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severe and transient pancytopenia associated with a chronic arenavirus infection.a so-called 'docile' strain of lymphocytic choriomeningitis virus (lcmv) lacks the ability to cause the fatal central nervous system syndrome, commonly associated with most other strains of this virus, in c3heb/fej mice. hematological evaluation during a 5 week period revealed that every mouse experienced a pancytopenia which was the most severe around three weeks post-infection. the abnormal red blood cell (rbc) morphology seen in the peripheral blood along with the increased reticulocyte count ...19872835466
inhibition of hsv-1 and vaccinia virus replication by cephalosporin derivatives.derivatives of beta-lactam antibiotics of the cephalosporin type at 0.02-1 mm concentrations interfered with in vitro replication of two dna-containing viruses, herpes simplex i and vaccinia, but showed no effects on two rna-viruses, lymphocytic choriomeningitis virus and vesicular stomatitis virus, or on cell viability. the exact structure of the active compounds remains unknown, but opening of the beta-lactam ring appears to be a prerequisite for their formation. whereas cephalosporin derivati ...19882852920
the immune response of the mouse to lymphocytic choriomeningitis virus. v. high numbers of cytolytic t lymphocytes are generated in the spleen during acute infection.in the spleens of c57bl/6j (b6) and cba/j (cba) mice undergoing acute infection with lymphocytic choriomeningitis (lcm) virus, lymphocytes with the ability to develop in vitro into lcm virus-specific cytolytic clones were enumerated by use of the limiting dilution method. at intervals after virus inoculation, defined numbers of cells were cultivated with virus-infected syngeneic stimulator cells and t cell growth factor in multiple wells of microculture plates. after 7 days, individual cell cult ...19872886344
anti-lcmv immune serum preparation and its testing by complement fixation test and immunoelectroosmophoresis. 19882899967
viral infection of neurons can depress neurotransmitter mrna levels without histologic injury.neonatal mice inoculated with lymphocytic choriomeningitis virus (lcmv) have non-lytic persistent neuronal infection and disturbed behavior. we now show that lcmv replicates in neurons containing the neurotransmitter somatostatin without morphologic evidence of injury and that persistent neuronal lcmv infection in mice is attended by a decrease in brain levels of somatostatin mrna. brain levels of mrna for another neurotransmitter peptide, cholecystokinin, are not decreased. these data are the f ...19882908027
lymphocytic choriomeningitis virus selectively alters differentiated but not housekeeping functions: block in expression of growth hormone gene is at the level of transcriptional initiation.persistent infection with lymphocytic choriomeningitis virus (lcmv) armstrong strain in c3h/st mice is associated with a growth hormone (gh) deficiency syndrome, characterized by growth retardation and low serum glucose levels (m.b.a. oldstone et al., 1982, science 218, 1125-1127). the syndrome is associated with a decrease in gh synthesis in the pituitary gland, in the absence of cellular injury in the pituitary or associated brain areas. in this report, we demonstrate that the decreases in ste ...19892916325
nucleotide sequence of the lassa virus (josiah strain) s genome rna and amino acid sequence comparison of the n and gpc proteins to other arenaviruses.the complete nucleotide sequence of the s genome rna of the josiah strain of lassa virus was determined from cloned cdna. the s rna is 3402 nucleotides long with a calculated molecular weight of 1.09 x 10(6) da. the nucleotide base composition is 26.84% adenine, 21.40% guanine, 22.75% cytosine, and 29.01% uridine. the 5' and 3' terminal nucleotide sequences are conserved and complimentary for 19 nucleotides, the nucleoprotein and glycoprotein genes are arranged in ambisense coding strategy, and ...19892916333
homologous interference of lymphocytic choriomeningitis virus involves a ribavirin-susceptible block in virus replication.depending on the multiplicity of infection (moi), infection of l929 cells results in either productive lymphocytic choriomeningitis virus replication or homologous interference m. bruns, a. gessner, h. lother, and f. lehmann-grube, virology 166:133-139, 1988). as shown in this communication, productive lymphocytic choriomeningitis virus replication as observed at a low moi was effectively inhibited by ribavirin. in contrast, virus yields increased if cells were infected with a high moi and in th ...19892926867
persistent virus infection associated with chemical manifestations of diabetes. ii. role of viral strain, environmental insult, and host genetics.abnormal glucose metabolism (hyperglycemia and/or aberrant glucose tolerance test) occurred over the life-times of mice persistently infected with lymphocytic choriomeningitis virus (lcmv). persistent infection could be initiated in both newborn and adult mice. for newborns, inoculation with any of several strains of lcmv (armstrong, e350, pasteur, traub or we) caused continuous infection, but such infection of adults required a selected lymphotropic variant of lcmv armstrong (clone 13). through ...19872949622
virus-lymphocyte interaction: t cells of the helper subset are infected with lymphocytic choriomeningitis virus during persistent infection in vivo.the lifelong persistence of lymphocytic choriomeningitis virus (lcmv) in neonatally or congenitally infected mice is accompanied by a suppression of virus-specific t-cell responses. in this study, we identified the subset of t cells infected with lcmv during persistent infection in vivo. using specific monoclonal antibodies to separate the different lymphocyte cell populations and employing both an infectious center assay and immunofluorescence to detect the virus, we found that infection is con ...19872952807
molecular analysis of the antigen receptor of virus-specific cytotoxic t cells and identification of a new v alpha family.we have determined the primary structure of the alpha/beta-antigen receptor of a lymphocytic choriomeningitis virus (lcmv)-specific cytotoxic t cell clone (p14). the beta chain of the t cell receptor is composed of v beta 8.1, d beta and j beta 2.4 gene segments while the alpha chain uses a member of the v alpha 2 family and j alpha ta31. southern blot analysis of a panel of six other independent lcmv-specific cytotoxic t cell clones did not reveal any preferential usage of the v alpha 2 or v be ...19872961577
