Publications

interferon-gamma acts directly on cd8+ t cells to increase their abundance during virus infection.	interferon-gamma (ifngamma) is important in regulating the adaptive immune response, and most current evidence suggests that it exerts a negative (proapoptotic) effect on cd8(+) t cell responses. we have developed a novel technique of dual adoptive transfer, which allowed us to precisely compare, in normal mice, the in vivo antiviral responses of two t cell populations that differ only in their expression of the ifngamma receptor. we use this technique to show that, contrary to expectations, ifn ...	2005	15809350
evaluating the immunogenicity and protective efficacy of a dna vaccine encoding lassa virus nucleoprotein.	several viruses in the arenavirus genus of the family arenaviridae cause severe, often fatal, hemorrhagic fever. one such virus, lassa virus (lv), is a frequent cause of disease in africa, and survivors often are left with substantial neurological impairment. the feasibility of protective immunization against lv infection, and the associated disease, has been demonstrated in animal models, using recombinant vaccinia viruses to deliver lassa proteins. circumstantial evidence implicates cellular i ...	2005	15823608
cytosolic delivery of viral nucleoprotein by listeriolysin o-liposome induces enhanced specific cytotoxic t lymphocyte response and protective immunity.	cytotoxic t lymphocytes (ctls) are capable of conferring protection against intracellular pathogens and tumor. protective antiviral immunity, mediated by the activation of antigenic epitope-specific ctl, can be achieved by delivering exogenous antigen into the cytosol of antigen-presenting cells. cytosolic introduction of vaccine antigen, however, requires a specialized delivery strategy due to the membrane barrier limiting the access of macromolecules to the cytosol. in this study, we have inve ...	2004	15832496
serological study of the lymphochoriomeningitis virus (lcmv) in an inner city of argentina.	lymphocytic choriomeningitis virus (lcmv) is the prototype of the family arenaviridae and is associated with the natural reservoir, mus domesticus (md). it causes meningitis and a flu-like illness characterized by malaise, myalgia, retrorbital headache, and photophobia. this study presents the data obtained in a rodent and human serological study during 6 years (1998-2003) in the city of rio cuarto, argentina. antibodies anti-lcmv were sought by elisa in rodents and humans. lcmv was found only i ...	2005	15834871
reducing the stimulation of cd8+ t cells during infection with intracellular bacteria promotes differentiation primarily into a central (cd62lhighcd44high) subset.	during infection with lymphocytic choriomeningitis virus, cd8(+) t cells differentiate rapidly into effectors (cd62l(low)cd44(high)) that differentiate further into the central memory phenotype (cd62l(high)cd44(high)) gradually. to evaluate whether this cd8(+) t cell differentiation program operates in all infection models, we evaluated cd8(+) t cell differentiation during infection of mice with recombinant intracellular bacteria, listeria monocytogenes (lm) and mycobacterium bovis (bcg), expres ...	2005	15843531
a structural basis for cd8+ t cell-dependent recognition of non-homologous peptide ligands: implications for molecular mimicry in autoreactivity.	molecular mimicry of self-epitopes by viral antigens is one possible pathogenic mechanism underlying induction of autoimmunity. a self-epitope, mdbm, derived from mouse dopamine beta-mono-oxygenase (kalydyapi) sharing 44% sequence identity with the lymphocytic choriomeningitis virus-derived immunodominant epitope gp33 (kavynfatc/m), has previously been identified as a cross-reactive self-ligand, presentation of which results in autoimmunity. a rat peptide homologue, rdbm (kalynyapi, 56% identity ...	2005	15845547
limited in vivo reactivity of polyclonal effector cytotoxic t cells towards altered peptide ligands.	t cell responses are regulated by the affinity/avidity of the t cell receptor for the mhc/peptide complex, available costimulation and duration of antigenic stimulation. altered peptide ligands (apls) are usually recognized with a reduced affinity/avidity by the t cell receptor and are often able to only partially activate t cells in vitro or may even function as antagonists. here we assessed the ability of apls derived from peptide p33 of lymphocytic choriomeningitis virus (lcmv) to mediate lys ...	2005	15857805
characterization of the interaction of lassa fever virus with its cellular receptor alpha-dystroglycan.	the cellular receptor for the old world arenaviruses lassa fever virus (lfv) and lymphocytic choriomeningitis virus (lcmv) has recently been identified as alpha-dystroglycan (alpha-dg), a cell surface receptor that provides a molecular link between the extracellular matrix and the actin-based cytoskeleton. in the present study, we show that lfv binds to alpha-dg with high affinity in the low-nanomolar range. recombinant vesicular stomatitis virus pseudotyped with lfv glycoprotein (gp) adopted th ...	2005	15857984
cutting edge: emergence of cd127high functionally competent memory t cells is compromised by high viral loads and inadequate t cell help.	in this report we have inspected whether difficulties in controlling viral infections negatively impacts the generation of cd127(high) memory t cells. using both mhc class i and ii tetramers we reveal that cd127(low) t cells are not necessarily rapidly deleted but can persist in a pseudoeffector state in which they display the hallmarks of activated effector cells but are functionally inferior. cd127(high) cells can, however, emerge if the infection is contained. we also show that in the absence ...	2005	15879083
cutting edge: re-evaluating the in vivo cytokine responses of cd8+ t cells during primary and secondary viral infections.	virus-specific cd8(+) t cells produce ifn-gamma after ag contact and, in the absence of this cytokine, the host often cannot eradicate infection. however, our ability to identify cells that are actively expressing this critical effector function in vivo is limited, because the protein is rapidly secreted. in this study, we describe a simple approach that circumvents the need for ex vivo ag stimulation and allows the enumeration of cd8(+) t cells that are actively synthesizing ifn-gamma in vivo d ...	2005	15879085
genetic and biochemical evidence for an oligomeric structure of the functional l polymerase of the prototypic arenavirus lymphocytic choriomeningitis virus.	the arenavirus l protein has the characteristic sequence motifs conserved among the rna-dependent rna polymerase l proteins of negative-strand (ns) rna viruses. studies based on the use of reverse-genetics approaches have provided direct experimental evidence of the key role played by the arenavirus l protein in viral-rna synthesis. sequence alignment shows six conserved domains among l proteins of ns rna viruses. the proposed polymerase module of l is located within its domain iii, which contai ...	2005	15890965
rapid conversion of effector mechanisms from nk to t cells during virus-induced lysis of allogeneic implants in vivo.	viral infections can strongly stimulate both nk cell and allospecific cd8 t cell responses, and these same effector cells can lyse allogeneic cell lines in vitro. however, the impact of viral infections on the effector systems mediating rejection of allogeneic tissues in vivo has not been fully explored. using in vivo cytotoxicity assays, we evaluated the effector systems mediating the rejection of cfse-labeled allogeneic splenocytes after an infection of c57bl/6 (b6) mice with lymphocytic chori ...	2005	15905505
