic density fluctuations that can be correlated with the human incidence of zoonotic diseases they spread. during density peaks, field voles (microtus agrestis) become one of the most abundant rodent species in northern europe, yet little is known of the viruses they host. we screened 709 field voles, trapped from 14 sites over 3 years, for antibodies against four rodent-borne, potentially zoonotic viruses or virus groups-hantaviruses, lymphocyti ...	2014	24689532
type i interferons directly inhibit regulatory t cells to allow optimal antiviral t cell responses during acute lcmv infection.	regulatory t (t reg) cells play an essential role in preventing autoimmunity but can also impair clearance of foreign pathogens. paradoxically, signals known to promote t reg cell function are abundant during infection and could inappropriately enhance t reg cell activity. how t reg cell function is restrained during infection to allow the generation of effective antiviral responses remains largely unclear. we demonstrate that the potent antiviral type i interferons (ifns) directly inhibit co-st ...	2014	24711580
protracted symptoms in lymphocytic choriomeningitis: a case report.	assumed to be underreported and underrecognized, lymphocytic choriomeningitis presents as a febrile illness transmitted by the common house mouse, mus musculus. although asymptomatic or mild febrile illnesses are commonplace, meningitis and meningoencephalitis may develop after symptoms have seemed to improve. neurologic sequelae are not typical but have been reported and can persist for months. we report a documented case of lymphocytic choriomeningitis in which a previously healthy 17-year-old ...	2015	24736119
irf7-dependent type i interferon production induces lethal immune-mediated disease in stat1 knockout mice infected with lymphocytic choriomeningitis virus.	following systemic infection with lymphocytic choriomeningitis virus (lcmv), stat1 knockout (ko) mice but not wild-type, stat2 ko, irf9 ko, or ifnar ko mice develop lethal disease perpetrated by cd4(+) t cells. irf7 is a key transcriptional activator of type i ifn (ifn-i) during lcmv infection. here, the role of irf7 in the lethal host response to lcmv infection in stat1 ko mice was examined. in contrast to stat1 ko mice, stat1/irf7 double ko (dko) mice survived lcmv infection with a reduced imm ...	2014	24760883
effect of weak acid hypochlorous solution on selected viruses and bacteria of laboratory rodents.	weak acid hypochlorous solution (wahs) is known to have efficacy for inactivating pathogens and to be relatively safe with respect to the live body. based on these advantages, many animal facilities have recently been introducing wahs for daily cleaning of animal houses. in this study, we determined the effect of wahs in inactivating specific pathogens of laboratory rodents and pathogens of opportunistic infection. wahs with an actual chloride concentration of 60 ppm and a ph value of 6.0 was ge ...	2014	24770639
type i interferon suppresses de novo virus-specific cd4 th1 immunity during an established persistent viral infection.	cd4 t cells are central to orchestrate, sustain, and potentially regenerate antiviral immunity throughout persistent viral infections. although the evolving immune environment during persistent infection reshapes established cd4 t-cell responses, the fate of naïve cd4 t cells primed in the midst of persistent infection is unclear. we demonstrate that, in marked contrast to the onset of infection, virus-specific cd4 t cells primed during an established persistent infection have diminished ability ...	2014	24799699
congenitally acquired persistent lymphocytic choriomeningitis viral infection reduces neuronal progenitor pools in the adult hippocampus and subventricular zone.	lymphocytic choriomeningitis virus (lcmv) can be transmitted through congenital infection, leading to persistent infection of numerous organ systems including the central nervous system (cns). adult mice persistently infected with lcmv (lcmv-cgpi mice) exhibit learning deficits, such as poor performance in spatial discrimination tests. given that deficits in spatial learning have been linked to defects in adult neurogenesis, we investigated the impact of congenital lcmv infection on generation o ...	2014	24802239
activation of endogenous type i ifn signaling contributes to persistent hcv infection.	hcv infection is a major world health problem, leading to both end-stage liver disease and primary liver cancer. great efforts have been made in developing new therapies for hcv infection; however, combination therapy with pegylated ifn-α and ribavirin (pegifn-rbv) remains the first choice of treatment for chronic hcv infection in most countries. the treatment response to pegifn-rbv remains relatively low. understanding the molecular mechanisms of persistent hcv infection and pegifn-rbv resistan ...	2014	24806972
re-engineering vesicular stomatitis virus to abrogate neurotoxicity, circumvent humoral immunity, and enhance oncolytic potency.	as cancer treatment tools, oncolytic viruses (ov) have yet to realize what some see as their ultimate clinical potential. in this study, we have engineered a chimeric vesicular stomatitis virus (vsv) that is devoid of its natural neurotoxicity while retaining potent oncolytic activity. the envelope glycoprotein (g) of vsv was replaced with a variant glycoprotein of the lymphocytic choriomeningitis virus (lcmv-gp), creating a replicating therapeutic, rvsv(gp), that is benign in normal brain but c ...	2014	24812275
evolution of recombinant lymphocytic choriomeningitis virus/lassa virus in vivo highlights the importance of the gpc cytosolic tail in viral fitness.	a key characteristic of arenaviruses is their ability to establish persistent infection in their natural host. different factors like host age, viral dose strain, and route of infection may contribute to the establishment of persistence. however, the molecular mechanisms governing persistence are not fully understood. here, we describe gain-of-function mutations of lymphocytic choriomeningitis virus (lcmv) expressing lassa virus (lasv) gp, which can prolong viremia in mice depending on the seque ...	2014	24829355
notes from the field: a cluster of lymphocytic choriomeningitis virus infections transmitted through organ transplantation-iowa, 2013.		2014	24854024
dynamic functional modulation of cd4+ t cell recall responses is dependent on the inflammatory environment of the secondary stimulus.	the parameters that modulate the functional capacity of secondary th1 effector cells are poorly understood. in this study, we employ a serial adoptive transfer model system to show that the functional differentiation and secondary memory potential of secondary cd4+ effector t cells are dependent on the inflammatory environment of the secondary challenge. adoptive transfer of tcr transgenic lymphocytic choriomeningitis virus (lcmv) glycoprotein-specific smarta memory cells into lcmv-immune hosts, ...	2014	24854337
epigenetic manipulation restores functions of defective cd8⁺ t cells from chronic viral infection.	functional exhaustion of antigen-specific t cells is a defining characteristic of many chronic infections, but the underlying mechanisms of t cell dysfunction are not well understood. epigenetics plays an important role in the control of t cell development, differentiation, and function. to examine if epigenetics also plays a role in t cell exhaustion, we analyzed chromatin remodeling in cd8(+) t cells from mice with chronic lymphocytic choriomeningitis virus infection. we observed downregulatio ...	2014	24861055