virus-lymphocyte interactions. ii. expression of viral sequences during the course of persistent lymphocytic choriomeningitis virus infection and their localization to the l3t4 lymphocyte subset.viruses that cause in vivo persistent infections need to selectively compromise the host's immunologic surveillance machinery in order to survive. to understand the molecular basis of how this is accomplished we have analyzed persistent virus infection by lymphocytic choriomeningitis in its normal host, the mouse. earlier we noted by infectious center analysis that five in 10(4) lymphocytes carried by persistently infected mice contained infectious materials throughout the course of infection. a ...19882963865
virus-triggered immune suppression in mice caused by virus-specific cytotoxic t cells.normal mice infected with 10(5) infectious doses of lymphocytic choriomeningitis virus (lcmv, we isolate) generated a reduced or no t cell-independent igm and/or t cell-dependent igg response to a subsequent vesicular stomatitis virus indiana (vsv-ind) injection; this transient immune suppression lasted for weeks to months. connatally infected lcmv-carrier mice or acutely infected t cell-deficient nude mice had normal anti-vsv igm and igg or igm responses respectively. lcmv-infected nude mice tr ...19882966846
t4+ t helper cell function in vivo: differential requirement for induction of antiviral cytotoxic t-cell and antibody responses.this study documents the differential requirements of t4+ t helper cells in the induction of virus-specific cytotoxic t-lymphocyte (ctl) and antibody responses during acute lymphocytic choriomeningitis virus infection. two monoclonal antibodies (gk1.5 and rl172.4) directed against the l3t4 (t4) molecule were used for depleting t helper cells from mice. depletion of t4+ cells caused a pronounced suppression of antiviral antibody response (20-fold decrease) but had minimal effect on virus-specific ...19882966865
virus-lymphocyte interactions. iii. biologic parameters of a virus variant that fails to generate ctl and establishes persistent infection in immunocompetent hosts.viruses that cause in vivo persistent infections avoid the host's immunologic surveillance machinery. a major component of that armamentarium is virus-specific mhc-restricted cytotoxic t lymphocyte (ctl) response of the host. studies with lymphocytic choriomeningitis virus (lcmv) have uncovered a parental virus (ctl+) that in immuno-competent adults induces ctl and terminates acute infection and a variant (ctl-) that fails to elicit ctl responses and establishes a persistent state (r. ahmed et a ...19882967012
thymic selection of h-2-incompatible bone marrow cells in scid mice. differences in t help for induction of b cell igg responses versus cytotoxic t cells.mice with congenital severe combined immunodeficiency disease (scid) failed to mount either a t cell-independent igm or t cell-dependent igg anti-vesicular stomatitis virus (vsv) indiana (ind) response. they did not generate cytotoxic t cells against lymphocytic choriomeningitis virus (lcmv) or vaccinia virus, but exhibited nk cell-like activities. when scid mice were given bone marrow from syngeneic balb/c (h-2d) nu/nu mice, all immune responses were expressed at control levels. if scid mice we ...19882971754
virtue in viruses. 19882972062
contributions of host and donor t cells to the inflammatory process in murine lymphocytic choriomeningitis.the severe inflammation characteristic of the infection of adult mice with murine lymphocytic choriomeningitis virus (lcmv) is induced earlier in unsuppressed, virus-infected recipients by the adoptive transfer of class i mhc-compatible, cd4- cd8+ lcmv-immune spleen cell populations. the time to onset of fatal lcm may also be slightly diminished, though not to the extent that would be expected from the enhanced kinetics of the extravasation of cells into cerebrospinal fluid. the development of s ...19882972391
natural killer cells vs cytotoxic t cells in the peripheral blood of virus-infected mice.the cell-mediated immune response of mice against various enveloped rna and dna viruses expressed by immune lymphocytes from the spleen and the peripheral blood (pbl) were compared. pbl from mice of various strains infected with vaccinia virus, vesicular stomatitis virus (vsv), or lymphocytic choriomeningitis virus (lcmv) were tested on histocompatible or incompatible target cells infected with the homologous virus. pbl from immune mice showed clear h-2 restriction, but additionally, they expres ...19852981094
suppression by cyclosporin a of murine t-cell-mediated immunity against viruses in vivo and in vitro.the immunosuppressive effect of cyclosporin a on t-cell-mediated antiviral immune responses was examined. when administered intraperitoneally cs-a abrogated anti-vaccinia virus, anti-lymphocytic choriomeningitis virus (lcmv), and anti-vesicular stomatitis virus (vsv) t-cell responses in a dose-dependent fashion. usually 50-60 mg/kg were efficient in suppressing primary t-cell responses completely. in contrast, 10-20 mg/kg often enhanced t-cell responses significantly when compared with controls. ...19852981641
adoptive transfer studies demonstrating the antiviral effect of natural killer cells in vivo.we carried out adoptive transfer studies to determine the role of natural killer (nk) cells in resistance to murine cytomegalovirus (mcmv) and lymphocytic choriomeningitis virus (lcmv). we transferred leukocytes from adult mice into suckling mice 1 d before injecting them with virus. resistance was measured by enhancement of survival and reduction of virus multiplication in the spleens of recipient mice. the phenotype of the cell population capable of mediating resistance to mcmv was that of a n ...19852981954
abrogation of anti-pichinde virus cytotoxic t cell memory by cyclophosphamide and restoration by coinfection or interleukin 2.previously, we demonstrated that memory cell-mediated immune responses can be generated in pichinde virus (pv)-primed mice after secondary challenge in vivo with homologous virus. further, treatment of mice with cyclophosphamide (cy) before primary infection with pv abrogated the generation of h-2-restricted, virus-specific cytotoxic t lymphocytes (ctl), and rechallenge of these mice was followed by neither a primary nor a secondary ctl response. here, we demonstrate that this cy-induced block i ...19852989365
studies on the mechanism of lymphocytic choriomeningitis virus homologous interference. 19863014286
accumulation and chemotaxis of natural killer/large granular lymphocytes at sites of virus replication.a model for monitoring the accumulation of natural killer cell/large granular lymphocytes (nk/lgl) at a site of virus replication was studied by using mice infected i.p. with either lymphocytic choriomeningitis virus (lcmv), murine cytomegalovirus (mcmv), mouse hepatitis virus (mhv), pichinde virus, or vaccinia virus. an i.p. but not i.v. infection resulted in a localized increase in nk/lgl cell number (a fourfold to greater than 20-fold increase) and augmentation (a 10- to 20-fold increase) of ...19873027167