differential regulation of interferon regulatory factor (irf)-7 and irf-9 gene expression in the central nervous system during viral infection.	interferon regulatory factors (irfs) are a family of transcription factors involved in the regulation of the interferons (ifns) and other genes that may have an essential role in antiviral defense in the central nervous system, although this is currently not well defined. therefore, we examined the regulation of irf gene expression in the brain during viral infection. several irf genes (irf-2, -3, -5, -7, and -9) were expressed at low levels in the brain of uninfected mice. following intracrania ...	2005	15919906
lymphocytic choriomeningitis virus infection in organ transplant recipients--massachusetts, rhode island, 2005.	on may 3, 2005, cdc received a report of severe illness in four patients who had received solid organ transplants from a common donor. all four organ recipients subsequently were found to have evidence of infection with lymphocytic choriomeningitis virus (lcmv), a rodent-borne old world arenavirus. preliminary findings from the ensuing investigation indicate the source of infection likely was an infected hamster in the donor's home. this report summarizes the ongoing investigation and provides i ...	2005	15931158
rapid destruction of the tumor microenvironment by ctls recognizing cancer-specific antigens cross-presented by stromal cells.	a single tumor contains a heterogeneous population of cancer cells. some cancer cells express antigens and are susceptible to specific ctls. however, other cancer cells are antigen-loss variants (alvs) that escape these ctls because they express little or no antigen. here, we show that antigen-specific t cells can eliminate alvs when the parental population expresses a model gp33 antigen (kavynfatm) at a level sufficient to be locally cross-presented by the nonmalignant stromal cells. that is, t ...	2005	15934727
in vivo modulation of t cell responses and protective immunity by tcr antagonism during infection.	infectious agents are known to express altered peptide ligands that antagonize t cells in vitro; however, direct evidence of tcr antagonism during infection is still lacking, and its importance in the context of infection remains to be established. in this study, we used a murine model of infection with recombinant listeria monocytogenes and addressed three issues that are critical for assessing the role of tcr antagonism in the modulation of the immune response. first, we demonstrated that the ...	2005	15944303
il-7 receptor alpha chain expression distinguishes functional subsets of virus-specific human cd8+ t cells.	virus-specific cd8+ t cells emerge after infection with herpesviruses and maintain latency to these persistent pathogens. it has been demonstrated that murine memory cd8+ t-cell precursors specific for acute lymphocytic choriomeningitis virus express interleukin-7 receptor alpha (il-7ralpha), and il-7 is involved in maintaining memory populations after the clearance of antigen. to investigate whether human cd8+ t cells reactive toward persistent viruses are maintained similarly, we analyzed il-7 ...	2005	15947093
innate stat1-dependent genomic response of neurons to the antiviral cytokine alpha interferon.	alpha/beta interferons (ifns-alpha/beta) are cytokines that play an essential role in the host defense against viral infection. our previous studies have shown that the key ifn signaling molecule stat1 is highly elevated and activated in central nervous system neurons during viral infection and in transgenic mice with astrocyte production of ifn-alpha (glial fibrillary acidic protein [gfap]-ifn-alpha), suggesting that neurons are a very responsive target cell population for ifns. to elucidate th ...	2005	15956575
how viral infections affect the autoimmune process leading to type 1 diabetes.	despite a large body of evidence describing associations between viruses and the development of type 1 diabetes (t1d) in genetically prone individuals, clearly defining causative infectious agents has not been successful. a likely explanation is that the link between infections and autoimmunity is more multifaceted than we initially assumed. viral footprints might be hard to detect systemically or in the target organ once autoimmunity has been initiated, and several infections might have to act ...	2005	15963965
cd8alpha+ dendritic cells selectively present mhc class i-restricted noncytolytic viral and intracellular bacterial antigens in vivo.	cd8alpha(+) dendritic cells (dcs) have been shown to be the principal dc subset involved in priming mhc class i-restricted ctl immunity to a variety of cytolytic viruses, including hsv type 1, influenza, and vaccinia virus. whether priming of ctls by cd8alpha(+) dcs is limited to cytolytic viruses, which may provide dead cellular material for this dc subset, or whether these dcs selectively present intracellular ags, is unknown. to address this question, we examined ag presentation to a noncytol ...	2005	15972648
low cd8 t-cell proliferative potential and high viral load limit the effectiveness of therapeutic vaccination.	therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. however, many therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral t-cell responses is not always observed. to examine these issues, we studied the impact of therapeutic vaccination, using a murine model of chronic infection with lymphocytic choriomeningitis virus (lcmv). our results demonstrate that therapeutic vaccination ...	2005	15994790
cross-presentation of the long-lived lymphocytic choriomeningitis virus nucleoprotein does not require neosynthesis and is enhanced via heat shock proteins.	many viral proteins that contain mhc class i-restricted peptides are long-lived, and it is elusive how they can give rise to class i epitopes. recently, we showed that direct presentation of an epitope of the long-lived lymphocytic choriomeningitis virus nucleoprotein (lcmv-np) required neosynthesis in accordance with the defective ribosomal products hypothesis. in this study, we report that lcmv-np can be cross-primed in mice using either lcmv-np-transfected human hek293 or balb/c-derived b8 ce ...	2005	16002676
immunoproteasome-deficient mice mount largely normal cd8+ t cell responses to lymphocytic choriomeningitis virus infection and dna vaccination.	during viral infection, constitutive proteasomes are largely replaced by immunoproteasomes, which display distinct cleavage specificities, resulting in different populations of potential cd8(+) t cell epitope peptides. immunoproteasomes are believed to be important for the generation of many viral cd8(+) t cell epitopes and have been implicated in shaping the immunodominance hierarchies of cd8(+) t cell responses to influenza virus infection. however, it remains unclear whether these conclusions ...	2005	16002717
role of thymic output in regulating cd8 t-cell homeostasis during acute and chronic viral infection.	although it is well documented that cd8 t cells play a critical role in controlling chronic viral infections, the mechanisms underlying the regulation of cd8 t-cell responses are not well understood. using the mouse model of an acute and chronic lymphocytic choriomeningitis virus (lcmv) infection, we have examined the relative importance of peripheral t cells and thymic emigrants in the elicitation and maintenance of cd8 t-cell responses. virus-specific cd8 t-cell responses were compared between ...	2005	16014905