type i interferon is a therapeutic target for virus-induced lethal vascular damage.	the outcome of a viral infection reflects the balance between virus virulence and host susceptibility. the clone 13 (cl13) variant of lymphocytic choriomeningitis virus--a prototype of old world arenaviruses closely related to lassa fever virus--elicits in c57bl/6 and balb/c mice abundant negative immunoregulatory molecules, associated with t-cell exhaustion, negligible t-cell-mediated injury, and high virus titers that persist. conversely, here we report that in nzb mice, despite the efficient ...	2014	24889626
the pulmonary localization of virus-specific t lymphocytes is governed by the tissue tropism of infection.	the migration of pathogen-specific t cells into nonlymphoid tissues, such as the lung, is critical to control peripheral infections. use of in vivo intravascular labeling of leukocytes has allowed for improved discrimination between cells located in the blood from cells present within peripheral tissues, such as the lung. this is particularly important in the lung, which is comprised of an intricate network of blood vessels that harbors a large proportion of the total blood volume at any given t ...	2014	24899187
type i interferon protects antiviral cd8+ t cells from nk cell cytotoxicity.	despite development of new antiviral drugs, viral infections are still a major health problem. the most potent antiviral defense mechanism is the innate production of type i interferon (ifn-i), which not only limits virus replication but also promotes antiviral t cell immunity through mechanisms, which remain insufficiently studied. using the murine lymphocytic choriomeningitis virus model system, we show here that ifn-i signaling on t cells prevented their rapid elimination in vivo. microarray ...	2014	24909887
type i interferons protect t cells against nk cell attack mediated by the activating receptor ncr1.	direct type i interferon (ifn) signaling on t cells is necessary for the proper expansion, differentiation, and survival of responding t cells following infection with viruses prominently inducing type i ifn. the reasons for the abortive response of t cells lacking the type i ifn receptor (ifnar1(-/-)) remain unclear. we report here that ifnar1(-/-) t cells were highly susceptible to natural killer (nk) cell-mediated killing in a perforin-dependent manner. depletion of nk cells prior to lymphocy ...	2014	24909889
costimulatory tnfr family members in control of viral infection: outstanding questions.	members of the tnfr family can play prominent roles in controlling the magnitude, duration and phenotype of the immune response to viruses. the importance of particular tnfrs in different viral infections and whether they contribute to viral control or pathology is dependent on the virus and the severity of the infection. tnfrs and their ligands are widely and differentially expressed on both adaptive and innate immune cell types. the cell types through which tnfrs exert their effects, the uniqu ...	2014	24910294
loss of the death receptor cd95 (fas) expression by dendritic cells protects from a chronic viral infection.	chronic viral infections incapacitate adaptive immune responses by "exhausting" virus-specific t cells, inducing their deletion and reducing productive t-cell memory. viral infection rapidly induces death receptor cd95 (fas) expression by dendritic cells (dcs), making them susceptible to elimination by the immune response. lymphocytic choriomeningitis virus (lcmv) clone 13, which normally establishes a chronic infection, is rapidly cleared in c57black6/j mice with conditional deletion of fas in ...	2014	24912151
solid organ transplant donors with central nervous system infection.	while donor-derived infections (ddi) remain uncommon, multiple reports describe ddi with pathogens that cause central nervous system (cns) infection resulting in significant recipient disease. the ad hoc disease transmission advisory committee (dtac) reviewed the records of potential donor-derived disease transmission events (pddte) to describe donor characteristics and outcomes associated with ddi from cns pathogens.	2014	24914569
structure of the lcmv nucleoprotein provides a template for understanding arenavirus replication and immunosuppression.	the x-ray crystal structure of the lymphocytic choriomeningitis virus nucleoprotein c-terminal immunosuppressive domain (lcmv npδ340) was determined to 2.0 å resolution. the structure indicates that lcmv npδ340, like the other structurally characterized arenaviral nucleoproteins, adopts the fold of an exonuclease. this structure provides a crucial three-dimensional template for functional exploration of the replication and immunosuppression of this prototypic arenavirus.	2014	24914986
multiple infections of rodents with zoonotic pathogens in austria.	rodents are important reservoirs for a large number of zoonotic pathogens. we examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, leptospira spp., borrelia spp., rickettsia spp., bartonella spp., coxiella burnetii, and toxoplasma gondii. in 2008, 110 rodents of four species (40 clethrionomys glareolus, 29 apodemus flavicollis, 26 apodemus sylvaticus, and ...	2014	24915446
cell entry of lymphocytic choriomeningitis virus is restricted in myotubes.	in mice persistently infected since birth with the prototypic arenavirus lymphocytic choriomeningitis viurs, viral antigen and rna are readily detected in most organs and cell types but remarkably absent in skeletal muscle. here we report that mouse c2c12 myoblasts that are readily infected by lcmv, become highly refractory to lcmv infection upon their differentiation into myotubes. myotube's resistance to lcmv was not due to an intracellular restriction of virus replication but rather an impair ...	2014	24928036
acute and chronic b cell depletion disrupts cd4+ and cd8+ t cell homeostasis and expansion during acute viral infection in mice.	b cells provide humoral protection against pathogens and promote cellular immunity through diverse nonclassical effector functions. to assess b cell function in promoting t cell homeostasis, mature b cells were either acutely or chronically depleted in mice using cd20 mab. acute b cell depletion in either 2- or 4-mo-old mice significantly reduced spleen and lymph node cd4(+) and cd8(+) t cell numbers, including naive, activated, and foxp3(+)cd25(+)cd4(+) regulatory t cell subsets. the numbers of ...	2014	24928986
regulation of tissue-dependent differences in cd8+ t cell apoptosis during viral infection.	virus-specific cd8+ t cells in the lymphoid organs contract at the resolution of virus infections by apoptosis or by dissemination into peripheral tissues, and those residing in nonlymphoid organs, including the peritoneal cavity and fat pads, are more resistant to apoptosis than those in the spleen and lymph nodes. this stability of memory t cells in the nonlymphoid tissues may enhance protection to secondary challenges. here, we show that lymphocytic choriomeningitis virus (lcmv)-specific cd8+ ...	2014	24942579