viruses perturb lymphocyte functions: selected principles characterizing virus-induced immunosuppression. 19873036182
recovery from acute virus infection. role of cytotoxic t lymphocytes in the elimination of lymphocytic choriomeningitis virus from spleens of mice. 19883052209
immunopathological reactions in viral infections of the central nervous system.viral infections of the central nervous system (cns), as of any other organ, evoke humoral and cellular immune responses which enable the host to eliminate the pathogen. however, effective responses may themselves produce tissue damage sometimes exceeding that caused by the virus itself. the relative contribution of the various immunopathological mechanisms in human viral encephalitides remains mostly ill defined. most of our understanding of the immunopathogenesis in viral cns infections comes ...19883058742
induction or prevention of immunopathological disease by cloned cytotoxic t cell lines specific for lymphocytic choriomeningitis virus.cloned lymphocytic choriomeningitis virus (lcmv)-specific cytotoxic t lymphocyte (ctl) lines were prepared from spleens of 129/j (h-2b) mice immunized 7-9 months earlier with lcmv (ubc strain), or of c57bl/10j (h-2b) mice immunized 4 to 5 weeks earlier with lcmv (armstrong strain). one uncloned and 3 cloned cytotoxic t cell lines were assessed for their respective abilities to produce, or protect against, fatal disease upon transfer to appropriate recipients or to induce specific footpad-swellin ...19863084281
cytoimmunotherapy for persistent virus infection reveals a unique clearance pattern from the central nervous system.the mechanism(s) by which infectious or malignant material is cleared by the host has long been an area of intensive study. we have used the murine model of infection with lymphocytic choriomeningitis virus (lcmv) to look at immune clearance during persistent infection. lcmv was selected because the mouse is its natural host, it easily induces acute or persistent infection in vivo, and the mechanism by which it is cleared in vivo during acute infection is now well understood. clearance, although ...19863086743
distortion of cell functions by noncytotoxic viruses. 19863088015
questionable role of mononuclear phagocytes in the elimination of lymphocytic choriomeningitis virus from spleens of acutely infected mice. 19863088409
a specific serine proteinase is inducible in lyt-2+,l3t4- and lyt-2-,l3t4+ t cells in vitro but is mainly associated with lyt-2+,l3t4- effector cells in vivo.recently, we and others reported on the expression of a serine proteinase in long-term cultured murine t lymphocyte cell lines. in an attempt to explore the distribution and possible regulation of this enzyme in t lymphocyte subsets, we performed the presented detailed study. we found that the proteinase is not expressed by thymocytes and resting t cells but can be induced by lectin or antigen in combination with lymphokine sources in vitro in macrophage-depleted unselected t cells as well as in ...19863102247
expression of pgp-1 (or ly24) by subpopulations of mouse thymocytes and activated peripheral t lymphocytes.the expression of pgp-1 (ly24) by subpopulations of thymocytes was investigated and a subpopulation of lyt-2-/l3t4-/j11d- thymocytes was identified which contained significant numbers (80%) of pgp-1+ cells. among freshly isolated lymph node t cells but not cortisone-resistant thymocytes, pgp-1 expression was heterogeneous. stimulation of t lymphocytes with either concanavalin a or the combination of phorbol myristate acetate plus calcium ionophore resulted in increased pgp-1 expression which was ...19873102251
nature of the inflammatory process in the central nervous system of mice infected with lymphocytic choriomeningitis virus. 19873107910
phenotypic analysis of the inflammatory exudate in murine lymphocytic choriomeningitis.the massive inflammation of the cerebrospinal fluid (csf) which occurs in adult mice injected with lymphocytic choriomeningitis virus (lcmv) has been analyzed by flow microfluorometry (fmf). the great majority of the t cells detected by direct examination of freshly obtained csf were found to be lyt-2+, with an almost total absence of l3t4+ lymphocytes. the lyt-2/l3t4 ratio of lymphocytes in blood was within normal limits. predominance of the lyt-2+ subset was confirmed by culturing the csf cell ...19873108445
production of b cell stimulatory factor-2 and interferon gamma in the central nervous system during viral meningitis and encephalitis. evaluation in a murine model infection and in patients.synthesis of b cell-stimulating factor-2 (bsf-2) and ifn-gamma was shown in cerebrospinal fluids (csf) collected from mice with experimental viral meningitis. in the csf, the level of bsf-2 started to increase 24 h after intracerebral infection with lymphocytic choriomeningitis virus (lcmv) with rapid increase after day 4. ifn-gamma was not detected in the csf before day 5 or 6 after infection, but increased sharply thereafter. in athymic nude mice, lcmv infection did not result in meningitis, a ...19883135367
increased bactericidal macrophage activity induced by immunological stimuli is dependent on interferon (ifn)-gamma. interference of anti-ifn-gamma but not anti-ifn-alpha/beta with modulation of macrophage activity caused by lymphocytic choriomeningitis virus infection or systemic graft-vs.-host reactions.during generalized immune responses such as the acute phase of graft-vs.-host reaction (gvhr) or many systemic viral infections the macrophage-monocyte system of mice is activated as demonstrated by their increased bactericidal capacity against listeria monocytogenes. to study the effect of interferon (ifn)-gamma in maintainance of macrophage activity, lymphocytic choriomeningitis virus (lcmv) primed c57bl/6 mice or (c57bl/10 x b10.br) f1 mice undergoing a gvhr were treated with polyclonal speci ...19883138138
the incidence of diabetes in bb rats is decreased following acute lcmv infection. 19883250261
analyses of the cytotoxic t lymphocyte responses to glycoprotein and nucleoprotein components of lymphocytic choriomeningitis virus.the outcome of infection by lymphocytic choriomeningitis virus (lcmv) in the natural murine host is determined in large part by the cytotoxic t lymphocyte response (ctl) mounted by the host. in order to define the specificities of ctl induced by lcmv infection, we have cloned and expressed the full-length nucleoprotein (np) gene and 75% of the glycoprotein (gp) gene of lcmv in vaccinia virus vectors and have used these recombinant viruses to sensitize syngeneic target cells to lysis by anti-lcmv ...19883257596
