Abstract: Alterations of certain metabolite concentrations and fluxes that occur in response to viral infection are described. Host cell enzymes in the involved metabolic pathways are selected as targets for intervention; i.e., to restore metabolic flux to disadvantage viral replication, or to further derange metabolic flux resulting in “suicide” of viral-infected cells (but not uninfected cells) in order to limit viral propagation. While any of the enzymes in the relevant metabolic pathway can be selected, pivotal enzymes at key control points in these metabolic pathways are preferred as candidate antiviral drug targets. Inhibitors of these enzymes are used to reverse, or redirect, the effects of the viral infection. Drug candidates are tested for antiviral activity using screening assays in vitro and host cells, as well as in animal models. Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. The antiviral activity of enzyme inhibitors is demonstrated.

Abstract: Immunogenic compositions and prophylactic or therapeutic vaccines for use in protecting and treating against human cytomegalovirus (CMV) are disclosed. Subunit vaccines comprising a human CMV protein complex comprising pUL128 or pUL130, and nucleic acid vaccines comprising at least one nucleic acid encoding a CMV protein complex comprising pUL128 or pUL130 are described. Also disclosed are therapeutic antibodies reactive against a CMV protein complex comprising pUL128 or pUL130, as well as methods for screening compounds that inhibit CMV infection of epithelial and endothelial cells, methods for immunizing a subject against CMV infection, methods for determining the capability of neutralizing antibodies to inhibit CMV infection of cell types other than fibroblasts, and methods of diminishing an CMV infection.

Abstract: Methods of increasing diversity in cytomegalovirus vaccines through the selection of cell type in which the virus is propagated, and the use of cytomegalovirus produced by those methods in the development of vaccine compositions, are disclosed. Vaccine compositions comprising CMV isolated from epithelial cells are also disclosed.

Abstract: Immunogenic compositions and prophylactic or therapeutic vaccines for use in protecting and treating against human cytomegalovirus (CMV) are disclosed. Subunit vaccines comprising a human CMV protein complex comprising pUL128 or pUL130, and nucleic acid vaccines comprising at least one nucleic acid encoding a CMV protein complex comprising pUL128 or pUL130 are described. Also disclosed are therapeutic antibodies reactive against a CMV protein complex comprising pUL128 or pUL130, as well as methods for screening compounds that inhibit CMV infection of epithelial and endothelial cells, methods for immunizing a subject against CMV infection, methods for determining the capability of neutralizing antibodies to inhibit human CMV infection of cell types other than fibroblasts, and methods of diminishing an CMV infection.

Abstract: Alterations of certain metabolite concentrations and fluxes that occur in response to viral infection are described. Host cell enzymes in the involved metabolic pathways are selected as targets for intervention; i.e., to restore metabolic flux to disadvantage viral replication, or to further derange metabolic flux resulting in “suicide” of viral-infected cells (but not uninfected cells) in order to limit viral propagation. While any of the enzymes in the relevant metabolic pathway can be selected, pivotal enzymes at key control points in these metabolic pathways are preferred as candidate antiviral drug targets. Inhibitors of these enzymes are used to reverse, or redirect, the effects of the viral infection. Drug candidates are tested for antiviral activity using screening assays in vitro and host cells, as well as in animal models. Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. The antiviral activity of enzyme inhibitors is demonstrated.

Abstract: An algorithm for identification of microRNA (miRNA) targets within viral and cellular RNA is disclosed. Also disclosed are essential herpes virus genes whose transcripts contain one or more targets of miRNAs encoded by herpes viruses or by host cells as predicted by the algorithm, and the use of such targets, miRNAs and their derivatives for modulating viral replication and latency.

Abstract: Immunogenic compositions and prophylactic or therapeutic vaccines for use in protecting and treating against human cytomegalovirus (CMV) are disclosed. Subunit vaccines comprising a human CMV protein complex comprising pUL128 or pUL130, and nucleic acid vaccines comprising at least one nucleic acid encoding a CMV protein complex comprising pUL128 or pUL130 are described. Also disclosed are therapeutic antibodies reactive against a CMV protein complex comprising pUL128 or pUL130, as well as methods for screening compounds that inhibit CMV infection of epithelial and endothelial cells, methods for immunizing a subject against CMV infection, methods for determining the capability of neutralizing antibodies to inhibit human CMV infection of cell types other than fibroblasts, and methods of diminishing an CMV infection.