spleen-derived macrophages are readily polarized into classically activated (m1) or alternatively activated (m2) states.	bone marrow derived macrophages (bm-mφ) that differentiate from precursor cells can be polarized into classically activated pro-inflammatory (m1) or alternatively activated (m2) states depending upon the cytokine microenvironment. we questioned whether tissue mφ, such as spleen-derived mφ (sp-mφ), have the ability to differentiate into m1 or m2 cells. we show in response to activation with ifn-gamma (ifn-γ) and lipopolysaccharide (lps), that the sp-mφ readily acquired an m1 status indicated by u ...	2014	24954891
conventional but not plasmacytoid dendritic cells foster the systemic virus-induced type i ifn response needed for efficient cd8 t cell priming.	plasmacytoid dendritic cells (pdcs) are considered to be the principal type-i ifn (ifn-i) source in response to viruses, whereas the contribution of conventional dcs (cdcs) has been underestimated because, on a per-cell basis, they are not considered professional ifn-i-producing cells. we have investigated their respective roles in the ifn-i response required for ctl activation. using a nonreplicative virus, baculovirus, we show that despite the high ifn-i-producing abilities of pdcs, in vivo cd ...	2014	24973449
the regulatory t cell effector molecule fibrinogen-like protein 2 is necessary for the development of rapamycin-induced tolerance to fully mhc-mismatched murine cardiac allografts.	therapies that promote tolerance in solid organ transplantation will improve patient outcomes by eliminating the need for long-term immunosuppression. to investigate mechanisms of rapamycin-induced tolerance, c3h/hej mice were heterotopically transplanted with mhc-mismatched hearts from balb/cj mice and were monitored for rejection after a short course of rapamycin treatment. mice that had received rapamycin developed tolerance with indefinite graft survival, whereas untreated mice all rejected ...	2015	24990517
chronic viral infection promotes sustained th1-derived immunoregulatory il-10 via blimp-1.	during the course of many chronic viral infections, the antiviral t cell response becomes attenuated through a process that is regulated in part by the host. while elevated expression of the immunosuppressive cytokine il-10 is involved in the suppression of viral-specific t cell responses, the relevant cellular sources of il-10, as well as the pathways responsible for il-10 induction, remain unclear. in this study, we traced il-10 production over the course of chronic lymphocytic choriomeningiti ...	2014	25003188
diseases of the central nervous system caused by lymphocytic choriomeningitis virus and other arenaviruses.		2014	25015511
[meningitis after a mouse bite].	infection with the lymphocytic choriomeningitis virus is a human zoonosis caused by a rodent-borne arenavirus and is often seen in autumn and winter when mice retreat into houses. infection in humans is acquired after inhalation of aerosols or direct contact with excreta of an infected rodent.	2014	25017980
viral causes of hearing loss: a review for hearing health professionals.	a number of viral infections can cause hearing loss. hearing loss induced by these viruses can be congenital or acquired, unilateral or bilateral. certain viral infections can directly damage inner ear structures, others can induce inflammatory responses which then cause this damage, and still others can increase susceptibility or bacterial or fungal infection, leading to hearing loss. typically, virus-induced hearing loss is sensorineural, although conductive and mixed hearing losses can be see ...	2014	25080364
mhc basis of t cell-dependent heterologous immunity to arenaviruses.	having a history of infection with one pathogen may sometimes provide a level of t cell-dependent protective heterologous immunity to another pathogen. this immunity was initially thought due to cross-reactive t cell epitopes, but recent work has suggested that such protective immunity can be initiated nonspecifically by the action of cytokines on memory t cells. we retested this concept using two small and well-defined arenaviruses, lymphocytic choriomeningitis virus (lcmv) and pichinde virus ( ...	2014	25094042
interplay between regulatory t cells and pd-1 in modulating t cell exhaustion and viral control during chronic lcmv infection.	regulatory t (t reg) cells are critical for preventing autoimmunity mediated by self-reactive t cells, but their role in modulating immune responses during chronic viral infection is not well defined. to address this question and to investigate a role for t reg cells in exhaustion of virus-specific cd8 t cells, we depleted t reg cells in mice chronically infected with lymphocytic choriomeningitis virus (lcmv). t reg cell ablation resulted in 10-100-fold expansion of functional lcmv-specific cd8 ...	2014	25113973
differences in the transduction of canonical wnt signals demarcate effector and memory cd8 t cells with distinct recall proliferation capacity.	protection against reinfection is mediated by ag-specific memory cd8 t cells, which display stem cell-like function. because canonical wnt (wingless/int1) signals critically regulate renewal versus differentiation of adult stem cells, we evaluated wnt signal transduction in cd8 t cells during an immune response to acute infection with lymphocytic choriomeningitis virus. whereas naive cd8 t cells efficiently transduced wnt signals, at the peak of the primary response to infection only a fraction ...	2014	25127860
gammaherpesvirus latency differentially impacts the generation of primary versus secondary memory cd8+ t cells during subsequent infection.	unlike laboratory animals, humans are infected with multiple pathogens, including the highly prevalent herpesviruses. the purpose of these studies was to determine the effect of gammaherpesvirus latency on t cell number and differentiation during subsequent heterologous viral infections. mice were first infected with murine gammaherpesvirus 68 (mhv68), a model of epstein-barr virus (ebv) infection, and then after latency was established, they were challenged with the armstrong strain of lymphocy ...	2014	25142586
in vivo rna interference screens identify regulators of antiviral cd4(+) and cd8(+) t cell differentiation.	classical genetic approaches to examine the requirements of genes for t cell differentiation during infection are time consuming. here we developed a pooled approach to screen 30-100+ genes individually in separate antigen-specific t cells during infection using short hairpin rnas in a microrna context (shrnamir). independent screens using t cell receptor (tcr)-transgenic cd4(+) and cd8(+) t cells responding to lymphocytic choriomeningitis virus (lcmv) identified multiple genes that regulated de ...	2014	25148027
encephalitis caused by pathogens transmitted through organ transplants, united states, 2002-2013.	the cause of encephalitis among solid organ transplant recipients may be multifactorial; the disease can result from infectious or noninfectious etiologies. during 2002-2013, the us centers for disease control and prevention investigated several encephalitis clusters among transplant recipients. cases were caused by infections from transplant-transmitted pathogens: west nile virus, rabies virus, lymphocytic choriomeningitis virus, and balamuthia mandrillaris amebae. in many of the clusters, iden ...	0	25148201