immunogenetic analysis of cellular interactions governing the recruitment of t lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology.the lyt2+ class i major histocompatibility complex (mhc)-restricted virus-immune t cells that induce murine lymphocytic choriomeningitis (lcm) are targeted onto radiation-resistant cells in the central nervous system of virus-infected mice. the use of appropriate bone marrow radiation chimeras as lcm virus-infected, (immunosuppressed recipients for immune t-cell transfer has established that, though bone marrow-derived cells can stimulate virus-specific cytotoxic t lymphocytes (ctl) in spleen, t ...19883258209
t-cell tolerance: exposure to virus in utero does not cause a permanent deletion of specific t cells.this study documents the curing of a congenitally acquired chronic viral infection and the acquisition of t-cell competence by a previously tolerant host. infection of mice with lymphocytic choriomeningitis virus (lcmv) is a classic model of viral persistence and antigen-specific t-cell unresponsiveness. mice infected at birth or in utero become lifelong carriers with no detectable virus-specific cytotoxic t lymphocyte (ctl) responses. this chronic infection can be eliminated by adoptive transfe ...19883258424
clearance of lymphocytic choriomeningitis virus in antibody- and b-cell-deprived mice.the role of antibody in immune recovery from infection with lymphocytic choriomeningitis virus (lcmv) strain we was evaluated in b-cell-depleted mice. mice were treated from birth with either affinity-purified rabbit anti-mouse immunoglobulin m (igm), normal rabbit immunoglobulin, or, alternatively, an affinity-purified monoclonal rat anti-mouse igm antibody (lo-mm-9); untreated mice served as controls. b-cell depletion was considered complete in specifically treated mice according to the follow ...19883258641
virus-lymphocyte interactions. iv. molecular characterization of lcmv armstrong (ctl+) small genomic segment and that of its variant, clone 13 (ctl-).immunocompetent adult mice mount a vigorous cytotoxic t lymphocyte (ctl) response against the armstrong (arm) 53b strain of lcmv after primary inoculation. in contrast, the clone 13 variant of arm 53b, originally isolated from the spleen of a persistently infected mouse, suppresses lcmv-specific ctl responses (r. ahmed et al. (1984) j. exp med 60, 521). the induction and generation of ctl maps to the short (s) rna segment and not the long (l) rna segment of lcmv (y. riviere et al. (1986) j. immu ...19883259346
induction of t cell serine proteinase 1 (tsp-1)-specific mrna in mouse t lymphocytes.an oligonucleotide probe corresponding to nucleotides of a cdna encoding the t cell-associated proteinase 1 (tsp-1) was chosen to study the induction and expression of tsp-1-specific transcripts in mouse t lymphocytes and tissues. we demonstrate that tsp-1 mrna is only expressed in activated t lymphocytes and is absent from all mouse tissues tested including those containing resting mature t lymphocytes. expression of the tsp-1 gene was observed in t lymphocytes in vitro in response to either ph ...19883260181
mechanism of recovery from acute virus infection. vi. replication of lymphocytic choriomeningitis virus in and clearance from the foot of the mouse.the hind foot was chosen for study of the mechanism by which adult mice clear lymphocytic choriomeningitis (lcm) virus. the t cell-mediated swelling that follows the local inoculation of virus allows parallel investigation of the infectious process and delayed-type hypersensitivity in one organ. a dose of 10(5) mouse infectious units (iu) was optimal, and in all mouse strains tested foot swelling commenced 6 days after injection, with maximal response on days 7 and 8. when mice were sensitized b ...19883261324
genetic analysis of in vivo-selected viral variants causing chronic infection: importance of mutation in the l rna segment of lymphocytic choriomeningitis virus.viral variants with different biological properties are present in the central nervous systems (cns) and lymphoid tissues of mice persistently infected with lymphocytic choriomeningitis virus (lcmv). viral isolates from the cns are similar to the original armstrong lcmv strain and induce potent virus-specific t-cell responses in adult mice, and the infection is rapidly cleared. in contrast, lcmv isolates derived from spleens of carrier mice cause persistent infections in adult mice. this chronic ...19883261347
the complementary roles of cellular and humoral immunity in resistance to re-infection with lcm virus.the mechanisms underlying resistance to re-infection with lymphocytic choriomeningitis virus (lcmv) were investigated. rechallenge with moderate doses of virus (10(3) ld50) did not lead to detectable re-infection nor to re-induction of virus-specific cytotoxicity. when higher doses of virus were used for rechallenge (10(6) - 10(8) ld50), significant re-infection as well as reactivation of cytotoxicity were observed. both resistance and memory expression were controlled by an antigen-specific, ra ...19883263315
distinct patterns of virus-specific t cell-mediated cytolysis of transformed versus primary target cells.ideas about the mechanism(s) by which cytotoxic t lymphocytes (ctl) lyse appropriate target cells are still controversial. we studied the action of established murine ctl clones as well as of freshly prepared primarily induced ctl against two types of target cells. transformed tumour cell lines (mc57g and l929) and untransformed cells such as peritoneal exudate cells (pec) or fibroblasts were examined as target cells by scanning and transmission electron microscopy and with the 51cr-release assa ...19883264082
virus-specific memory t cells are pgp-1+ and can be selectively activated with phorbol ester and calcium ionophore.memory lymphocytic choriomeningitis virus (lcmv)-immune cytotoxic t-lymphocyte precursors (ctlp) can be stimulated to proliferate and to mediate specific cytotoxic activity following incubation with phorbol myristate acetate (pma), calcium ionophore (cai), and interleukin 2 (il-2). this protocol can be used to selectively induced virus-specific ctl activity under both bulk culture and limiting dilution conditions, in the absence of added antigen. there is no concurrent stimulation of alloreactiv ...19883282677
abrogation of diabetes in bb rats by acute virus infection. association of viral-lymphocyte interactions.the bb rat spontaneously develops an insulin-dependent diabetes mellitus (iddm) that closely resembles this disease in man. the pathogenesis involves autoimmune destruction of pancreatic beta-cells. in the present study, inoculation of diabetes-prone bb rats at 30 days of age with a lymphotropic variant of lymphocytic choriomeningitis virus significantly reduced the incidence of diabetes. such virus-inoculated, diabetes-free rats had normal levels of pancreatic insulin and little or no mononucle ...19883283232
