Suppression of acute anti-friend virus CD8+ T-cell responses by coinfection with lactate dehydrogenase-elevating virus.

Friend virus (FV) and lactate dehydrogenase-elevating virus (LDV) are endemic mouse viruses that can cause long-term chronic infections in mice. We found that numerous mouse-passaged FV isolates also contained LDV and that coinfection with LDV delayed FV-specific CD8(+) T-cell responses during acute infection. While LDV did not alter the type of acute pathology induced by FV, which was severe splenomegaly caused by erythroproliferation, the immunosuppression mediated by LDV increased both the severity and the duration of FV infection.

Porcine reproductive and respiratory syndrome virus (PRRSV) infection spreads by cell-to-cell transfer in cultured MARC-145 cells, is dependent on an intact cytoskeleton, and is suppressed by drug-targeting of cell permissiveness to virus infection.

Background: Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiologic agent of PRRS, causing widespread chronic infections which are largely uncontrolled by currently available vaccines or other antiviral measures. Cultured monkey kidney (MARC-145) cells provide an important tool for the study of PRRSV replication. For the present study, flow cytometric and fluorescence antibody (FA) analyses of PRRSV infection of cultured MARC-145 cells were carried out in experiments designed to clarify viral dynamics and the mechanism of viral spread.

Polyclonal hypergammaglobulinemia and formation of hydrophobic immune complexes in porcine reproductive and respiratory syndrome virus-infected and uninfected pigs.

Infection of young conventional, domestic pigs with porcine reproductive and respiratory syndrome virus (PRRSV) strains VR2332 and JA142 resulted in a rapid, progressive increase in serum IgG reaching maximum levels of 20-30 mg/mL at about 3 weeks post infection (p.i.), which were maintained until at least 63 days p.

Lactate dehydrogenase-elevating virus induces apoptosis in cultured macrophages and in spinal cords of C58 mice coincident with onset of murine amyotrophic lateral sclerosis.

Age-dependent poliomyelitis (ADPM) or murine amyotrophic lateral sclerosis (ALS) is a murine paralytic disease triggered in immunosuppressed genetically-susceptible mice by infection with the arterivirus lactate dehydrogenase-elevating virus (LDV). This disease provides an animal model for ALS, affecting anterior horn neurons and resulting in neuroparalysis 2-3 weeks after LDV infection. We have tested the hypothesis that spinal cord apoptosis is a feature of the LDV-induced murine ALS, since apoptosis is postulated to be a causal factor in human ALS.

Hydrophobic IgG-containing immune complexes in the plasma of autoimmune MRL/lpr mice, lactate dehydrogenase-elevating virus-infected mice, and pigs: association with transforming growth factor-beta and pH-dependent amplification.

Persistent infection of mice with lactate dehydrogenase-elevating virus (LDV) is associated with polyclonal B cell activation, autoimmunity, and circulating hydrophobic IgG-containing immune complexes (ICs), which bind to the surfaces of uncoated ELISA plates in the presence of 0.05% Tween 20. We demonstrate here that hydrophobic IgG-containing ICs also appear naturally in the plasma of autoimmune MRL/lpr mice.

Glucocorticoid regulation of lactate dehydrogenase-elevating virus replication in macrophages.

Lactate dehydrogenase-elevating virus (LDV) is a macrophage-tropic arterivirus which generally causes a persistent viremic infection in mice. LDV replication in vivo seems to be primarily regulated by the extent and dynamics of a virus-permissive macrophage population. Previous studies have shown that glucocorticoid treatment of chronically LDV-infected mice transiently increases viremia 10-100-fold, apparently by increasing the productive infection of macrophages.

Current concepts in multiple sclerosis: Part II.

Multiple sclerosis (MS) is a complex and challenging autoimmune disease of the central nervous system, affecting approximately 0.1% of the US population. Evidence to date suggests that viral infection triggers autoimmune attack against nerve cells in genetically-susceptible individuals.

Current concepts in multiple sclerosis: Part I.

Multiple sclerosis (MS) is a complex and challenging autoimmune disease of the central nervous system, affecting approximately 0.1% of the US population. Evidence to date suggests that viral infection triggers autoimmune attack against nerve cells in genetically-susceptible individuals.

Transplacental lactate dehydrogenase-elevating virus (LDV) transmission: immune inhibition of umbilical cord infection, and correlation of fetal virus susceptibility with development of F4/80 antigen expression.