enhancing t cell immune responses by b cell-based therapeutic vaccine against chronic virus infection.	chronic virus infection leads to the functional impairment of dendritic cells (dcs) as well as t cells, limiting the clinical usefulness of dc-based therapeutic vaccine against chronic virus infection. meanwhile, b cells have been known to maintain the ability to differentiate plasma cells producing antibodies even during chronic virus infection. previously, α-galactosylceramide (αgc) and cognate peptide-loaded b cells were comparable to dcs in priming peptide-specific cd8(+) t cells as antigen ...	2014	25177253
the role of myeloid cell activation and arginine metabolism in the pathogenesis of virus-induced diseases.	when an antiviral immune response is generated, a balance must be reached between two opposing pathways: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activitie ...	2014	25250029
suppressors of cytokine signaling 1 and 3 are upregulated in brain resident cells in response to virus-induced inflammation of the central nervous system via at least two distinctive pathways.	suppressors of cytokine signaling (socs) proteins are intracellular proteins that inhibit cytokine signaling in a variety of cell types. a number of viral infections have been associated with socs upregulation; however, not much is known about the mechanisms regulating socs expression during viral infection. in this study, we used two pathologically distinct intracerebral (i.c.) infection models to characterize temporal and spatial aspects of socs expression in the virus-infected central nervous ...	2014	25253351
toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection.	during virus infection and autoimmune disease, inflammatory dendritic cells (idcs) differentiate from blood monocytes and infiltrate infected tissue. following acute infection with hepatotropic viruses, idcs are essential for re-stimulating virus-specific cd8(+) t cells and therefore contribute to virus control. here we used the lymphocytic choriomeningitis virus (lcmv) model system to identify novel signals, which influence the recruitment and activation of idcs in the liver. we observed that i ...	2015	25257173
anti-gitr agonist therapy intrinsically enhances cd8 t cell responses to chronic lymphocytic choriomeningitis virus (lcmv), thereby circumventing lcmv-induced downregulation of costimulatory gitr ligand on apc.	the costimulatory tnfr family member gitr can provide important survival signals for cd8 t cells. however, little is known about the regulation of this pathway during a chronic infection. in this study, we show that gitr ligand (gitrl) is maximally induced on apcs at day 2 post-lymphocytic choriomeningitis virus (lcmv) clone 13 infection, but is downregulated to below baseline levels by day 8 postinfection (p.i.), and remains so at the chronic stage of infection. at its peak, gitrl expression is ...	2014	25281716
vitamin d receptor signals regulate effector and memory cd8 t cell responses to infections in mice.	vitamin d insufficiency is associated with broad-ranging human disease sequelae such as bone disease, cancer, cardiovascular disease, allergy, autoimmune disorders, diabetes, and infectious diseases. disease risk and severity of a large proportion of the nonskeletal disorders heavily involve the cytotoxic cluster of differentiation (cd) 8 t lymphocyte (ctl) arm of cellular adaptive immunity. considering the importance of vitamin d in ctl-dependent diseases, there is a critical need for systemati ...	2014	25320188
hdac1 controls cd8+ t cell homeostasis and antiviral response.	reversible lysine acetylation plays an important role in the regulation of t cell responses. hdac1 has been shown to control peripheral t helper cells, however the role of hdac1 in cd8+ t cell function remains elusive. by using conditional gene targeting approaches, we show that lckcre-mediated deletion of hdac1 led to reduced numbers of thymocytes as well as peripheral t cells, and to an increased fraction of cd8+cd4- cells within the cd3/tcrβlo population, indicating that hdac1 is essential fo ...	2014	25333902
cd8 t cells in innate immune responses: using stat4-dependent but antigen-independent pathways to gamma interferon during viral infection.	the cytokine gamma interferon (ifn-γ), with antimicrobial and immunoregulatory functions, can be produced by t cells following stimulation through their t cell receptors (tcrs) for antigen. the innate cytokines type 1 ifns and interleukin-12 (il-12) can also stimulate ifn-γ production by natural killer (nk) but not naive t cells. high basal expression of signal transducer and activator of transcription 4 (stat4), used by type 1 ifn and il-12 to induce ifn-γ as well as cd25, contributes to the nk ...	2014	25336459
arenavirus stable signal peptide is the keystone subunit for glycoprotein complex organization.	the rodent arenavirus glycoprotein complex encodes a stable signal peptide (ssp) that is an essential structural component of mature virions. the ssp, gp1, and gp2 subunits of the trimeric glycoprotein complex noncovalently interact to stud the surface of virions and initiate arenavirus infectivity. nascent glycoprotein production undergoes two proteolytic cleavage events: first within the endoplasmic reticulum (er) to cleave ssp from the remaining precursor gp1/2 (glycoprotein complex [gpc]) gl ...	2014	25352624
autophagy is essential for effector cd8(+) t cell survival and memory formation.	the importance of autophagy in the generation of memory cd8(+) t cells in vivo is not well defined. we report here that autophagy was dynamically regulated in virus-specific cd8(+) t cells during acute infection of mice with lymphocytic choriomeningitis virus. in contrast to the current paradigm, autophagy decreased in activated proliferating effector cd8(+) t cells and was then upregulated when the cells stopped dividing just before the contraction phase. consistent with those findings, deletio ...	2014	25362489
evidence of lymphocytic choriomeningitis virus (lcmv) in domestic mice in gabon: risk of emergence of lcmv encephalitis in central africa.	lymphocytic choriomeningitis virus (lcmv) can cause acute fatal disease on all continents but was never detected in africa. we report the first detection of lcmv rna in a common european house mouse (mus musculus domesticus) in africa. phylogenetic analyses show a close relationship with north american strains. these findings suggest that there is a risk of the appearance of lcmv acute encephalitis cases. this is a perfect example of virus dissemination by its natural host that may have dramatic ...	2015	25378495
diet-induced obesity does not impact the generation and maintenance of primary memory cd8 t cells.	the extent to which obesity compromises the differentiation and maintenance of protective memory cd8 t cell responses and renders obese individuals susceptible to infection remains unknown. in this study, we show that diet-induced obesity did not impact the maintenance of pre-existing memory cd8 t cells, including acquisition of a long-term memory phenotype (i.e., cd27(hi), cd62l(hi), klrg1(lo)) and function (i.e., cytokine production, secondary expansion, and memory cd8 t cell-mediated protecti ...	2014	25378592