molecular and genetic aspects of the pathogenesis of viral infections of the central nervous system.viral pathogenesis can be defined in terms of a series of successive interactions between a virus and its target host. in order for a virus to injure a target organ such as the central nervous system (cns), it must first enter the host animal, replicate in some primary site near its place of entry, spread from this site to the cns and infect and injure specific populations of cells within the cns. at each of these steps, the virus must avoid or overcome a variety of immunological and nonimmunolo ...19873315238
analysis of the genomic l rna segment from lymphocytic choriomeningitis virus.the arenavirus genomic l rna segment represents approximately 70% of the viral genetic material but current understanding of the organization, regulation, and functioning of the viral l products remains limited. biological studies with reassortant viruses have implicated the l rna segment in the lethal infection of adult guinea pigs produced by lcmv-we but no further explanation of the pathogenic process is presently available. we have initiated a detailed molecular analysis of lcmv l products b ...19873318094
the development of multiple expression vectors for high level synthesis of eukaryotic proteins: expression of lcmv-n and acnpv polyhedrin protein by a recombinant baculovirus.a copy of the polyhedrin gene promoter of autographa californica nuclear polyhedrosis virus (acnpv), in association with the coding region of lymphocytic choriomeningitis virus n protein (lcmv-n) and the relevant polyhedrin transcription termination signals, has been cloned into the unique ecorv site of a plasmid representing an ecori derived fragment of the acnpv genome. the cloning site is upstream (but in the opposite orientation) of the natural acnpv polyhedrin gene. the derived pacvc2 trans ...19873334094
temporal analysis of transcription and replication during acute infection with lymphocytic choriomeningitis virus.we have analyzed the accumulation of viral genomic and messenger rnas in tissue culture cells during the first 24 hr of acute infection with lymphocytic choriomeningitis virus (lcmv). this has allowed comparison of the relative amounts of the genomic l and s rnas (both genomic sense and genomic complementary sense) and of nucleoprotein (np) and glycoprotein precursor (gp-c) mrnas. using these techniques np mrna was detected simultaneously with genomic s rna, but the amount of np mrna accumulatin ...19883336942
lymphocytic choriomeningitis virus. x. demonstration of nucleoprotein on the surface of infected cells.of a total of 17 monoclonal antibodies (mab) directed against structural proteins of the lymphocytic choriomeningitis (lcm) virus, 3 were specific for the viral nucleoprotein (p63) and attached to the plasma membrane of infected cells, as disclosed by the indirect immunofluorescence procedure and complement-mediated cytolysis. we had previously demonstrated that a portion of the nucleoprotein (p63e) was part of the envelope of the intact virion (m. bruns, w. zeller, h. rohdewohld, and f. lehmann ...19883336945
persistent viral infection of the thyroid gland: alteration of thyroid function in the absence of tissue injury.the possible role of viruses as the cause of some thyroid disorders was evaluated in three strains of mice neonatally infected with lymphocytic choriomeningitis virus. we report the first definitive evidence that viruses can persist in the thyroid gland, particularly thyroid epithelial cells in which thyroglobulin is synthesized. concomitant with the infection of these cells was a significant reduction in the level of thyroglobulin mrna and circulating thyroid hormones. another virus that causes ...19883338413
inhibition of diabetes in bb rats by virus infection.bb rats serve as a model for human insulin-dependent diabetes mellitus (iddm), since without insulin treatment, most 60-140-d-old animals die within 1 to 2 wk of developing polyuria, polydypsia, hyperglycemia, and hypoinsulinemia. lymphoid cells accumulate in the islets of langerhans and beta cells undergo destruction. we report that inoculation of such bb rats with lymphocytic choriomeningitis virus (armstrong strain, clone 13) reduces over a prolonged period the incidence of iddm, normalizes t ...19883343348
molecular analysis of viral rnas in mice persistently infected with lymphocytic choriomeningitis virus.infection of newborn mice with lymphocytic choriomeningitis virus (lcmv) results in a lifelong persistent infection. persistently infected animals continuously produce low levels of infectious virus and accumulate large amounts of intracellular viral nucleic acid (p. j. southern, p. blount, and m. b. a. oldstone, nature [london] 312:555-558, 1984). we have used gel electrophoresis and hybridization techniques to analyze viral rnas that appear during the establishment and maintenance of a persist ...19883346946
organ-specific selection of viral variants during chronic infection.this study demonstrates organ specific selection of viral variants during chronic lymphocytic choriomeningitis virus (lcmv) infection in its natural host. isolates with different biological properties were present in the central nervous system (cns) and lymphoid tissues of carrier mice infected at birth with the wt armstrong strain of lcmv. viral isolates from the cns were similar to the wt armstrong strain and induced potent virus-specific cytotoxic t lymphocyte (ctl) responses in adult mice an ...19883367096
tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. evaluation in murine model infections and in patients.to evaluate the potential role of cachectin/tnf-alpha in the pathogenesis of bacterial and viral meningitis, concentrations and kinetics of tnf-alpha were determined in cerebrospinal fluid (csf). after intracerebral, but not systemic, infection with listeria monocytogenes in mice, tnf-alpha was detected as early as 3 h after infection reaching maximum titers after 24 h. however, tnf-alpha was not found in serum during the course of listeria infection. in contrast to bacterial meningitis, no tnf- ...19883367098
effects of persistent lymphocytic choriomeningitis virus infection on cholinergic neurons in the mouse.we have examined the effects of persistent infection with the armstrong e350 strain of lymphocytic choriomeningitis virus (lcmv) on choline acetyltransferase activity in several regions of balb/c mouse brain. despite the presence of high titres of virus in brain for as long as 6 months, and a widespread distribution of virus antigen, no decreases in choline acetyltransferase activity could be demonstrated. the enzyme activity was increased in some regions of brain, showing an effect of the persi ...19883374738
virus-induced immunosuppression: a murine model of susceptibility to opportunistic infection. 19883392416
