Abstract: The present invention relates to the human cellular protein glutathione peroxidase-gastrointestinal as a target for medical intervention against Hepatitis C virus (HCV) infections. Furthermore, the present invention relates to a method for the detection of compounds useful for prophylaxis and/or treatment of Hepatitis C virus infections and a method for detecting Hepatitis C virus infections in an individual or in cells. Also compositions, compounds, nucleic acid molecules (such as aptamers), mono- or polyclonal antibodies are disclosed which are effective for the treatment of HCV infections, and methods for prophylaxis and/or treatment of Hepatitis C virus infections or for the regulation of Hepatitis C virus production are disclosed.

Abstract: The combination of HIV proteins Tat and Nef is chemotactic for CD4+ cells. Utilizing the capacity of Tat and Nef to modulate CD4+ cell trafficking and infiltration, the invention provides various treatment modes for individuals infected with HIV. The invention further provides treatment modes for other localized diseases by controlling CD4+ cell trafficking and infiltration. In particular, the invention provides methodology for promoting CD4+ cell chemotaxis to a localized site of infection as a means of augmenting the efficacy of extant chemotherapeutic methods. The invention further provides methodology for diverting CD4+ cell infiltration from a localized site where the presence of CD4+ cells is detrimental to the clinical outcome, by providing a composition comprising Tat and Nef at a distinct site, such as blood, within the individual where the accumulation of CD4+ cells is less detrimental.

Abstract: A promoter domain of 1816 bp or 441 bp in the upstream side of exon 1B of IAI.3B gene has a specifically high promoter activity in ovarian cancer cells. An adenovirus having this promoter domain inserted in the E1 domain thereof exhibits a specifically high cell proliferation inhibitory effect on ovarian cancer cells. Thus, it is efficacious in gene therapy for ovarian cancer.

Abstract: Monoclonal antibodies to thymidine kinase 1 are disclosed which are useful in methods of detecting, diagnosing, and treating viral infection.

Abstract: The present invention provides a method of diagnosing neoplasms having a particular phenotype by using oncolytic viruses that selectively replicate in neoplasms having the particular phenotype. For example, reovirus does not replicate in normal cells. However, reovirus selectively replicate in cells with an activated ras pathway, which leads to death of these cells. Therefore, a cell which becomes neoplastic due to, at least in part, elevated ras pathway activities can be diagnosed by its susceptibility to reovirus replication. This invention can further be applied, using other oncolytic viruses, to the diagnosis and/or treatment of other tumors, such as interferon-sensitive tumors, p53-deficient tumors and Rb-deficient tumors. Kits useful in the diagnosis or treatment disclosed herein are also provided.

Abstract: Aspects of the present invention relate to the discovery of a novel hepatitis C virus (HCV) isolate. Embodiments include HCV peptides, nucleic acids encoding said HCV peptides, antibodies directed to said peptides, compositions containing said nucleic acids and peptides, as well as methods of making and using the aforementioned compositions including, but not limited to, diagnostics and medicaments for the treatment and prevention of HCV infection.

Abstract: The present invention provides a replication competent hepatitis C virus that includes a heterologous polynucleotide. The invention also includes methods for modifying a hepatitis C virus polynucleotide, selecting a replication competent hepatitis C virus polynucleotide, detecting a replication competent hepatitis C virus polynucleotide, and identifying a compound that inhibits replication of a hepatitis C virus polynucleotide.

Abstract: This invention provides cellular gene products which have anti-apoptotic activity in HIV-1 infected cells. Other pro-apoptotic genes and methods of use thereof are also disclosed. The compositions of the invention may be used to advantage to develop novel therapeutic agents for the treatment of HIV infection. The compositions of the invention may also be used to advantage to develop novel therapeutic agents for the treatment of disorders associated with inordinate cellular apoptosis.

Abstract: The present invention relates to compositions comprising a novel recombinant virus which replicates selectively in cells or tissues that are hypoxic or have an activated HIF pathway. The novel compositions of the invention comprise a recombinant virus genetically engineered to have a hypoxia/HIF-responsive element, or a multiplicity of such elements, operably linked to a promoter which is in turn operably linked to a nucleic acid(s) encoding a peptide(s) which regulates or modulates replication of the virus and/or encode a therapeutic molecule. The invention also includes constructs useful for screening of agents which interact with proteins or genes in the hypoxia-inducible pathway or are jointly translated under hypoxia and animal models useful for monitoring a variety of hypoxic conditions in a non-invasive manner.

Abstract: The invention provides a method of activating hepatitis C virus (HCV)-specific T cells, including CD4+ and CD8+ T cells. HCV-specific T cells are activated using fusion proteins comprising HCV NS3, NS4, NS5a, and NS5b polypeptides, polynucleotides encoding such fusion proteins, or polypeptide or polynucleotide compositions containing the individual components of these fusions. The method can be used in model systems to develop HCV-specific immunogenic compositions, as well as to immunize a mammal against HCV.