t-cell stat3 is required for the maintenance of humoral immunity to lcmv.	stat3 is a critical transcription factor activated downstream of cytokine signaling and is integral for the function of multiple immune cell types. human mutations in stat3 cause primary immunodeficiency resulting in impaired control of a variety of infections, including reactivation of latent viruses. in this study, we investigate how t-cell functions of stat3 contribute to responses to viral infection by inducing chronic lymphocytic choriomeningitis virus (lcmv) infection in mice lacking stat3 ...	2015	25393615
lymphocytic choriomeningitis virus persistence promotes effector-like memory differentiation and enhances mucosal t cell distribution.	vaccines are desired that maintain abundant memory t cells at nonlymphoid sites of microbial exposure, where they may be anatomically positioned for immediate pathogen interception. here, we test the impact of antigen persistence on mouse cd8 and cd4 t cell distribution and differentiation by comparing responses to infections with different strains of lcmv that cause either acute or chronic infections. we used in vivo labeling techniques that discriminate between t cells present within tissues a ...	2015	25395301
pseudotyping lentiviral vectors with lymphocytic choriomeningitis virus glycoproteins for transduction of dendritic cells and in vivo immunization.	lentiviral vectors (lvs) are promising delivery systems for gene therapy, and they can be further engineered to increase their potential for effectively delivering transgenes to desired cell populations. here, we have engineered lvs pseudotyped with envelope glycoproteins derived from lymphocytic choriomeningitis virus (lcmv) for antigen delivery to elicit vaccine-directed immune responses. two variants, lcmv-we and lcmv-arm53b, were evaluated for their ability to mediate lv-based cellular trans ...	2014	25416034
the transcription factor foxo1 sustains expression of the inhibitory receptor pd-1 and survival of antiviral cd8(+) t cells during chronic infection.	protein kinase b (also known as akt) and the mechanistic target of rapamycin (mtor) are central regulators of t cell differentiation, proliferation, metabolism, and survival. here, we show that during chronic murine lymphocytic choriomeningitis virus infection, activation of akt and mtor are impaired in antiviral cytotoxic t lymphocytes (ctls), resulting in enhanced activity of the transcription factor foxo1. blockade of inhibitory receptor programmed cell death protein 1 (pd-1) in vivo increase ...	2014	25464856
regulatory t cells resist virus infection-induced apoptosis.	regulatory t (treg) cells are important in the maintenance of self-tolerance, and the depletion of treg cells correlates with autoimmune development. it has been shown that type i interferon (ifn) responses induced early in the infection of mice can drive memory (cd44hi) cd8 and cd4 t cells into apoptosis, and we questioned here whether the apoptosis of cd44-expressing treg cells might be involved in the infection-associated autoimmune development. instead, we found that treg cells were much mor ...	2015	25473049
fas regulates neutrophil lifespan during viral and bacterial infection.	the regulation of neutrophil lifespan is critical for a circumscribed immune response. neutrophils are sensitive to fas/cd95 death receptor signaling in vitro, but it is unknown if fas regulates neutrophil lifespan in vivo. we hypothesized that fasl-expressing cd8(+) t cells, which kill antigen-stimulated t cells during chronic viral infection, can also induce neutrophil death in tissues during infection. with the use of lysm-cre fas(fl/fl) mice, which lack fas expression in macrophages and neut ...	2015	25473101
cd8+ t cells control ross river virus infection in musculoskeletal tissues of infected mice.	ross river virus (rrv), chikungunya virus, and related alphaviruses cause debilitating polyarthralgia and myalgia. mouse models of rrv and chikungunya virus have demonstrated a role for the adaptive immune response in the control of these infections. however, questions remain regarding the role for t cells in viral control, including the magnitude, location, and dynamics of cd8(+) t cell responses. to address these questions, we generated a recombinant rrv expressing the h-2(b)-restricted glycop ...	2014	25488988
plasmodium suppresses expansion of t cell responses to heterologous infections.	plasmodium remains a major pathogen causing malaria and impairing defense against other infections. defining how plasmodium increases susceptibility to heterologous pathogens may lead to interventions that mitigate the severity of coinfections. previous studies proposed that reduced t cell responses during coinfections are due to diminished recruitment of naive t cells through infection-induced decreases in chemokine ccl21. we found that, although listeria infections reduced expression of ccl21 ...	2015	25505280
ptpn22 controls virally-induced autoimmune diabetes by modulating cytotoxic t lymphocyte responses in an epitope-specific manner.	ptpn22 is one of the most potent autoimmunity predisposing genes and strongly associates with type 1 diabetes (t1d). previous studies showed that non-obese diabetic mice with reduced expression levels of ptpn22 are protected from t1d due to increased number of t regulatory (treg) cells. we report that lack of ptpn22 exacerbates virally-induced t1d in female rat insulin promoter lymphocytic choriomeningitis virus (rip-lcmv-gp) mice, while maintaining higher number of treg cells throughout the ant ...	2015	25513733
a novel immunoregulatory role for nk-cell cytotoxicity in protection from hlh-like immunopathology in mice.	the impairment of cytotoxic activity of lymphocytes disturbs immune surveillance and leads to the development of hemophagocytic lymphohistiocytic syndrome (hlh). although cytotoxic t lymphocyte (ctl) control of hlh development is well documented, the role for natural killer (nk)-cell effector functions in the pathogenesis of this immune disorder remains unclear. in this study, we specifically targeted a defect in cytotoxicity to either ctl or nk cells in mice so as to dissect the contribution of ...	2015	25525117
the z proteins of pathogenic but not nonpathogenic arenaviruses inhibit rig-i-like receptor-dependent interferon production.	arenavirus pathogens cause a wide spectrum of diseases in humans ranging from central nervous system disease to lethal hemorrhagic fevers with few treatment options. the reason why some arenaviruses can cause severe human diseases while others cannot is unknown. we find that the z proteins of all known pathogenic arenaviruses, lymphocytic choriomeningitis virus (lcmv) and lassa, junin, machupo, sabia, guanarito, chapare, dandenong, and lujo viruses, can inhibit retinoic acid-inducible gene 1 (ri ...	2015	25552708
ebola virus and severe acute respiratory syndrome coronavirus display late cell entry kinetics: evidence that transport to npc1+ endolysosomes is a rate-defining step.	ebola virus (ebov) causes hemorrhagic fevers with high mortality rates. during cellular entry, the virus is internalized by macropinocytosis and trafficked through endosomes until fusion between the viral and an endosomal membrane is triggered, releasing the rna genome into the cytoplasm. we found that while macropinocytotic uptake of filamentous ebov viruslike particles (vlps) expressing the ebov glycoprotein (gp) occurs relatively quickly, vlps only begin to enter the cytoplasm after a 30-min ...	2015	25552710