deleted viral rnas and lymphocytic choriomeningitis virus persistence in vitro.lymphocytic choriomeningitis virus (lcmv) infection of most tissue culture cell lines results in a non-cytopathic persistent infection. persistent infections in vitro share many characteristics with persistent lcmv infection of mice; both are associated with decreased titres of infectious virus, restricted accumulation of viral glycoproteins at the surface of infected cells and the generation of interfering particles. we have used gel electrophoresis and hybridization techniques to analyse lcmv ...19883404118
susceptibility and resistance of inbred strains of syrian golden hamsters (mesocricetus auratus) to wasting disease caused by lymphocytic choriomeningitis virus: pathogenesis of lethal and non-lethal infections.in different strains of inbred syrian golden hamsters (mesocricetus auratus), the lymphocytic choriomeningitis virus (lcmv) strains we and armstrong (arm) produced systemic infection with infective virus and viral antigens detected predominantly in reticuloendothelial organs. host and virus strain-dependent fatal wasting disease also occurred. after infection with we, all mha and pd4 hamsters died of a progressive wasting disease and infectivity persisted in organs at relatively high titres. lsh ...19883411298
host cell-dependent homologous interference in lymphocytic choriomeningitis virus infection.the generation of virus progeny as well as transcription, translation, and replication of the viral small rna (s-rna), which codes for the nucleoprotein (np) and the glycoprotein precursor (gpc), was followed in l and mdck cells after infection with multiplicities (m.o.i.) ranging from 0.01 to 100. in l cells, the yields of both plaque-forming units and interfering particles varied inversely with the m.o.i. northern blot analysis revealed that early after infection with high multiplicity np-mrna ...19883413982
weight loss in obese mice persistently infected with lymphocytic choriomeningitis virus is not associated with elevated tumor necrosis factor/cachectin activity in peritoneal macrophages.c57bl/6 ob/ob (c57 ob/ob) mice infected persistently with lymphocytic choriomeningitis virus (lcmv) show cachexia as judged by a weight loss of greater than 20%. virus persists in a subset of macrophages. because a cachexic state occurs in several chronic debilitating diseases of humans, often accompanied by persistent microbial infections with macrophage/monocytic involvement and tumor necrosis factor (tnf) cachectin production, the role of tnf in the weightloss of ob/ob mice infected persisten ...19883414785
immunohistochemical analysis of the involvement of f4/80 and ia-positive macrophages in mouse liver infected with lymphocytic choriomeningitis virus.the distribution of cells bearing the f4/80 macrophage marker and class ii mhc glycoproteins has been analyzed in the livers of mice infected with viscerotropic lcmv. the number of f4/80+ macrophages in the liver increases greatly during infection. much of this is due to the localization of f4/80+ ia+ monocytes, large numbers of which attach to the walls of the sinuses and the central and hepatic veins. numerous lymphocytes are also observed in the sinusoids, frequently in close association with ...19863464677
biology of cloned cytotoxic t lymphocytes specific for lymphocytic choriomeningitis virus. v. recognition is restricted to gene products encoded by the viral s rna segment.lymphocytic choriomeningitis virus (lcmv) armstrong (arm) strain-specific, h-2d-restricted ctl effectively lyse syngeneic targets infected by lcmv arm, but show reduced killing of lcmv pasteur (past) strain-infected h-2d cells. we have reassorted the two rna segments, large (l) and small (s), of lcmv arm and past to generate lcmv with genotypes of l arm/s past and l past/s arm. by using these reassortants and both lcmv primary ctl and ctl clones, we report that the induction, recognition, and ly ...19863484391
generation of large granular t lymphocytes in vivo during viral infection.cytolytic lymphocytes were isolated from the spleens of lymphocytic choriomeningitis virus (lcmv)-infected mice and were characterized in regards to function, cell size, antigen phenotype, and cell morphology. only 2% of the lyt-2+ cells from uninfected mice were large granular lymphocytes (lgl), whereas 21% of the lyt-2+ cells isolated 7 days postinfection were lgl. the day 7 lyt-2+ populations contained all of the lcmv-specific, class i histocompatibility antigen-restricted cytotoxic t lymphoc ...19863485144
hybrid resistance modulates the inflammatory process induced by lymphocytic choriomeningitis virus-immune t cells.the magnitude of the meningitis occurring 72 hr after adoptive transfer of 8-day lymphocytic choriomeningitis (lcmv)-immune effector t cells from cyclophosphamide-treated or untreated donors into cyclophosphamide-suppressed, lcmv-infected recipients is modified by the hybrid histocompatibility (hh) effect. evidence of inhibition in (h-2kd dd x h-2kb db)f1, as compared with h-2kb db, recipient mice is found for h-2kd db, h-2kd db and (h-2kk db x h-2kb db)f1, but not for (h-2kk dk x h-2kb db)f1 or ...19863485567
effect of rabbit anti-asialo gm1 treatment in vivo or with anti-asialo gm1 plus complement in vitro on cytotoxic t cell activities.the susceptibility of cytotoxic effector lymphocytes and their induction to in vivo or in vitro treatment with rabbit anti-neutral glycolipid ganglio-n-tetraosylceramide (anti-asgm1) antiserum was investigated. intravenous injection of anti-asgm1 antiserum eliminated measurable natural killer (nk) cell activity in spleen cells of mice infected for 5 days with vaccinia virus, or for 8 days with lymphocytic choriomeningitis virus (lcmv) if injected 24 hr prior to testing. in addition, this treatme ...19863486908
the dual role of lymphocytic choriomeningitis virus-specific antibodies. 19863487701
mechanism of action of cyclosporine a on the lymphocytic choriomeningitis virus infection of mice. 19863487702
the effect of lymphocytic choriomeningitis virus-induced suppression of the delayed-type hypersensitivity reaction on virus clearance and pathogenicity. 19863487703
induction of allospecific and virus-specific memory cytotoxic t cells during acute arenavirus infections. 19863487705
numbers of cytolytic t lymphocytes (ctl) and ctl precursor cells in spleens of mice acutely infected with lymphocytic choriomeningitis virus. 19863487706
cloned cytotoxic t cells specific for lymphocytic choriomeningitis virus induce acute disease and primary footpad swelling in infected mice. 19863487709
lymphocytic choriomeningitis virus-induced disease of the central nervous system and the "antigen-sink" hypothesis. 19863487710