Maternal-to-fetal transmission of the murine lactate dehydrogenase-elevating virus (LDV) has been previously shown to be regulated by maternal immunity as well as gestational age. For the present study, the role of maternal immunity in placental and umbilical cord virus protection was studied, and virus targeting of umbilical cord and fetal macrophages was correlated with expression of the F4/80 macrophage phenotypic marker. The results showed that LDV-infected macrophages appeared in umbilical cord by 24 h post-infection of pregnant mice, and some LDV-infected macrophages displayed the F4/80 phenotype.

Age-dependent poliomyelitis in mice is associated with respiratory failure and viral replication in the central nervous system and lung.

Age-dependent poliomyelitis (ADPM) is a virally induced neuroparalytic disease of mice and a model for amyotrophic lateral sclerosis (ALS). ADPM is triggered in genetically susceptible mice by immunosuppression and infection with lactate dehydrogenase-elevating virus (LDV). Both ADPM and ALS are characterized by progressive degeneration of anterior horn motor neurons, and death in ALS is usually associated with respiratory failure.

N-glycans on the short ectodomain of the primary envelope glycoprotein play a major role in the polyclonal activation of B cells by lactate dehydrogenase-elevating virus.

The common biologically cloned isolates of lactate dehydrogenase-elevating virus (LDV-P and LDV-vx) invariably cause a polyclonal activation of B cells in immunocompetent mice. It is recognized by an at least 10-fold increase in plasma IgG2a levels and the de novo formation of immune complexes that most likely consist of autoantibodies and their antigens. The present study indicates that three closely spaced N-glycans on the short ectodomain of the primary envelope glycoprotein, VP-3P, of LDV-P/vx, play a major role in inducing the polyclonal proliferation of B cells.

Regulation of immune complexes during infection of mice with lactate dehydrogenase-elevating virus: studies with interferon-gamma gene knockout and tolerant mice.

Mice persistently infected with lactate dehydrogenase-elevating virus (LDV) develop circulating IgG-containing hydrophobic immune complexes, with a molecular mass of 150 to 300 kd, which bind to the surfaces of high-capacity enzyme-linked immunosorbent assay (ELISA) plates. LDV infection also stimulates polyclonal B-cell activation and autoimmunity. For this study, interferon-gamma gene knockout (GKO) mice were utilized to study circulating immune complexes and other parameters of LDV infection.

Inhibition of virus-induced age-dependent poliomyelitis by interferon-gamma.

Age-dependent poliomyelitis (ADPM) is a neuroparolytic disease which results from combined infection of susceptible mice with lactate dehydrogenase-elevating virus (LDV) and murine leukemia virus (MuLV). The present study examined the effects of interferon-gamma (IFN-gamma) treatment on the incidence of ADPM, replication of LDV and MuLV and anti-LDV immunity. IFN-gamma treatment of ADPM-susceptible C58/M mice protected them from paralytic disease, but had no detectable effect on the IgG anti-LDV response or LDV viremia.

Trojan Horse macrophages: studies with the murine lactate dehydrogenase-elevating virus and implications for sexually transmitted virus infection.

Previous studies have suggested that monocytes or macrophages may mediate internal virus spread. For the present study, the tissue distribution and infectious potential of dye-labelled and/or lactate dehydrogenase-elevating virus (LDV)-infected murine macrophages were determined. Murine peritoneal macrophages were labelled with the fluorescent carbocyanine tracking dye Dil, injected into mice, and the tissue distribution of Dil-labelled cells was determined by fluorescence analysis of frozen sections.

Determination of the viremia threshold for dental cross-infection in a mouse model.

An animal model of dental virus transmission was developed using the lactate dehydrogenase-elevating virus (LDV) of mice to study cross infection. Mouse-to-mouse cross-infection was carried out by scaling the teeth of LDV-infected donor mice with dental instruments, immediately prior to using the contaminated instruments on the teeth of recipient indicator mice. The level of donor viremia was found to correlate with the rate of virus cross-infection, with a viremia threshold level of 10(7.

Regulation of transplacental virus infection by developmental and immunological factors: studies with lactate dehydrogenase-elevating virus.

Placental and fetal infections with lactate dehydrogenase-elevating virus (LDV) were determined by virus titration, indirect fluorescence antibody (IFA), and in situ hybridization with cDNA probes. Experiments were designed to determine the effects of gestational age, timing of maternal LDV infection, and immunological (antibody and cytokine) factors on mouse placental and fetal LDV infection. Virus infection of the placenta was detected at high levels (almost all placentas infected) within 24 h post-maternal infection (p.