protective efficacy of individual cd8+ t cell specificities in chronic viral infection.	specific cd8(+) t cells (ctls) play an important role in resolving protracted infection with hepatitis b and c virus in humans and lymphocytic choriomeningitis virus (lcmv) in mice. the contribution of individual ctl specificities to chronic virus control, as well as epitope-specific patterns in timing and persistence of antiviral selection pressure, remain, however, incompletely defined. to monitor and characterize the antiviral efficacy of individual ctl specificities throughout the course of ...	2015	25567678
early virus-host interactions dictate the course of a persistent infection.	many persistent viral infections are characterized by a hypofunctional t cell response and the upregulation of negative immune regulators. these events occur days after the initiation of infection. however, the very early host-virus interactions that determine the establishment of viral persistence remain poorly uncharacterized. here we show that to establish persistence, lcmv must counteract an innate anti-viral immune response within eight hours after infection. while the virus triggers cytopl ...	2015	25569216
maternal onset de novo sh2d1a mutation and lymphocytic choriomeningitis virus infection in a patient with x‑linked lymphoproliferative disease type 1: a case report.	x‑linked lymphoproliferative disease type 1 (xlp1) is a rare genetic immunodeficiency disease, which occurs due to germline mutations in the sh2d1a gene. this gene has been reported to encode the adaptor molecule signaling lymphocytic activation molecule‑associated protein xlp1 is generally triggered by the epstein‑barr virus (ebv) infection. the present study reported the case of a 4‑year‑old male who presented with a high fever, hypogammaglobulinemia, diffuse lung disease and encephalitis. the ...	2015	25572984
constitutive but not inducible attenuation of transforming growth factor β signaling increases natural killer cell responses without directly affecting dendritic cells early after persistent viral infection.	rapid innate responses to viral encounters are crucial to shaping the outcome of infection, from viral clearance to persistence. transforming growth factor β (tgf-β) is a potent immune suppressor that is upregulated early upon viral infection and maintained during chronic infections in both mice and humans. however, the role of tgf-β signaling in regulating individual cell types in vivo is still unclear. using infections with two different persistent viruses, murine cytomegalovirus (mcmv) and ly ...	2015	25589641
development of live-attenuated arenavirus vaccines based on codon deoptimization.	arenaviruses have a significant impact on public health and pose a credible biodefense threat, but the development of safe and effective arenavirus vaccines has remained elusive, and currently, no food and drug administration (fda)-licensed arenavirus vaccines are available. here, we explored the use of a codon deoptimization (cd)-based approach as a novel strategy to develop live-attenuated arenavirus vaccines. we recoded the nucleoprotein (np) of the prototypic arenavirus lymphocytic choriomen ...	2015	25589652
gitr intrinsically sustains early type 1 and late follicular helper cd4 t cell accumulation to control a chronic viral infection.	cd4 t cells are critical for control of persistent infections; however, the key signals that regulate cd4 t help during chronic infection remain incompletely defined. while several studies have addressed the role of inhibitory receptors and soluble factors such as pd-1 and il-10, significantly less work has addressed the role of t cell co-stimulatory molecules during chronic viral infection. here we show that during a persistent infection with lymphocytic choriomeningitis virus (lcmv) clone 13, ...	2015	25590581
vaccine-elicited cd4 t cells induce immunopathology after chronic lcmv infection.	cd4 t cells promote innate and adaptive immune responses, but how vaccine-elicited cd4 t cells contribute to immune protection remains unclear. we evaluated whether induction of virus-specific cd4 t cells by vaccination would protect mice against infection with chronic lymphocytic choriomeningitis virus (lcmv). immunization with vaccines that selectively induced cd4 t cell responses resulted in catastrophic inflammation and mortality after challenge with a persistent strain of lcmv. immunopathol ...	2015	25593185
type i interferons in infectious disease.	type i interferons (ifns) have diverse effects on innate and adaptive immune cells during infection with viruses, bacteria, parasites and fungi, directly and/or indirectly through the induction of other mediators. type i ifns are important for host defence against viruses. however, recently, they have been shown to cause immunopathology in some acute viral infections, such as influenza virus infection. conversely, they can lead to immunosuppression during chronic viral infections, such as lympho ...	2015	25614319
rodents and risk in the mekong delta of vietnam: seroprevalence of selected zoonotic viruses in rodents and humans.	in the mekong delta in southern vietnam, rats are commonly traded in wet markets and sold live for food consumption. we investigated seroprevalence to selected groups of rodent-borne viruses among human populations with high levels of animal exposure and among co-located rodent populations. the indirect fluorescence antibody test (ifat) was used to determine seropositivity to representative reference strains of hantaviruses (dobrava virus [dobv], seoul virus [seov]), cowpox virus, arenaviruses ( ...	0	25629782
ctla-4 blockade plus adoptive t-cell transfer promotes optimal melanoma immunity in mice.	immunotherapeutic approaches to the treatment of advanced melanoma have relied on strategies that augment the responsiveness of endogenous tumor-specific t-cell populations [eg, cytotoxic t lymphocyte-associated antigen 4 (ctla-4) blockade-mediated checkpoint inhibition] or introduce exogenously prepared tumor-specific t-cell populations [eg, adoptive cell transfer (act)]. although both approaches have shown considerable promise, response rates to these therapies remain suboptimal. we hypothesiz ...	2016	25658614
t cell expansion is the limiting factor of virus control in mice with attenuated tcr signaling: implications for human immunodeficiency.	defining the minimal thresholds for effective antiviral t cell immunity is important for clinical decisions in immunodeficient patients. tcr signaling is critical for t cell development, activation, and effector functions. in this article, we analyzed which of these tcr-mediated processes is limiting for antiviral immunity in a mouse strain with reduced expression of slp-76 (twp mice). despite severe t cell activation defects in vitro, twp mice generated a normal proportion of antiviral effector ...	2015	25672755
inflammatory monocytes recruited to the liver within 24 hours after virus-induced inflammation resemble kupffer cells but are functionally distinct.	due to a scarcity of immunocompetent animal models for viral hepatitis, little is known about the early innate immune responses in the liver. in various hepatotoxic models, both pro- and anti-inflammatory activities of recruited monocytes have been described. in this study, we compared the effect of liver inflammation induced by the toll-like receptor 4 ligand lipopolysaccharide (lps) with that of a persistent virus, lymphocytic choriomeningitis virus (lcmv) clone 13, on early innate intrahepati ...	2015	25673700