inhibition, escape, and attenuated growth of severe acute respiratory syndrome coronavirus treated with antisense morpholino oligomers.	the recently emerged severe acute respiratory syndrome coronavirus (sars-cov) is a potent pathogen of humans and is capable of rapid global spread. peptide-conjugated antisense morpholino oligomers (p-pmo) were designed to bind by base pairing to specific sequences in the sars-cov (tor2 strain) genome. the p-pmo were tested for their capacity to inhibit production of infectious virus as well as to probe the function of conserved viral rna motifs and secondary structures. several virus-targeted p ...	2005	16014928
impaired virus control and severe cd8+ t-cell-mediated immunopathology in chimeric mice deficient in gamma interferon receptor expression on both parenchymal and hematopoietic cells.	bone marrow chimeras were used to determine the cellular target(s) for the antiviral activity of gamma interferon (ifn-gamma). by transfusing such mice with high numbers of naive virus-specific cd8(+) t cells, a system was created in which the majority of virus-specific cd8(+) t cells would be capable of responding to ifn-gamma, but expression of the relevant receptor on non-t cells could be experimentally controlled. only when the ifn-gamma receptor is absent on both radioresistant parenchymal ...	2005	16014969
isg15, an interferon-stimulated ubiquitin-like protein, is not essential for stat1 signaling and responses against vesicular stomatitis and lymphocytic choriomeningitis virus.	isg15 is an interferon-induced ubiquitin-like modifier which can be conjugated to distinct, but largely unknown, proteins. isg15 has been implicated in a variety of biological activities, which encompass antiviral defense, immune responses, and pregnancy. mice lacking ubp43 (usp18), the isg15-deconjugating enzyme, develop a severe phenotype with brain injuries and lethal hypersensitivity to poly(i:c). it has been reported that an augmented conjugation of isg15 in the absence of ubp43 induces pro ...	2005	16024773
opposing effects of cxcr3 and ccr5 deficiency on cd8+ t cell-mediated inflammation in the central nervous system of virus-infected mice.	t cells play a key role in the control of viral infection in the cns but may also contribute to immune-mediated cell damage. to study the redundancy of the chemokine receptors cxcr3 and ccr5 in regulating virus-induced cd8+ t cell-mediated inflammation in the brain, cxcr3/ccr5 double-deficient mice were generated and infected intracerebrally with noncytolytic lymphocytic choriomeningitis virus. because these chemokine receptors are mostly expressed by overlapping subsets of activated cd8+ t cell ...	2005	16034118
mutagenesis-induced, large fitness variations with an invariant arenavirus consensus genomic nucleotide sequence.	enhanced mutagenesis may result in rna virus extinction, but the molecular events underlying this process are not well understood. here we show that 5-fluorouracil (fu)-induced mutagenesis of the arenavirus lymphocytic choriomeningitis virus (lcmv) resulted in preextinction populations whose consensus genomic nucleotide sequence remained unaltered. furthermore, fitness recovery passages in the absence of fu, or alternate virus passages in the presence and absence of fu, led to profound differenc ...	2005	16051837
intrinsic functional dysregulation of cd4 t cells occurs rapidly following persistent viral infection.	effective t-cell responses are critical to eradicate acute viral infections and prevent viral persistence. emerging evidence indicates that robust, early cd4 t-cell responses are important in effectively sustaining cd8 t-cell activity. herein, we illustrate that virus-specific cd4 t cells are functionally inactivated early during the transition into viral persistence and fail to produce effector cytokines (i.e., interleukin-2 and tumor necrosis factor alpha), thereby compromising an efficient an ...	2005	16051844
interim guidance for minimizing risk for human lymphocytic choriomeningitis virus infection associated with rodents.	in may 2005, cdc received reports of four organ-transplant recipients with unknown illness. all were discovered to have been infected with lymphocytic choriomeningitis virus (lcmv) via a common organ donor. epidemiologic investigation traced the source of the virus to a pet hamster purchased by the donor from a local pet store. lcmv testing of other rodents at the pet store revealed three other lcmv-infected rodents (two hamsters and a guinea pig), supplied by a single distributor (distributor a ...	2005	16079740
rna interference-mediated virus clearance from cells both acutely and chronically infected with the prototypic arenavirus lymphocytic choriomeningitis virus.	several arenaviruses, including lassa fever virus, cause severe, often lethal hemorrhagic fever in humans. no licensed vaccines are available in the united states, and currently there is no efficacious therapy to treat this viral infection. therefore the importance of developing effective antiviral approaches to combat pathogenic arenaviruses is clear. moreover, the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) is an important model for the study of viral persistence and associ ...	2005	16103158
update: interim guidance for minimizing risk for human lymphocytic choriomeningitis virus infection associated with pet rodents.	in may 2005, cdc received reports of illness in four solid-organ transplant recipients who were later determined to have been infected with lymphocytic choriomeningitis virus (lcmv) from a common organ donor. three of the four organ recipients died, 23-27 days after transplantation. this report updates information about the ongoing investigation and provides interim measures for reducing the risk for lcmv infection from pet rodents associated with this outbreak.	2005	16107785
in vivo generation of pathogen-specific th1 cells in the absence of the ifn-gamma receptor.	the precise mechanisms that govern the commitment of cd4 t cells to become th1 or th2 cells in vivo are incompletely understood. recent experiments demonstrate colocalization of the ifn-gammar chains with the tcr during activation of naive cd4 t cells, suggesting that association of these molecules may be involved in determining lineage commitment. to test the role of ifn-gamma and its receptor in the generation of th1 ag-specific cd4 t cells, we analyzed mice after infection with listeria monoc ...	2005	16116201
immunomodulatory dendritic cells require autologous serum to circumvent nonspecific immunosuppressive activity in vivo.	in immunotherapy, dendritic cells (dcs) can be used as powerful antigen-presenting cells to enhance or suppress antigen-specific immunity upon in vivo transfer in mice or humans. however, to generate sufficient numbers of dcs, most protocols include an ex vivo culture step, wherein the cells are exposed to heterologous serum and/or antigenic stimuli. in mouse models of virus infection and virus-induced autoimmunity, we tested how heterologous serum affects the immunomodulatory capacity of immatu ...	2005	16118326