immunity to lymphocytic choriomeningitis virus in b cell-depleted mice: evidence for b cell and antibody-independent protection by memory t cells.immunity against lymphocytic choriomeningitis virus (lcmv) in anti-igm-treated b cell-depleted mice was evaluated. we found that the following immune phenomena were independent of antibodies: the generation of virus-specific cytotoxic t cells; the footpad swelling response against locally injected lcmv; natural killer cell activity basic levels or after lcmv or poly(i) x poly(c) stimulation; immunopathologically mediated lcm after primary intracerebral inoculation; immunological memory in lcmv-i ...19863488911
in vivo antiviral effect of cytotoxic t lymphocyte clones specific for lymphocytic choriomeningitis virus.cloned cytotoxic t lymphocytes (ctl) specific for lymphocytic choriomeningitis (lcm) virus are able to eliminate infectious virus from the spleens of lcm virus-infected syngeneic recipient mice upon adoptive transfer. from 4 clones tested, 2 exhibited antiviral activity in vivo. intravenously transferred cloned cells migrated poorly to the spleen of recipient mice, in that only 2% of the injected cells were localized in this organ. based on this rate of homing, it could be shown that the in vivo ...19863489156
t-cell effector function and unresponsiveness in the murine lymphocytic choriomeningitis virus infection. i. on the mechanism of a selective suppression of the virus-specific delayed-type hypersensitivity response.when the virus dose is increased from 10(2) (low dose) to 10(4) ld50 (high dose) a fatal lymphocytic choriomeningitis virus (lcmv) infection is changed into a subclinical one, and a selective virus-specific delayed-type hypersensitivity (dth) unresponsiveness is induced, while the cytotoxic t-cell response remains essentially unchanged. when low-dose spleen effectors were transferred intravenously into intracerebrally infected high-dose mice, fatal lcm disease occurred, which means that infected ...19863489280
t-cell effector function and unresponsiveness in the murine lymphocytic choriomeningitis virus infection. ii. delayed-type hypersensitivity unresponsiveness reflects a defective differentiation from td precursor to effector cell.an increase in the virus dose from 10(2) ld50 (low dose) to 10(4) ld50 (high dose) of lymphocytic choriomeningitis virus (lcmv) results in markedly delayed virus clearance, in spite of a potent cytotoxic t-cell (tc) response. however, virus-specific delayed-type hypersensitivity (dth) reactivity is markedly depressed in high-dose mice, suggesting an association between dth and virus clearance. when virus-primed memory cells are transferred, dth reactivity as well as virus-clearing capacity is re ...19863489281
natural killer cells contribute to inflammation but do not appear to be essential for the induction of clinical lymphocytic choriomeningitis.the inflammatory exudate found in cerebrospinal fluid (csf) of mice 6 days after intracerebral infection with lymphocytic choriomeningitis virus (lcmv) contains substantial populations of both cytotoxic t lymphocytes (ctl) and natural killer (nk) cells. removal of nk cell activity by in vivo treatment with antibody to the asialo gm1 ganglioside and studies with nk-deficient bg/bg mice did not clearly determine whether nk cells contribute in any way to the development of clinical lcm. however, th ...19863489282
t cell-mediated hepatitis in mice infected with lymphocytic choriomeningitis virus. liver cell destruction by h-2 class i-restricted virus-specific cytotoxic t cells as a physiological correlate of the 51cr-release assay?a model for immunologically t cell-mediated hepatitis was established in mice infected with lymphocytic choriomeningitis virus (lcmv). the severity of hepatitis was monitored histologically and by determination of changes in serum levels of the enzymes alanine aminotransferase (alt), aspartate aminotransferase (ast), glutamate dehydrogenase (gldh), and alkaline phosphatase (ap). kinetics of histological disease manifestations, increases of liver enzyme levels in the serum, and cytotoxic t cell a ...19863489805
accumulation of natural killer and cytotoxic t large granular lymphocytes in the liver during virus infection.the immunologic mechanisms involved in virus-induced hepatitis were examined by measuring the cytotoxic capabilities and the morphologic and antigenic phenotypes of leukocytes isolated from livers of virus-infected mice. large granular lymphocytes (lgl) of both natural killer (nk) cell and cytotoxic t lymphocyte (ctl) phenotypes were found to accumulate in livers of mice infected with either the nonhepatotropic armstrong strain of lymphocytic choriomeningitis virus (lcmv-arm) or the hepatotropic ...19863490535
generation in vitro of alloreactive lymphocytes is suppressed by the addition of spleen cells from mice infected with lymphocytic choriomeningitis virus.the generation of cytotoxic t cells to alloantigens in mixed lymphocyte culture was suppressed by the addition of spleen cells from adult mice acutely infected with lymphocytic choriomeningitis virus. t cells of surface phenotype lyt 1+2+ were required for the suppression. suppressive cells appeared also in lymph nodes, but not in the thymus. in the spleen their number was maximal 6 to 8 days after infection. infectious virus could not be detected in the suppressive spleen cells. therefore the v ...19863491276
differential effect of hybrid resistance on the localization of virus-immune effector t cells to spleen and brain.the hybrid resistance (hr) effect operates in the lymphocytic choriomeningitis (lcm) in vivo transfer model to inhibit both the level of cytotoxicity t lymphocyte (ctl) generation in spleen and the induction of inflammation in cerebrospinal fluid (csf). the effect is seen when lcm virus-immune t cells that are homozygous for h-2db are injected into virus-infected, immunosuppressed recipients that are heterozygous for this allele, or into radiation chimeras that express an appropriate f1 phenotyp ...19863491787
characterization of virus-specific cytotoxic t cell clones from allogeneic bone marrow chimeras.we established several h-2-restricted lymphocytic choriomeningitis virus (lcmv)-specific cytotoxic t cell clones from spleens of virus-primed c57bl/6 or c57bl/10 (h-2b) and b10.br (h-2k) mice and from allogeneic c57bl/10----b10.br and b10.br----c57bl/10 bone marrow chimeras. two t cell clones of h-2b origin and restricted to h-2b, 3 of h-2k origin and restricted to h-2k were compared with two clones each derived from the two types of chimeras. their surface phenotype was found to be lyt-2+, l3/t ...19873493906