Abstract: A DNA vaccine effective for eliciting an immune response against cells that present a carcinoembryonic antigen (CEA) comprises a DNA operably encoding a CEA and a DNA operably encoding a CD40 ligand, SEQ ID NO:1 and SEQ ID NO: 2, respectively, or its homotrimer, CD40LT. The DNA vaccine can be incorporated in a delivery vector such as an attenuated live bacterium or virus, or a liposome carrier. In a method embodiment, the DNA vaccine is administered orally to a mammal, such as a human, to elicit an immune response against CEA presenting cells such as colon cancer cells. A preferred method embodiment includes the additional step of treating the mammal with recombinant antibody fusion protein huKS1/4-IL2 to enhance the immune response effectiveness of the vaccine.

Abstract: Data consistent with autoimmune disease being caused by Epstein-Barr virus are shown. Based on this evidence, an effective vaccine would prevent the autoimmune disease in those vaccinated, modified or administered so that the vaccine is not itself capable of inducing autoimmune disease. In the case of anti-Sm, structures to be avoided in an Epstein-Barr virus-derived vaccine have been identified. Differences have been identified in the immune responses to Epstein-Barr infection between individuals who develop a specific autoimmune disease and those who do not. These differences are used to distinguish those who are at greater risk for developing specific autoimmune diseases from those who are a lesser risk. Assuming Epstein-Barr virus causes autoimmune disease and that Epstein-Barr virus remains latent in the patient for life, reactivation of the virus from the latent state is important in generating or maintaining the autoimmune response that culminates in autoimmune disease.

Abstract: The present invention relates to modulating the nature and/or level of an immune response to a molecule. In particular, the invention relates to effecting an increase in the TH1 immune response to molecules such as, but not limited to, antigens or immunogens. The invention also relates to reducing a TH2 immune response to molecules. More particularly, the invention relates to altering the level of TH1- and TH2-associated immunoglobulins, the level of proliferation of TH1- and TH2-associated cytokines, and the level of proliferation of TH1 and TH2 cells.

Abstract: The application discloses novel polypeptides and nucleic acids involved in a variety of biological processes, including viral reproduction. Related methods and compositions are also described.

Abstract: A method for producing a refolded, inactive form of recombinantly produced NS2/3 protease which comprises the steps of: a) purifying the protease from inclusion bodies in the presence of a chaotropic agent; and b) refolding the purified protease by contacting it with a reducing agent and lauryldiethylamine oxide (LDAO) in the presence of reduced concentration of chaotropic agent or polar additive. The invention further comprises a method for activating this refolded inactive NS2/3 protease by adding an activation detergent. This method produces large amounts of the active NS2/3 protease to allow small molecules and ligands to be screened as potential inhibitors of NS2/3 protease, which may be useful as therapeutic agents against HCV.

Abstract: The present invention relates to a method of increasing the sensitivity of neoplastic cells to chemotherapeutic agents by using a virus, a method of treating proliferative disorders with a virus and chemotherapeutic agents, and a method for preventing a neoplasm from developing drug resistance to chemotherapeutic agents. The virus is preferably a reovirus.

Abstract: Methods for separating AAV empty capsids from mixtures of AAV vector particles and AAV empty capsids are described. The methods use column chromatography techniques and provide for commercially viable levels of recombinant AAV virions.

Abstract: A process for propagating a mutant herpes virus having a mutation in its endogenous HSV VP16 gene or a homologue thereof, which process comprises infecting a cell line with the mutant herpes virus and culturing the cell line, wherein the cell line comprises a nucleic acid sequence encoding a functional herpes simplex virus (HSV) VP16 polypeptide, or a homologue thereof, operably linked to a control sequence permitting expression of the polypeptide in said cell line; the nucleic acid sequence being (i) capable of complementing the endogenous gene and (ii) unable to undergo homologous recombination with the endogenous gene. In addition, the present invention provides cell lines which can be used for the growth of mutant herpes viruses which have defects in certain immediate early genes together with mutations in VP16 or homologue thereof.

Abstract: The present invention relates to compositions and methods for enhancing the effect of vaccines in animals, such as domestic, sport, or pet species, and humans. More particularly, the use of Ribavirin as an adjuvant to a vaccine protocol and compositions having Ribavirin and an antigen are described.

Abstract: The present invention relates to use of bicistronic DNA constructs for identifying compounds that inhibits IRES-dependent translation activity of an infectious enterovirus (EV) or encephalomyocarditis virus (EMCV) without affecting CAP-dependent translation activity of a host subject. The compounds thus identified are useful in preparation of a medicament for treating EV or EMCV infection.