type i interferons act directly on cd8 t cells to allow clonal expansion and memory formation in response to viral infection.	t cell expansion and memory formation are generally more effective when elicited by live organisms than by inactivated vaccines. elucidation of the underlying mechanisms is important for vaccination and therapeutic strategies. we show that the massive expansion of antigen-specific cd8 t cells that occurs in response to viral infection is critically dependent on the direct action of type i interferons (ifn-is) on cd8 t cells. by examining the response to infection with lymphocytic choriomeningiti ...	2005	16129706
increased expression of the nk cell receptor klrg1 by virus-specific cd8 t cells during persistent antigen stimulation.	the killer cell lectin-like receptor g1 (klrg1) is a natural killer cell receptor expressed by t cells that exhibit impaired proliferative capacity. here, we determined the klrg1 expression by virus-specific t cells. we found that repetitive and persistent antigen stimulation leads to an increase in klrg1 expression of virus-specific cd8+ t cells in mice and that virus-specific cd8+ t cells are mostly klrg1+ in chronic human viral infections (human immunodeficiency virus, cytomegalovirus, and ep ...	2005	16140789
islet-specific expression of cxcl10 causes spontaneous islet infiltration and accelerates diabetes development.	during inflammation, chemokines are conductors of lymphocyte trafficking. the chemokine cxcl10 is expressed early after virus infection. in a virus-induced mouse model for type 1 diabetes, cxcl10 blockade abrogated disease by interfering with trafficking of autoaggressive lymphocytes to the pancreas. we have generated transgenic rat insulin promotor (rip)-cxcl10 mice expressing cxcl10 in the beta cells of the islets of langerhans to evaluate how bystander inflammation influences autoimmunity. ri ...	2005	16148094
virus-induced inhibition of cd1d1-mediated antigen presentation: reciprocal regulation by p38 and erk.	a critical component of the host's innate immune response involves lipid ag presentation by cd1d molecules to nk t cells. in this study we used murine cd1d1-transfected l (l-cd1) cells to study the effect of viruses on cd1d-mediated ag presentation to nkt cells and found that an infection with vesicular stomatitis and vaccinia (but not lymphocytic choriomeningitis) virus inhibited murine cd1d1-mediated ag presentation. this was under the reciprocal control of the mapks, p38 and erk, and was due ...	2005	16177070
recall proliferation potential of memory cd8+ t cells and antiviral protection.	memory cd8+ t cells play a crucial role in mediating protection from infection with viruses and other intracellular pathogens. memory t cells are not a homogenous cellular population and may be separated into central memory t cells with substantial recall proliferation capacity and effector memory t cells with limited recall proliferation capacity. it has been suggested that the protective capacity of effector memory t cells is more limited than that of central memory t cells in viral infections ...	2005	16177115
functional properties and lineage relationship of cd8+ t cell subsets identified by expression of il-7 receptor alpha and cd62l.	three major subsets of ag-experienced cd8+ t cells have been identified according to their expression of cd62l and cd127. these markers are associated with central memory t cells (cd62l+ cd127+), effector memory t cells (cd162l- cd127+), and effector t cells (cd62l- cd127-). in this study we characterized the development of these three populations during acute and chronic viral infections and after immunization with virus-like particles and determined their lineage relation and functional and pr ...	2005	16177116
innate signals compensate for the absence of pkc-{theta} during in vivo cd8(+) t cell effector and memory responses.	pkc- is central to t-helper (th) 2 cell differentiation and effector function; however, its importance for antiviral effector, and in particular memory cd8(+) t cell responses, remains unclear. we have investigated the role of pkc- during in vivo and in vitro responses against influenza virus, lymphocytic choriomeningitis virus, vaccinia virus, and replication-deficient virus-like particles. in the absence of pkc-, antiviral cd8(+) t cells presented an unresponsive phenotype in vitro, which coul ...	2005	16186501
rapid recruitment of virus-specific cd8 t cells restructures immunodominance during protective secondary responses.	in this study we investigate the attributes of virus-specific memory cd8 t cells which most effectively control secondary infections. by rechallenging mice that had cleared primary lymphocytic choriomeningitis virus infections, we revealed that the secondary response is remarkably swift. within 6 h following secondary infection, the production of gamma interferon becomes detectable directly ex vivo. during this protective phase of the secondary response, a very early elaboration of effector acti ...	2005	16188973
development of multiplex pcrs for detection of common viral pathogens and agents of congenital infections.	potential causes of congenital infection include toxoplasma gondii and viruses such as cytomegalovirus (cmv), enterovirus, hepatitis c virus, herpes simplex virus types 1 and 2 (hsv-1 and -2), human herpesvirus types 6, 7, and 8, lymphocytic choriomeningitis virus, parvovirus, rubella virus, and varicella-zoster virus. testing for each of these agents using nucleic acid tests is time consuming and the availability of clinical samples such as amniotic fluid or neonatal blood is often limited. the ...	2005	16207970
rapid production of tnf-alpha following tcr engagement of naive cd8 t cells.	the acquisition of effector functions by naive cd8 t cells following tcr engagement is thought to occur sequentially with full functionality being gained only after the initiation of division. we show that naive cd8 t cells are capable of immediate effector function following tcr engagement, which stimulates the rapid production of tnf-alpha. stimulation of splenocytes from naive mice of differing genetic backgrounds with anti-cd3epsilon mab resulted in significant production of tnf-alpha by nai ...	2005	16210607
requirement for neutralizing antibodies to control bone marrow transplantation-associated persistent viral infection and to reduce immunopathology.	bone marrow transplantation (bmt) is commonly used in the treatment of leukemia, however its therapeutic application is partly limited by the high incidence of associated opportunistic infections. we modeled this clinical situation by infecting mice that underwent bmt with lymphocytic choriomeningitis virus (lcmv) and investigated the potential of immunotherapeutic strategies to counter such infections. all mice that received bmt survived lcmv infection and developed a virus carrier status. immu ...	2005	16210661
critical role for dna vaccination frequency in induction of antigen-specific cytotoxic responses.	since antigen-persistence plays a role for induction of immunity, we investigated the in vivo pharmacokinetic of a naked dna vaccine at the site of its action, i.e., in the lymph node. after direct intralymphatic injection, naked dna vaccine degraded within a few hours. in correlation with the short persistence of the dna vaccine we found that the frequency of vaccination critically influenced the strength of the immune response. in mice vaccinated every 3 days, cytotoxic t-cell responses were e ...	2006	16225968