deficiency of the b cell-activating factor receptor results in limited cd169+ macrophage function during viral infection.	the b cell-activating factor (baff) is critical for b cell development and humoral immunity in mice and humans. while the role of baff in b cells has been widely described, its role in innate immunity remains unknown. using baff receptor (baffr)-deficient mice, we characterized baffr-related innate and adaptive immune functions following infection with vesicular stomatitis virus (vsv) and lymphocytic choriomeningitis virus (lcmv). we identified a critical role for baffr signaling in the generati ...	2015	25673724
targeting of non-dominant antigens as a vaccine strategy to broaden t-cell responses during chronic viral infection.	in this study, we compared adenoviral vaccine vectors with the capacity to induce equally potent immune responses against non-dominant and immunodominant epitopes of murine lymphocytic choriomeningitis virus (lcmv). our results demonstrate that vaccination targeting non-dominant epitopes facilitates potent virus-induced t-cell responses against immunodominant epitopes during subsequent challenge with highly invasive virus. in contrast, when an immunodominant epitope was included in the vaccine, ...	2015	25679375
antibody effector functions mediated by fcγ-receptors are compromised during persistent viral infection.	t cell dysfunction is well documented during chronic viral infections but little is known about functional abnormalities in humoral immunity. here we report that mice persistently infected with lymphocytic choriomeningitis virus (lcmv) exhibit a severe defect in fcγ-receptor (fcγr)-mediated antibody effector functions. using transgenic mice expressing human cd20, we found that chronic lcmv infection impaired the depletion of b cells with rituximab, an anti-cd20 antibody widely used for the treat ...	2015	25680276
suppression of fcγ-receptor-mediated antibody effector function during persistent viral infection.	understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. t cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (lcmv) suppressed multiple fcγ-receptor (fcγr) functions. the high amounts of immune complexes suppressed ...	2015	25680277
enhanced cd8 t cell responses through gitr-mediated costimulation resolve chronic viral infection.	chronic infections are characterized by the inability to eliminate the persisting pathogen and often associated with functional impairment of virus-specific t-cell responses. costimulation through glucocorticoid-induced tnfr-related protein (gitr) can increase survival and function of effector t cells. here, we report that constitutive expression of gitr-ligand (gitrl) confers protection against chronic lymphocytic choriomeningitis virus (lcmv) infection, accelerating recovery without increasing ...	2015	25738498
functional restoration of exhausted cd4(+) and cd8(+) t cells in chronic viral infection by vinegar-processed flos of daphne genkwa.	t-cell exhaustion has become an important issue in chronic infection because exhausted antigen-specific t cells show impaired abilities to eradicate persistently infected pathogens and produce effector cytokines, such as ifn-γ and tnf-α. thus, strategies to either restore endogenous exhausted t cell responses or provide functional t cells are needed for therapeutics of chronic infection. despite promising developments using antibodies and cell immunotherapy, there have been no reported attempts ...	2015	25744061
t-cell exhaustion in chronic hepatitis b infection: current knowledge and clinical significance.	hepatitis b virus (hbv) infection is the major cause of inflammatory liver disease, of which the clinical recovery and effective anti-viral therapy is associated with the sustained viral control of effector t cells. in humans, chronic hbv infection often shows weak or absent virus-specific t-cell reactivity, which is described as the 'exhaustion' state characterized by poor effector cytotoxic activity, impaired cytokine production and sustained expression of multiple inhibitory receptors, such a ...	2015	25789969
prostaglandin e2 and programmed cell death 1 signaling coordinately impair ctl function and survival during chronic viral infection.	more than 10% of the world's population is chronically infected with hiv, hepatitis c virus (hcv) or hepatitis b virus (hbv), all of which can cause severe disease and death. these viruses persist in part because continuous antigenic stimulation causes the deterioration of virus-specific cytotoxic t lymphocyte (ctl) function and survival. additionally, antiviral ctls autonomously suppress their responses to limit immunopathology by upregulating inhibitory receptors such as programmed cell death ...	2015	25799228
analgesia in mice with experimental meningitis reduces pain without altering immune parameters.	intracranial lymphocytic choriomeningitis virus (lcmv) infection is a widely used animal model to study virus-induced cytotoxic t cell (ctl) mediated meningitis and immunopathology. nevertheless, this model causes severe pain and distress in mice, especially at later stages of the disease. therefore, new treatment regimens to improve animal welfare have to be developed. in this study, we subcutaneously implanted alzet® osmotic pumps continuously releasing buprenorphine to reduce pain in mice wit ...	2015	25800953
modulation of siv and hiv dna vaccine immunity by fas-fasl signaling.	signaling through the fas/apo-1/cd95 death receptor is known to affect virus-specific cell-mediated immune (cmi) responses. we tested whether modulating the fas-apoptotic pathway can enhance immune responses to dna vaccination or lymphocytic choriomeningitis virus (lcmv) infection. mice were electroporated with plasmids expressing a variety of pro- or anti-apoptotic molecules related to fas signaling and then either lcmv-infected or injected with plasmid dna expressing siv or hiv antigens. where ...	2015	25807052
a ceramide analogue stimulates dendritic cells to promote t cell responses upon virus infections.	the ceramide family of lipids plays important roles in both cell structure and signaling in a diverse array of cell types, including immune cells. however, very little is known regarding how ceramide affects the activation of dendritic cells (dcs) in response to viral infection. in this study, we demonstrate that a synthetic ceramide analog (c8) stimulates dcs to increase the expansion of virus-specific t cells upon virus infection. exogenously supplied c8 ceramide elevated the expression of dc ...	2015	25810392
novel mechanism of arenavirus-induced liver pathology.	viral hemorrhagic fevers (vhfs) encompass a group of diseases with cardinal symptoms of fever, hemorrhage, and shock. the liver is a critical mediator of vhf disease pathogenesis and high levels of alt/ast transaminases in plasma correlate with poor prognosis. in fact, lassa fever (lf), the most prevalent vhf in africa, was initially clinically described as hepatitis. previous studies in non-human primate (nhp) models also correlated lf pathogenesis with a robust proliferative response in the li ...	2015	25822203