Abstract: Certain human genes have been found to be induced or repressed in host cells infected with HCMV. A large set of such genes has been identified. These have diagnostic use in determining the extent of tissue damage caused by the infection as well as in determining the stage of disease progression of the HCMV infection. Such genes are likely those involved in mediating the pathology of the infected tissues. Thus by identifying agents which are able to reverse the induction or repression of such genes, one can find candidate therapeutic agents for use in treating and or preventing HCMV-caused disease pathologies.

Abstract: The present invention relates to a method for producing helper-free stocks of recombinant adeno-associated virus (rAAV) which can be used to efficiently and stably transduce foreign genes into host cells or organisms. The method comprises the cotransfection of eukaryotic cells with rAAV and with helper AAV DNA in the presence of helper virus (e.g. adenovirus or herpesvirus) such that the helper AAV DNA is not associated with virion formation. The crux of the invention lies in the inability of the helper AAV DNA to recombine with rAAV vector, thereby preventing the generation of wild-type virus. In a specific embodiment of the invention, the vector comprises a recombinant AAV genome containing only the terminal regions of the AAV chromosome bracketing a non-viral gene, and the helper AAV DNA comprises a recombinant AAV genome containing that part of the AAV genome which is not present in the vector, and in which the AAV terminal regions are replaced by adenovirus sequences.

Abstract: Certain human genes have been found to be induced or repressed in host cells infected with HCMV. A large set of such genes has been identified. These have diagnostic use in determining the extent of tissue damage caused by the infection as well as in determining the stage of disease progression of the HCMV infection. Such genes are likely those involved in mediating the pathology of the infected tissues. Thus by identifying agents which are able to reverse the induction or repression of such genes, one can find candidate therapeutic agents for use in treating and or preventing HCMV-caused disease pathologies.

Abstract: Assays for determining the downstream effects of drugs that modulate the function of transcription regulatory proteins are disclosed. The assays comprise the steps of (a) providing cells that contain the transcription factor; (b) maintaining a control population and a test population of the cells under conditions that allow gene expression to occur in the cells, wherein the test population is exposed to the agent that modulates the activity of the transcription factor; (c) generating a gene expression profile for each of the control population and the test population of cells; and (d) comparing the gene expression profile from the control population of cells with the gene expression profile from the test population of cells; those differences being attributable to the effect of the agent that modulates the activity of the transcription factor.

Abstract: Novel pharmaceutical compositions and treatment methods are disclosed for chemokine-mediated inflammatory and immune-related pathological conditions. The pharmaceutical preparation comprises a chemokine binding activity from a supernatant of human cytomegalovirus (HCMV)-infected cells involving the secreted HCMV UL21.5 protein or functional fragment thereof and capable of binding the chemokine RANTES. Methods of treatment comprise administering a therapeutically effective amount of the UL21.5 activity-containing pharmaceutical preparation.

Abstract: Certain human genes have been found to be induced or repressed in host cells infected with HCMV. A large set of such genes has been identified. These have diagnostic use in determining the extent of tissue damage caused by the infection as well as in determining the stage of disease progression of the HCMV infection. Such genes are likely those involved in mediating the pathology of the infected tissues. Thus by identifying agents which are able to reverse the induction or repression of such genes, one can find candidate therapeutic agents for use in treating and or preventing HCMV-caused disease pathologies.

Abstract: Multiple binding sites for the transcription factors MAZ and Sp1 within the adenovirus type 5 major late promoter have been identified by DNase I protection studies. In the proximal region of the promoter, both MAZ and Sp1 interact with GC-rich sequences flanking the TATA box. Two MAZ binding sites are centered at −18 and −36 relative to the transcriptional initiation site. Sp1 bound only to the −18 GC-rich sequence. Several sites of interaction were also evident in the distal region of the promoter. Both MAZ and Sp1 interacted with a sequence centered at −166, and MAZ bound weakly to an additional site centered at −130. Over expression of MAZ or Sp1 activated expression from the major late promoter in transient expression assays.