cd8 alpha alpha homodimer expression and role in cd8 t cell memory generation during influenza virus a infection in mice.	while the precise function of cd8alphaalpha homodimer expression on peripheral t cells is uncertain, recent evidence indicates that it facilitates survival and differentiation of lymphocytic choriomeningitis virus (lcmv)-specific memory cd8alphabeta t cell precursors in vivo. here, we show that the cd8alphaalpha homodimer is also transiently up-regulated on influenza a virus-specific cd8alphabeta t cells after infection in vivo, temporally correlating with increased levels of the memory t cell d ...	2005	16231286
virus-induced polyclonal b cell activation improves protective ctl memory via retained cd27 expression on memory ctl.	different viruses elicit distinct phenotypes of memory cytotoxic t lymphocytes (ctl). this is reflected in differential expression of homing receptors and costimulatory molecules like cd27. memory ctl retained cd27 following lymphocytic choriomeningitis virus (lcmv) infection, but not after immunization with recombinant vaccinia virus or tumor cells expressing lcmv glycoprotein. stable cd27 expression on memory ctl required ligation by cd70 expressed on polyclonally activated b cells during the ...	2005	16231287
cutting edge: early ifn-gamma signaling directly enhances primary antiviral cd4+ t cell responses.	ifn-gamma drives cd4+ t cell differentiation toward the th1 phenotype (th1) and suppresses th2 development. current evidence indicates that ifn-gamma inhibits t cell proliferation and decreases t cell survival. in contrast to the above, we show here that antiviral cd4+ t cell generation after infection is reduced in the absence of ifn-gamma signals. the deficient expansion of cells was not due to perturbations in t cell sensitivity to peptide or to altered migratory patterns through nonlymphoid ...	2005	16237051
lymphocytic choriomeningitis virus.		2005	16247097
a live attenuated vaccine for lassa fever made by reassortment of lassa and mopeia viruses.	lassa virus (lasv) and mopeia virus (mopv) are closely related old world arenaviruses that can exchange genomic segments (reassort) during coinfection. clone ml29, selected from a library of mopv/lasv (mop/las) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of lasv and the rna polymerase and zinc-binding protein of mopv. replication of ml29 was attenuated in guinea pigs and nonhuman primates. in murine adoptive-transfer experiments, as little as 150 pfu of ml29 induced ...	2005	16254329
posttranslational modification of alpha-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase large is critical for virus binding.	the receptor for lymphocytic choriomeningitis virus (lcmv), the human pathogenic lassa fever virus (lfv), and clade c new world arenaviruses is alpha-dystroglycan (alpha-dg), a cell surface receptor for proteins of the extracellular matrix (ecm). specific posttranslational modification of alpha-dg by the glycosyltransferase large is critical for its function as an ecm receptor. in the present study, we show that large-dependent modification is also crucial for alpha-dg's function as a cellular r ...	2005	16254363
o mannosylation of alpha-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function.	alpha-dystroglycan (alpha-dg) was identified as a common receptor for lymphocytic choriomeningitis virus (lcmv) and several other arenaviruses including the human pathogenic lassa fever virus. initial work postulated that interactions between arenavirus glycoproteins and alpha-dg are based on protein-protein interactions. we found, however, that susceptibility toward lcmv infection differed in various cell lines despite them expressing comparable levels of dg, suggesting that posttranslational m ...	2005	16254364
a role for dual viral hits in causation of subacute sclerosing panencephalitis.	subacute sclerosing panencephalitis (sspe) is a progressive fatal neurodegenerative disease associated with persistent infection of the central nervous system (cns) by measles virus (mv), biased hypermutations of the viral genome affecting primarily the matrix (m) gene with the conversion of u to c and a to g bases, high titers of antibodies to mv, and infiltration of b cells and t cells into the cns. neither the precipitating event nor biology underlying the mv infection is understood, nor is t ...	2005	16260490
reciprocal immunomodulation in a schistosome and hepatotropic virus coinfection model.	human coinfection with the helminth parasite schistosoma mansoni and hepatitis b and hepatitis c viruses is associated with increased hepatic viral burdens and severe liver pathology. in this study we developed a murine s. mansoni/lymphocytic choriomeningitis virus (lcmv) coinfection model that reproduces the enhanced viral replication and liver pathology observed in human coinfections, and used this model to explore the mechanisms involved. viral coinfection during the th2-dominated granulomato ...	2005	16272278
leucine aminopeptidase is not essential for trimming peptides in the cytosol or generating epitopes for mhc class i antigen presentation.	to detect viral infections and tumors, cd8+ t lymphocytes monitor cells for the presence of antigenic peptides bound to mhc class i molecules. the majority of mhc class i-presented peptides are generated from the cleavage of cellular and viral proteins by the ubiquitin-proteasome pathway. many of the oligopeptides produced by this process are too long to stably bind to mhc class i molecules and require further trimming for presentation. leucine aminopeptidase (lap) is an ifn-inducible cytosolic ...	2005	16272315
cutting edge: murine cd59a modulates antiviral cd4+ t cell activity in a complement-independent manner.	cd59 blocks formation of the membrane attack complex of complement by inhibiting binding of c9 to the c5b-8 complex. to investigate a role for cd59 in promoting t cell responses, we compared t cell activation in cd59a-deficient (cd59a-/-) and wild-type (wt) mice after in vitro stimulation and after infection with rvv. virus-specific cd4+ t cell responses were significantly enhanced in cd59a-/- mice compared with wt mice. similarly, cd59a-/- t cells responded more vigorously to in vitro stimulati ...	2005	16301611
reexamination of the role of ubiquitin-like modifier isg15 in the phenotype of ubp43-deficient mice.	ubp43/usp18 was described as a specific protease that removes conjugated ubiquitin-like modifier isg15 from target proteins. the severe phenotype of ubp43(-/-) mice characterized by premature death, brain cell injury, and deregulated stat1 signaling was ascribed to an enhanced conjugation of isg15. in contrast, no phenotypic changes were detected in isg15(-/-) mice. to verify the role of isg15 in the phenotype of ubp43(-/-) mice, we employed mice deficient for both isg15 and ubp43. here, we show ...	2005	16314524
molecular and cellular mechanisms, pathogenesis, and treatment of insulin-dependent diabetes obtained through study of a transgenic model of molecular mimicry.	the portrait of autoimmune diabetes mellitus or type i diabetes can be copied by a transgenic model in which either the nucleoprotein (np) or glycoprotein (gp) of lymphocytic choriomeningitis virus (lcmv) is expressed in beta cells of the islets of langerhans. in the absence of further environmental insult, diabetes does not occur. however, when lcmv or a dissimilar virus that shares cross-reactive t cell epitopes with lcmv initiates infection, diabetes ensues. if the self "viral" transgene is e ...	2005	16329191
