Verrastro T, Lorenzi TF, Wendel-Neto S (1996) Hematologia – Hemoterapia

Verrastro T, Lorenzi TF, Wendel-Neto S (1996) Hematologia – Hemoterapia. the two strains to infer the conservation of these immunological determinants. This assessment Mouse monoclonal to NFKB1 was also applied to the experimentally identified CD8+ T cell-restricted epitope of the DENV2 NS1 protein, AGPWHLGKL (Gao et al., 2008). b Expected epitopes with higher scores within the EIII/NS1 region of the JHA1 isolate and the CD8+ T cell-restricted epitope of the DENV2 BML-275 (Dorsomorphin) NS1 protein, all of which were fully conserved between the JHA1 and NGC strains. c Location of the conserved epitope within the EIII/NS1 region of the strains subjected to the BML-275 (Dorsomorphin) analysis. d Epitope located in the NS1 protein previously demonstrated to be specific for CD8+ T lymphocytes and widely conserved among several DENV2 strains.(DOC) pone.0044984.s003.doc (29K) GUID:?6E88E49D-6902-45FB-A226-E7B2100D2AF2 Abstract Dengue computer virus (DENV) is the causative agent of dengue fever (DF), a mosquito-borne illness endemic to tropical and subtropical regions. There is currently no effective drug or vaccine formulation for the prevention of DF and its more severe forms, i.e., dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). You will find two generally available experimental models for the study of DENV pathogenicity as well as the evaluation of potential vaccine candidates. The 1st model consists of nonhuman primates, which do not develop symptoms but rather a transient viremia. Second, mouse-adapted computer virus strains or immunocompromised mouse lineages are utilized, which display some of the pathological features of the infection observed in humans but may not be relevant to the results with regard to the wild-type initial computer virus strains or mouse lineages. In this study, we describe a genetic and pathological study of a DENV2 medical isolate, named JHA1, which is BML-275 (Dorsomorphin) definitely naturally capable BML-275 (Dorsomorphin) of infecting and killing Balb/c mice and reproduces some of the symptoms observed in DENV-infected subjects. Sequence analyses shown the JHA1 isolate belongs to the American genotype group and bears genetic markers previously associated with neurovirulence in mouse-adapted computer virus strains. The JHA1 strain was lethal to immunocompetent mice following intracranial (i.c.) inoculation having a LD50 of approximately 50 PFU. Mice infected with the JHA1 strain lost excess weight and exhibited general tissue damage and hematological disturbances, with similarity to the people symptoms observed in infected humans. In addition, it was demonstrated the JHA1 strain shares immunological determinants with the DENV2 NGC research strain, as evaluated by cross-reactivity of anti-envelope glycoprotein (website III) antibodies. The present results indicate the JHA1 isolate may be a useful tool in the study of DENV pathogenicity and will help in the evaluation of anti-DENV vaccine formulations as well as potential restorative approaches. Introduction Illness with one of the four dengue computer virus (DENV) serotypes can be asymptomatic or can result in a wide spectrum of medical manifestations. The disease may yield symptoms ranging from a slight acute febrile illness, termed dengue fever (DF), to the more severe types of the disease that include dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), characterized by fever, hemorrhage, thrombocytopenia, vascular leakage and viremia that is 10- to 100-fold greater than in DF [1]. The cellular and molecular mechanisms involved in DENV pathogenesis remain, at least in part, elusive. The current hypotheses concerning the mechanisms involved in dengue pathogenicity and the severity of disease BML-275 (Dorsomorphin) symptoms range from dysfunction of the sponsor immune system, with the generation of cross-reactive antibodies and T cells, to platelet depletion, endothelial cell apoptosis and match activation with damage to sponsor cells [2]C[7]. The general health state and genetic profile of the sponsor as well as the virulence variability among the DENV strains contribute to the severity of the disease symptoms and development of DHF/DSS [8]C[11]. However, the lack of a more appropriate animal model for the study of the disease is a definite drawback to determining DENV pathogenesis and the immunological mechanisms involved in the disease progression or safety [12]. Like a corollary, no effective.