ABSTRACT
To examine whether a retroviral disease can be controlled in animals in which cells from a resistant strain coexist in a state of immunological tolerance with cells from a susceptible strain, allophenic mice were constructed and infected with LP-BM5 murine leukemia viruses which induce a fatal disorder, termed murine acquired immunodeficiency syndrome (MAIDS), characterized by lymphoproliferation and immunodeficiency in susceptible inbred strains of mice. We found that in two different strain combinations, resistance to MAIDS was contingent on the presence in individual animals of >50% of lymphocytes of resistant strain origin and correlated with reduction or elimination of retrovirus. In contrast, animals harboring substantial, but less than predominant, numbers of genetically resistant lymphocytes developed disease and died within the same time frame as susceptible control mice with uncontained proliferation of retrovirus.
Subject(s)
Chimera/immunology , Murine Acquired Immunodeficiency Syndrome/immunology , Animals , Blastocyst , Disease Susceptibility , Immune Tolerance , Immunity, Innate , Leukemia Virus, Murine , Lymphocyte Activation , Mice , Mice, Inbred A , Mice, Inbred Strains , Murine Acquired Immunodeficiency Syndrome/physiopathology , Species Specificity , Splenomegaly , Stem Cells , Time FactorsABSTRACT
Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis, apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining coordinated gene expression profiles but are also highly effective for molecularly "fingerprinting" diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious disease pathogenesis.
Subject(s)
Gene Expression Profiling , Liver Diseases/genetics , Oligonucleotide Array Sequence Analysis/methods , Animals , Apoptosis/genetics , Eosinophils/pathology , Fibrosis , Genotype , Hydroxyproline/metabolism , Inflammation/etiology , Inflammation/genetics , Inflammation/mortality , Inflammation Mediators/metabolism , Interleukin-10/deficiency , Interleukin-10/genetics , Interleukin-12/deficiency , Interleukin-12/genetics , Interleukin-4/deficiency , Interleukin-4/genetics , Liver/metabolism , Liver/pathology , Liver Diseases/etiology , Liver Diseases/mortality , Macrophages/pathology , Mice , Mice, Knockout , Neutrophil Infiltration , Neutrophils/pathology , Schistosoma mansoni/growth & development , Schistosomiasis mansoni/complications , Schistosomiasis mansoni/parasitology , Survival Rate , Time FactorsABSTRACT
Immune activation in murine AIDS (MAIDS) has been suggested to involve a superantigen (SAG). The possibility that SAGs encoded by mammary tumor virus (MTV) might be the source of stimulation was studied by using Mtv mice. Mtv- mice developed typical MAIDS, excluding a requirement for Mtv-encoded SAGs in the pathogenesis of this disorder.
Subject(s)
Antigens, Viral/immunology , Leukemia Virus, Murine/immunology , Murine Acquired Immunodeficiency Syndrome/immunology , Superantigens/immunology , Animals , Cell Line , Female , Male , Mammary Tumor Virus, Mouse/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred CBAABSTRACT
We have constructed a recombinant baculovirus containing a 4.0-kilobase dengue virus cDNA sequence that codes for the three virus structural proteins, capsid (C) protein, premembrane (PreM) protein, and envelope glycoprotein (E), and nonstructural proteins NS1 and NS2a. Infection of cultured Spodoptera frugiperda cells with this recombinant virus resulted in the production of E and NS1 proteins that were similar in size to the corresponding viral proteins expressed in dengue virus-infected simian cells. Other dengue virus-encoded proteins such as PreM and C were also synthesized. Rabbits immunized with the dengue virus protein products of the recombinant virus developed antibodies to PreM, E, and NS1, although the titers were low, especially to PreM and E. Nevertheless, the dengue virus antigens produced by the recombinant virus induced resistance in mice to fatal dengue encephalitis.