distinct host-dependent pathogenic mechanisms leading to a similar clinical anemia after infection with lymphocytic choriomeningitis virus.	the docile strain of lymphocytic choriomeningitis virus (lcmv) induces anemia in a number of inbred strains of mice, including c3heb/fej and cba/ht animals. a difference in the kinetics of anemia and in compensatory reticulocytosis suggested that impaired erythropoiesis was the major pathogenic mechanism involved in cba/ht mice, but not in c3heb/fej mice. in both mouse strains an antierythrocyte autoantibody production that depended on the presence of functional cd4+ t lymphocytes was observed. ...	2005	16339752
viral persistence: parameters, mechanisms and future predictions.	for a virus to persist, it must actively curtail the host's antiviral immune response. here, we review the conceptual basis by which this can occur and discuss the subsequent fate of differentiated cells infected over long periods of time. we also consider how the compromised antiviral immune response can be revigorated or replaced with a potent response that purges the virus and thereby terminates persistent infection.	2006	16364742
ly9 (cd229)-deficient mice exhibit t cell defects yet do not share several phenotypic characteristics associated with slam- and sap-deficient mice.	signaling lymphocyte activation molecule (slam) family receptors are critically involved in modulating innate and adaptive immune responses. several slam family receptors have been shown to interact with the adaptor molecule sap; however, subsequent intracellular signaling is poorly defined. notably, mutations in slam-associated protein (sap) lead to x-linked lymphoproliferative disease, a rare but fatal immunodeficiency. although the slam family member ly9 (cd229) is known to interact with sap, ...	2006	16365421
hantavirus and arenavirus antibody prevalence in rodents and humans in trentino, northern italy.	the spatial and temporal distribution of hantavirus and arenavirus antibody-positive wild rodents in trentino, italy, was studied using immunofluorescence assays (ifa) in two long-term sites trapped in 2000-2003, and six other sites trapped in 2002. the overall hantavirus seroprevalence in the bank voles, clethrionomys glareolus (n=229) screened for puumala virus (puuv) antibodies was 0.4%, and that for apodemus flavicollis mice (n=1416) screened for dobrava virus (dobv) antibodies was 0.2%. ant ...	2006	16371172
novel antiviral strategies to combat human arenavirus infections.	arenaviruses merit significant attention both as tractable model systems to study acute and persistent viral infections, and as clinically important human pathogens. evidence indicates that lcmv remains present in the usa and europe and capable of causing significant morbidity in infected individuals, likely being a neglected human pathogen. moreover, new arenaviruses are being discovered in the americas on the average of one every three years, with some of them causing severe hemorrhagic fever. ...	2005	16375709
evaluating antigen-specific cytotoxic t lymphocyte responses by a novel mouse granzyme b elispot assay.	we have established novel elisa- and elispot-based assays specific for the detection of a potent cytotoxic mediator, granzyme b (grb), for the assessment of antigen-specific cytotoxic t lymphocyte responses in mice. the sensitivity and specificity of our assays was demonstrated by elisa using purified mouse grb and supernatants and cell lysates of cytotoxic lymphocytes derived from grb-deficient mice. no reactivity was observed by the grb elisa in grb-deficient cells. the mouse grb elispot was s ...	2006	16375915
structural basis of the differential stability and receptor specificity of h-2db in complex with murine versus human beta2-microglobulin.	beta(2)-microglobulin (beta(2)m) is non-covalently linked to the major histocompatibility complex (mhc) class i heavy chain and interacts with cd8 and ly49 receptors. murine mhc class i heavy chains can bind human beta(2)m (hbeta(2)m) and peptide, and such hybrid molecules are often used in structural and functional studies. the replacement of mouse beta(2)m (mbeta(2)m) with hbeta(2)m has several functional consequences for mhc class i complex stability and specificity, but the structural basis ...	2006	16375919
ube1l and protein isgylation are not essential for alpha/beta interferon signaling.	the expression of ubiquitin-like modifier isg15 and its conjugation to target proteins are highly induced by interferon (ifn) stimulation and during viral and bacterial infections. however, the biological significance of this modification has not been clearly understood. to investigate the function of protein modification by isg15, we generated a mouse model deficient in ube1l, an isg15-activating enzyme. ube1l-/- mice did not produce isg15 conjugates but expressed free isg15 normally. isgylatio ...	2006	16382139
restoring function in exhausted cd8 t cells during chronic viral infection.	functional impairment 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. to address this question, we analysed genes expressed in functionally impaired virus-specific cd8 t cells present in mice chronically infected with lymphocytic choriomeningitis virus (lcmv), and compared these with the gene profile of functional memory cd8 t cells. here we report that pd-1 (programmed death 1; also ...	2006	16382236
solid tumors "melt" from the inside after successful cd8 t cell attack.	adoptive transfer of tumor-specific t cells represents a promising approach for cancer immunotherapy. here, we visualized the anti-tumor response of cd8 t cells from p14 tcr-transgenic mice specific for the model antigen gp33 by immunohistology. p14 t cells, adoptively transferred into tumor-bearing hosts, induced regression of established 3ll-a9(gp33) and mca102(gp33) tumors that express gp33 as a tumor-associated model antigen. strikingly, the visible effects of p14 t cell attack, such as the ...	2006	16385625
interleukin-21 mrna expression during virus infections.	interleukin-21 is a cytokine with profound impact on the proliferation and differentiation of activated leukocytes of both the innate and adaptive immune system. in experiments in vitro, antigen activation induces il-21 production in cd4+ t cells. where, when, and how the proliferative and activational effects of il-21 on different leukocytes come into play in vivo in an immune response has so far not been fully investigated. we show here for the first time in vivo, that il-21 mrna is produced i ...	2006	16406655
perforin-deficient cd8+ t cells mediate fatal lymphocytic choriomeningitis despite impaired cytokine production.	intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (lcmv) is one of the most studied models for virus-induced immunopathology, and based on results from perforin-deficient mice, it is currently assumed that fatal disease directly reflects perforin-mediated cell lysis. however, recent studies have revealed additional functional defects within the effector t cells of lcmv-infected perforin-deficient mice, raising the possibility that perforin may not be directly involved in med ...	2006	16414999