aberrant t cells in beige mutant mice.cytotoxic t lymphocyte (ctl) morphology and function was examined in beige (bg/bg) mutant mice during infection with lymphocytic choriomeningitis virus (lcmv). virus-specific, class i-restricted ctl activity mediated by total spleen leukocytes isolated from bg/+ or +/+ mice on days 7 or 9 postinfection with lcmv was moderately higher than that mediated by spleen cells isolated from bg/bg mice. the ctl generated in bg/bg mice had aberrant morphology. lyt-2+ cells isolated from bg/+ or +/+ mice ha ...19873494057
mechanism of recovery from acute virus infection: treatment of lymphocytic choriomeningitis virus-infected mice with monoclonal antibodies reveals that lyt-2+ t lymphocytes mediate clearance of virus and regulate the antiviral antibody response.after intravenous infection of mice, lymphocytic choriomeningitis virus multiplied in spleens and livers, attaining highest concentrations on days 4 to 6. the subsequent clearance was as rapid, and 8 to 10 days after inoculation, infectivity was usually below detectability. during the effector phase of virus elimination, both cytotoxic t-cell (ctl) activity and the number of cells producing antiviral antibodies were high. monoclonal antibodies directed against t lymphocytes and t-lymphocyte subs ...19873494855
anti-asialo gm1 eliminates both inflammatory process and cytotoxic t-cell function in the lymphocytic choriomeningitis adoptive transfer model.the induction of severe inflammatory process and fatal neurological disease by transfer of lymphocytic choriomeningitis virus (lcmv)-immune t cells into cyclophosphamide (cy)-suppressed lcmv-infected mice is greatly inhibited by treatment of these recipients with antibody to the asialo gm1 ganglioside (anti-asgm1). examination of cytotoxic activity in lymphoid tissue of the cy-suppressed recipients at 72 hr after cell transfer revealed that anti-asgm1 treatment prevented the development of the c ...19873495344
the acute inflammatory process in murine lymphocytic choriomeningitis is dependent on lyt-2+ immune t cells.virus-immune spleen cells induce fatal immunopathology following adoptive transfer into adult c57b1/6j mice that have been infected with lymphocytic choriomeningitis virus (lcmv) and immunosuppressed with cyclophosphamide. this is accompanied by the development of potent cytotoxic t-lymphocyte (ctl) activity of donor origin in the recipient spleen. both the capacity to trigger the acute meningitis observed at 72 hr and to generate ctl effectors in lymphoid tissue are completely abrogated by the ...19873495350
morphologic analysis of the interactions between lymphocytic choriomeningitis virus-specific cloned cytotoxic t cells and virus infected targets.the interactions between lymphocytic choriomeningitis virus-specific cloned cytotoxic t lymphocytes (ctl) and virus infected targets have been examined by electron microscopy. ctls, which were readily differentiated from target cells by the presence of cytoplasmic granular inclusions, made intimate contact with infected cells. some ctls contacted infected cells via numerous interdigitating processes; others were observed thrusting finger-like protrusions deep into the target cell; some were seen ...19873496491
different tc response profiles are associated with survival in the murine lymphocytic choriomeningitis virus infection.the pathogenicity of lymphocytic choriomeningitis virus (lcmv) inoculated intracerebrally (i.c.) varies with virus strain and dose as well as with the mouse strain used as host. recently, results have indicated that susceptibility to lethal disease correlates directly the ability of the host to produce early and high virus-specific tc activity. however, in the present studies we demonstrate that even though this holds true in many mouse/virus combinations, it does not apply in others. thus, in c ...19873496657
biobreeding/worcester (bb/wor) rats are deficient in the generation of functional cytotoxic t cells.the biobreeding/worcester (bb/wor) rat provides a good model of spontaneous autoimmune diabetes. there are several sublines of the bb/wor rat. the diabetes prone (dp) sublines develop diabetes at a frequency of 50 to 80% from 60 to 120 days of age. the dp rats are lymphopenic, have a severe deficit in phenotypic ox 19+ ox 8+ cytotoxic t cells (tc), and lack rt 6.1 t cells. these rats have a relative increase in ox 19- ox 8+ natural killer (nk) cells and in nk activity as compared with the diabet ...19873497974
chemotactic effect of human recombinant interleukin 2 on mouse activated large granular lymphocytes.human recombinant interleukin 2 (hril-2) was demonstrated in vitro to be chemotactic for mouse large granular lymphocytes (lgl) activated in vivo by virus infection. peritoneal exudate cells harvested from virus-infected mice were used as a source of lgl. lgl collected from mouse hepatitis virus-infected mice at 3 days postinfection were a source for nk 1.1 positive natural killer (nk)/lgl. lgl collected from mice treated with antiserum to gangliotetraosylceramide and infected with lymphocytic c ...19873498769
effective clearance of a persistent viral infection requires cooperation between virus-specific lyt2+ t cells and nonspecific bone marrow-derived cells.the lifelong chronic lymphocytic choriomeningitis virus (lcmv) infection established in neonatally or congenitally infected mice can be eliminated by adoptive transfer of lymphoid cells from lcmv-immune mice. in this study, we have identified the effector cells mediating the clearance of persistent and disseminated lcmv infection. using mice that are recombinant in the h-2 region and by selective depletion of lymphocyte subpopulations, we show that viral clearance was mediated by lcmv-specific l ...19873500329
allogeneic h-2 antigen expression is insufficient for tumor rejection.murine a strain (kkddld) sarcoma i (sai) tumor cells have been transfected with a cloned h-2kb gene. the resulting clones (skb clones) stably express high levels of a molecule that is serologically and biochemically indistinguishable from the h-2kb antigen. skb clones are not susceptible to cytotoxic t lymphocyte-mediated lysis by h-2kb-specific bulk, cloned, or h-2kb-restricted lymphocytic choriomeningitis virus-specific effectors. survival times of a/j and b10.a mice challenged i.p. with the h ...19873500477
studies on immunity to lymphocytic choriomeningitis virus. 19863523184
detection of lymphocytic choriomeningitis virus antibody in colonies of laboratory animals in japan.indirect fluorescent antibody method was applied for a detection of lymphocytic choriomeningitis virus (lcmv) antibody in colonies of laboratory animals in japan. the results showed that the antibody exist in spf mice (3/152, 2.2%) and conventional mice (30/539, 5.6%) with the titers ranging from 1:10 to 1:160. the antibody was also detected in 2.2% (2/89) of syrian hamsters, and 2.9% (2/68) of apodemus agrarius, 21.4% (3/14) of japanese harvest mice which have been maintained as laboratory colo ...19863525200
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