Effectiveness of ultrasonic cleaning of dental instruments.

Purpose: To quantitate blood contamination present on dental instruments used for routine prophylaxis and to assess the effectiveness of ultrasonic decontamination in reducing blood and virus contamination on dental instruments.

Materials And Methods: Human blood contamination present on dental instruments obtained after routine prophylaxis was analyzed using IgG as a blood marker.

Results: The estimated contaminating blood volume was found to normally range between 1.

Cytokine regulation of lactate dehydrogenase-elevating virus: inhibition of viral replication by interferon-gamma.

The mechanisms which regulate the replication of lactate dehydrogenase-elevating virus (LDV), a persistent murine model virus which infects macrophages, are unclear. For this study, the effects of murine recombinant interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) on LDV replication were examined. LDV permissiveness was reduced in macrophages obtained from uninfected mice treated with IFN-gamma prior to cell harvest and in vitro LDV infection.

Immunoglobulin transfer from immune-reconstituted SCID mice to nursing neonates: blood distribution of antibody and association with perinatal virus protection.

Previous work in our laboratory has shown that fetal protection from maternal transmission of the murine lactate dehydrogenase-elevating virus (LDV) infection is mediated by adoptive transfer of maternal anti-viral immunity. In the present report, we have characterized reconstitution of immunity in immunodeficient SCID mice following transplantation with BALB/c spleen cells, and studied the fate and distribution of maternally-derived antibodies after passage to neonatal SCID mice by nursing. Immune-reconstituted SCID mice maintained stable immunity for up to 7 months post-transplantation, during which time they produced nonneutralizing IgG anti-LDV antibodies and protected their offspring from maternally-derived LDV infection.

Virucidal effect of murine duodenal extracts: studies with lactate dehydrogenase-elevating virus.

Mucosal resistance to infection with lactate dehydrogenase-elevating virus (LDV) has been previously demonstrated, and the LDV system presents an important murine model for the study of mucosal barriers to viral infection. In the present study, duodenal molecules were isolated from normal mice which had potent virucidal activity, when tested against LDV as well as canine herpes, canine hepatitis, Semliki forest, and visna viruses. The virucidal activity was demonstrated to be non-immune in nature, and was present in apparently non-enzymatic protein molecules, having a molecular mass of between 10-100 kDa by membrane filtration and 10-17 kDa by gel filtration.

Regulation of maternal-fetal virus transmission in immunologically reconstituted SCID mice infected with lactate dehydrogenase-elevating virus.

Immunodeficient SCID (C.B-17 scid/scid) mice with persistent lactate dehydrogenase-elevating virus (LDV) infection failed to produce IgG anti-LDV antibodies, and during chronic infection transmitted virus infection to 95% of their offspring. In contrast, normal mice infected 15 or more days prior to giving birth produced IgG anti-LDV antibodies and transmitted LDV infection to only 0-46% of their fetuses.

Infection of SCID mice with lactate dehydrogenase-elevating virus stimulates B-cell activation.

Mice of the C.B-17 strain homozygous for the scid mutation (SCID mice) were infected with lactate dehydrogenase-elevating virus (LDV), and plasma samples obtained at intervals up to 42 days postinfection were analyzed for total immunoglobulins, anti-LDV antibodies, virus-specific immune complexes, and viremia levels. The mice responded to LDV infection with transient increases in total blood IgM, production of IgM-antigen complexes and IgM anti-LDV, as well as increased blood IgG2a.

Enhancement of murine susceptibility to oral lactate dehydrogenase-elevating virus infection by non-steroidal anti-inflammatory agents, and antagonism by misoprostol.

The murine lactate dehydrogenase-elevating virus (LDV) was used to study the effects of prostaglandin-acting agents on mucosal resistance to virus infection. Mice treated with non-steroidal anti-inflammatory drugs (NSAIDs) prior to oral exposure to LDV demonstrated a reduction in the mucosal barrier to LDV infection. Histological studies indicated that these NSAID effects were not a result of gross or microscopic tissue damage.

Analysis of immunoglobulin isotype blood levels, splenic B-cell phenotypes, and spleen cell immunoglobulin gene expression in mice infected with lactate dehydrogenase-elevating virus.

B-lymphocyte activation was studied in mice infected with lactate dehydrogenase-elevating virus (LDV). ELISA determinations of blood total immunoglobulin levels demonstrated that, at 10 days post-infection (p.i.