tlr agonists abrogate costimulation blockade-induced prolongation of skin allografts.	costimulation blockade protocols are effective in prolonging allograft survival in animal models and are entering clinical trials, but how environmental perturbants affect graft survival remains largely unstudied. we used a costimulation blockade protocol consisting of a donor-specific transfusion and anti-cd154 mab to address this question. we observed that lymphocytic choriomeningitis virus infection at the time of donor-specific transfusion and anti-cd154 mab shortens allograft survival. lymp ...	2006	16424185
tec kinases itk and rlk are required for cd8+ t cell responses to virus infection independent of their role in cd4+ t cell help.	itk and rlk are members of the tec kinase family of nonreceptor protein tyrosine kinases that are expressed in t cells, nk cells, and mast cells. these proteins are involved in the regulation of signaling processes downstream of the tcr in cd4(+) t cells, particularly in the phosphorylation of phospholipase c-gamma1 after tcr activation; furthermore, both itk and rlk are important in cd4(+) t cell development, differentiation, function, and homeostasis. however, few studies have addressed the ro ...	2006	16424186
peptide vaccination of mice immune to lcmv or vaccinia virus causes serious cd8 t cell-mediated, tnf-dependent immunopathology.	cd8 t cells play a key role in clearing primary virus infections and in protecting against subsequent challenge. the potent antiviral effects of these cells make them important components of vaccine-induced immunity and, because of this, peptide vaccines often contain epitopes designed to induce strong cd8 t cell responses. however, the same effector functions that protect the host also can be harmful if they are not tightly regulated, and virus-specific cd8 t cells are a frequent cause of immun ...	2006	16424939
multiple sclerosis and virus induced immune responses: autoimmunity can be primed by molecular mimicry and augmented by bystander activation.	polymicrobial infections have been associated with plausible immune mediated diseases, including multiple sclerosis (ms). virus infection can prime autoimmune t cells specific for central nervous system (cns) antigens, if virus has molecular mimicry with cns proteins. on the other hand, infection of irrelevant viruses will induce two types of cytokine responses. infection with a virus such as lymphocytic choriomeningitis virus (lcmv), can induce interferon (ifn)-alpha/beta production and suppres ...	2006	16455578
rescue of the prototypic arenavirus lcmv entirely from plasmid.	we document a helper-independent reverse genetics system for rescuing infectious arenaviruses from cloned cdnas. we constructed plasmids containing full-length cdnas of the antigenomic (ag) l and s segments of the armstrong (arm) strain of the prototypic arenavirus lymphocytic choriomeningitis virus (lcmv) flanked at their 5'- and 3'-termini by the t7 rna polymerase (t7rp) promoter and ribozyme sequences, respectively. these plasmids directed intracellular synthesis of viral l and s ag rna speci ...	2006	16476461
role of non-raft cholesterol in lymphocytic choriomeningitis virus infection via alpha-dystroglycan.	dystroglycan (dg) is an extracellular matrix receptor necessary for the development of metazoans from flies to humans and is also an entry route for various pathogens. lymphocytic choriomeningitis virus (lcmv), a member of the family arenaviridae, infects by binding to alpha-dg. here, the role of cholesterol lipid rafts in infection by lcmv via alpha-dg was investigated. the cholesterol-sequestering drugs methyl-beta-cyclodextrin (mbetacd), filipin and nystatin inhibited the infectivity of lcmv ...	2006	16476990
precursor frequency, nonlinear proliferation, and functional maturation of virus-specific cd4+ t cells.	the early events regulating antiviral cd4 responses were tracked using an adoptive transfer model. cd4+ t cell expansion was nonlinear, with a lengthy lag phase followed by 2 days of explosive proliferation. a small number of naive ag-specific cd4+ t cells were found in nonlymphoid tissues and, in the 8 days following infection, the number of activated cells increased in all tissues analyzed, and their effector functions matured. finally, we show that a naive mouse contains approximately 100 nai ...	2006	16493061
phylogeny and evolution of old world arenaviruses.	the intention of this study was to investigate the genomics, phylogeny and evolution of the old world arenaviruses based on sequence data representing the four viral genes. to achieve this aim, we sequenced the complete s and l rna segments of ippy virus (ippyv), mobala virus (mobv) and mopeia virus (mopv). full-length sequences of the np, gpc, z and l genes were used to reconstruct phylogenetic relationships and to compare resulting tree topologies. each of the five old world arenavirus species ...	2006	16494913
antiviral antibody responses: the two extremes of a wide spectrum.	viruses elicit a diverse spectrum of antiviral antibody responses. in this review, we discuss two widely used experimental model systems for viral infections - non-cytopathic lymphocytic choriomeningitis virus (lcmv) and acutely cytopathic vesicular stomatitis virus (vsv) - to analyse two fundamentally different types of antiviral antibody response. the basic principles found in these model infections are discussed in the context of other viral infections, and with regard to protective neutraliz ...	2006	16498452
expression, refolding and crystallization of murine mhc class i h-2db in complex with human beta2-microglobulin.	beta2-microglobulin (beta2m) is non-covalently linked to the major histocompatibility (mhc) class i heavy chain and interacts with cd8 and ly49 receptors. murine mhc class i can bind human beta2m (hbeta2m) and such hybrid molecules are often used in structural and functional studies. the replacement of mouse beta2m (mbeta2m) by hbeta2m has important functional consequences for mhc class i complex stability and specificity, but the structural basis for this is unknown. to investigate the impact o ...	2005	16511243
cutting edge: the direct action of type i ifn on cd4 t cells is critical for sustaining clonal expansion in response to a viral but not a bacterial infection.	the action of type i ifn (ifn-i) on apcs is well studied, but their direct effect on cd4 t cells is unclear. to address this, we transferred ifn-i receptor-deficient (ifn-ir(0)) and -sufficient (wild-type, wt) tcr-transgenic cd4 t cells into wt mice and analyzed their response to immunization. in response to lymphocytic choriomeningitis virus immunization, wt cd4 t cells expanded approximately 100-fold, whereas ifn-ir(0) cd4 t cells expanded <10-fold. however, both wt and ifn-ir(0) cd4 t cells e ...	2006	16517698
soluble mhc-peptide complexes containing long rigid linkers abolish ctl-mediated cytotoxicity.	soluble mhc-peptide (pmhc) complexes induce intracellular calcium mobilization, diverse phosphorylation events, and death of cd8+ ctl, given that they are at least dimeric and co-engage cd8. by testing dimeric, tetrameric, and octameric pmhc complexes containing spacers of different lengths, we show that their ability to activate ctl decreases as the distance between their subunit mhc complexes increases. remarkably, pmhc complexes containing long rigid polyproline spacers (> or =80 a) inhibit t ...	2006	16517703
taking the brake off t cells in chronic viral infection.		2006	16520769