t cell lipid peroxidation induces ferroptosis and prevents immunity to infection.	the selenoenzyme glutathione peroxidase 4 (gpx4) is a major scavenger of phospholipid hydroperoxides. although gpx4 represents a key component of the reactive oxygen species-scavenging network, its relevance in the immune system is yet to be defined. here, we investigated the importance of gpx4 for physiological t cell responses by using t cell-specific gpx4-deficient mice. our results revealed that, despite normal thymic t cell development, cd8(+) t cells from t(δgpx4/δgpx4) mice had an intrins ...	2015	25824823
t-bet- and stat4-dependent il-33 receptor expression directly promotes antiviral th1 cell responses.	during infection, the release of damage-associated molecular patterns, so-called "alarmins," orchestrates the immune response. the alarmin il-33 plays a role in a wide range of pathologies. upon release, il-33 signals through its receptor st2, which reportedly is expressed only on cd4(+) t cells of the th2 and regulatory subsets. here we show that th1 effector cells also express st2 upon differentiation in vitro and in vivo during lymphocytic choriomeningitis virus (lcmv) infection. the expressi ...	2015	25829541
antiviral effect of interferon lambda against lymphocytic choriomeningitis virus.	lambda interferons inhibit replication of many viruses, but their role in the inhibition of lymphocytic choriomeningitis virus (lcmv) infection remains unclear. in this study, we examined the antiviral effects of interferon (ifn)-λ2 and ifn-λ3 against lcmv in a549 cells. we found that ifn-λ2 is a more potent inhibitor of lcmv strain mx compared with ifn-λ3, whereas both cytokines have similar antiviral effects against an immunosuppressive variant of lcmv, clone-13. we also demonstrated that the ...	2015	25830339
lymphocytic choriomeningitis virus differentially affects the virus-induced type i interferon response and mitochondrial apoptosis mediated by rig-i/mavs.	arenaviruses are important emerging human pathogens maintained by noncytolytic persistent infection in their rodent reservoir hosts. despite high levels of viral replication, persistently infected carrier hosts show only mildly elevated levels of type i interferon (ifn-i). accordingly, the arenavirus nucleoprotein (np) has been identified as a potent ifn-i antagonist capable of blocking activation of interferon regulatory factor 3 (irf3) via the retinoic acid inducible gene (rig)-i/mitochondrial ...	2015	25833049
evaluation of non-reciprocal heterologous immunity between unrelated viruses.	heterologous immunity refers to the phenomenon whereby a history of an immune response against one pathogen can provide a level of immunity to a second unrelated pathogen. previous investigations have shown that heterologous immunity is not necessarily reciprocal, such as in the case of vaccinia virus (vacv). replication of vacv is reduced in mice immune to a variety of pathogens, while vacv fails to induce immunity to several of the same pathogens, including lymphocytic choriomeningitis virus ( ...	2015	25838115
lassa-vesicular stomatitis chimeric virus safely destroys brain tumors.	high-grade tumors in the brain are among the deadliest of cancers. here, we took a promising oncolytic virus, vesicular stomatitis virus (vsv), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic vsv glycoprotein with the glycoprotein from one of five different viruses, including ebola virus, marburg virus, lymphocytic choriomeningitis virus (lcmv), rabies virus, and lass ...	2015	25878115
t cell metabolism. the protein lem promotes cd8⁺ t cell immunity through effects on mitochondrial respiration.	protective cd8(+) t cell-mediated immunity requires a massive expansion in cell number and the development of long-lived memory cells. using forward genetics in mice, we identified an orphan protein named lymphocyte expansion molecule (lem) that promoted antigen-dependent cd8(+) t cell proliferation, effector function, and memory cell generation in response to infection with lymphocytic choriomeningitis virus. generation of lem-deficient mice confirmed these results. through interaction with cr6 ...	2015	25883318
single nucleoprotein residue modulates arenavirus replication complex formation.	the arenaviridae are enveloped, negative-sense rna viruses with several family members that cause hemorrhagic fevers. this work provides immunofluorescence evidence that, unlike those of new world arenaviruses, the replication and transcription complexes (rtc) of lymphocytic choriomeningitis virus (lcmv) colocalize with eukaryotic initiation factor 4e (eif4e) and that eif4e may participate in the translation of lcmv mrna. additionally, we identify two residues in the lcmv nucleoprotein (np) that ...	2015	25922393
estimating the in vivo killing efficacy of cytotoxic t lymphocytes across different peptide-mhc complex densities.	cytotoxic t lymphocytes (ctls) are important agents in the control of intracellular pathogens, which specifically recognize and kill infected cells. recently developed experimental methods allow the estimation of the ctl's efficacy in detecting and clearing infected host cells. one method, the in vivo killing assay, utilizes the adoptive transfer of antigen displaying target cells into the bloodstream of mice. surprisingly, killing efficacies measured by this method are often much higher than es ...	2015	25933039
pd-1 upregulated on regulatory t cells during chronic virus infection enhances the suppression of cd8+ t cell immune response via the interaction with pd-l1 expressed on cd8+ t cells.	regulatory t (treg) cells act as terminators of t cell immuniy during acute phase of viral infection; however, their role and suppressive mechanism in chronic viral infection are not completely understood. in this study, we compared the phenotype and function of treg cells during acute or chronic infection with lymphocytic choriomeningitis virus. chronic infection, unlike acute infection, led to a large expansion of treg cells and their upregulation of programmed death-1 (pd-1). treg cells from ...	2015	25934860
cutting edge: t follicular helper cell differentiation is defective in the absence of bcl6 btb repressor domain function.	t follicular helper (tfh) cells are essential for germinal centers (gcs) and most long-term humoral immunity. differentiation of tfh cells depends on the transcriptional repressor b cell cll/lymphoma 6 (bcl6). bcl6 mediates gene repression via the recruitment of corepressors. currently, it is unknown how bcl6 recruits corepressors to regulate gene expression of tfh cells. in this article, we demonstrate, using a mutant form of bcl6 with two btb (bric-a-brac, tramtrack, broad-complex) mutations t ...	2015	25957170
arenavirus genome rearrangement for the development of live attenuated vaccines.	several members of the arenaviridae family cause hemorrhagic fever disease in humans and pose serious public health problems in their geographic regions of endemicity as well as a credible biodefense threat. to date, there have been no fda-approved arenavirus vaccines, and current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. arenaviruses are enveloped viruses with a bisegmented negative-stranded rna genome. each genome segment uses an ambis ...	2015	25972555