cd69 acts downstream of interferon-alpha/beta to inhibit s1p1 and lymphocyte egress from lymphoid organs.	naive lymphocytes continually enter and exit lymphoid organs in a recirculation process that is essential for immune surveillance. during immune responses, the egress process can be shut down transiently. when this occurs locally it increases lymphocyte numbers in the responding lymphoid organ; when it occurs systemically it can lead to immunosuppression as a result of the depletion of recirculating lymphocytes. several mediators of the innate immune system are known to cause shutdown, including ...	2006	16525420
aicardi-like chorioretinitis and maldevelopment of the corpus callosum in congenital lymphocytic choriomeningitis virus.		2006	16527682
recovery of an arenavirus entirely from rna polymerase i/ii-driven cdna.	the prototypic arenavirus lymphocytic choriomeningitis virus has been a primary workhorse of viral immunologists for almost a century, and it has served as an important model for studying basic principles of arenavirus molecular biology. its negative-stranded bisegmented rna genome has, however, posed a major obstacle to attempts at manipulating the infectious virus by reverse genetic techniques. here, we report the recovery of infectious lymphocytic choriomeningitis virus (the immunosuppressive ...	2006	16537369
cxcl10 is the key ligand for cxcr3 on cd8+ effector t cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system.	ifn-gamma-inducible protein 10/cxcl10 is a chemokine associated with type 1 t cell responses, regulating the migration of activated t cells through binding to the cxcr3 receptor. expression of both cxcl10 and cxcr3 are observed during immunopathological diseases of the cns, and this receptor/ligand pair is thought to play a central role in regulating t cell-mediated inflammation in this organ site. in this report, we investigated the role of cxcl10 in regulating cd8(+) t cell-mediated inflammati ...	2006	16547260
ifn-induced attrition of cd8 t cells in the presence or absence of cognate antigen during the early stages of viral infections.	profound lymphopenia has been observed during many acute viral infections, and our laboratory has previously documented a type i ifn-dependent loss of cd8 t cells immediately preceding the development of the antiviral t cell response. most memory (cd44(high)) and some naive (cd44(low)) cd8 t cells are susceptible to ifn-induced attrition, and we show in this study that the ifn-induced attrition of cd8(+)cd44(high) t cells is associated with elevated activation of caspase-3 and caspase-8. we ques ...	2006	16547266
long-lived memory cd8+ t cells are programmed by prolonged antigen exposure and low levels of cellular activation.	cd8+ t cells play a crucial role in controlling intracellular pathogens. the level of memory cd8+ t cells developing after vaccination or infection influences the degree of t cell-mediated protection after secondary infection. we used defined animal models and infections/immunizations by replicating or non-replicating antigens to define on a molecular and cellular level in vivo the parameters that identify and shape long-lived cd8+ t cell memory. we show that the timing of antigen exposure durin ...	2006	16552716
is there an association of pneumocystis infection with the presence of arena-, hanta-, and poxvirus antibodies in wild mice and shrews in finland?	as part of studies on the nature of the endemic virus infections in natural rodent hosts, the possible association of cyst forms of pneumocystis spp. with the presence of hanta-, cowpox-, and arenavirus antibodies in wild mice (apodemus flavicollis, n=105; apodemus agrarius, n=63; micromys minutus, n=50) and the common shrew (sorex araneus, n=101) was studied in south-central finland. one hantavirus (saaremaa virus, saav) seropositive a. agrarius, and 2 cowpoxvirus (cpxv) seropositive s. araneus ...	2006	16556344
responses of the peyer's patches in germ-free mice to antigenic stimulation.	lymph nodes, spleens, and peyer's patches of germ-free mice are relatively inactive. the tissues are small and contain rare, small, indistinct, germinal zones. when exposed to antigenic stimuli (salmonella paratyphi a and lymphocytic choriomeningitis virus), the tissues become larger and germinal zones appear coincident with antibodies in the blood. the peyer's patches were activated if antigen was absorbed from the intestinal lumen into the circulation but not if the antigen was administered pa ...	1970	16557807
persistent infection of mice with the virus of lymphocytic choriomeningitis: virus-specific immunological tolerance.	lymphocytic choriomeningitis (lcm) virus-infected culture cells as targets were markedly reduced in numbers when incubated in vitro with spleen cells from lcm virus-immune mice, even if the cells were taken months after a subcutaneous immunizing infection of the donor animal. spleen cells from mice persistently infected with lcm virus had no effect on target cells. also, mitomycin c-blocked lcm virus-infected culture cells stimulated the incorporation of radiolabeled thymidine into spleen cells ...	1974	16558092
augmenting the immunogenicity of dna vaccines: role of plasmid-encoded flt-3 ligand, as a molecular adjuvant in genetic vaccination.	in this study, we have taken advantage of the unique property of a potent dendritic cell (dc) growth factor, flt-3 ligand (fl), which could act as a vaccine adjuvant. accordingly, a single injection of plasmid dna coding for soluble fl (flex) was shown to induce large numbers of dcs in various tissue compartments and was critical for generating high frequencies of antigen-specific (hiv gp120 and lcmv np) immune responses in mice. interestingly, this enhanced level of immune response is strictly ...	2006	16563456
adventitious agent test methods.		2006	16566441
arenavirus diversity and evolution: quasispecies in vivo.	arenaviruses exist as viral quasispecies due to the high mutation rates of the low-fidelity viral rna-dependent rna polymerase (rdrp). this genomic heterogeneity is advantageous to the population, allowing for adaptation to rapidly changing environments that present varying types and degrees of selective pressure. the significant variation in biological properties observed among lymphocytic choriomeningitis virus (lcmv) strains, the prototypic arenavirus, indicates to what extent a quasis-pecies ...	2006	16568904
cdc on the offensive to stamp out rodent virus.		2006	16579771
cd8 t cells specific for lymphocytic choriomeningitis virus require type i ifn receptor for clonal expansion.	the role of type i ifn signaling in cd8 t cells was analyzed in an adoptive transfer model using p14 tcr transgenic cd8 t cells specific for lymphocytic choriomeningitis virus (lcmv) but deficient in type i ifnr. in the present study, we demonstrate severe impairment in the capacity of p14 t cells lacking type i ifnr to expand in normal type i ifnr wild-type c57bl/6 hosts after lcmv infection. in contrast, following infection of recipient mice with recombinant vaccinia virus expressing lcmv glyc ...	2006	16585541
dna methylation by dna methyltransferase 1 is critical for effector cd8 t cell expansion.	transcriptional silencing mediated by dna methylation is a critical component of epigenetic regulation during early embryonic development in animals. however, the requirement for dna methylation during activation and differentiation of mature cd8+ t cells into effector and memory cells is not clear. using cre-mediated deletion of dna methyltransferase 1 (dnmt1) at the time of cd8+ t cell activation, we investigated the obligation for maintaining patterns of dna methylation during the generation ...	2006	16585546