Abstract: The present invention relates to recombinant rhesus cytomegalovirus (RhCMV) and human cytomegalovirus (HCMV) vectors encoding heterologous antigens, such as pathogen-specific antigens or tumor antigens, which may be used, for example, for the treatment or prevention of infectious disease or cancer. The recombinant RhCMV or HCMV vectors elicit and maintain high level cellular immune responses specific for the heterologous antigen while including deletions in one or more genes essential or augmenting for CMV replication, dissemination or spread.

Abstract: Disclosed herein are CMV vectors that include a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), an active UL128 protein (or an ortholog thereof), but wherein the CMV vector lacks an active UL130 protein (or an ortholog thereof). Also disclosed herein are CMV vectors comprising: a heterologous protein antigen, an active UL131 protein (or an ortholog thereof), an active UL130 protein (or an ortholog thereof), but wherein the CMV vector lacks an active UL128 protein. Further disclosed are methods of using CMV vectors to generate an immune response characterized as having at least 10% of the CD8+ T cells directed against epitopes presented by MHC Class II.

Abstract: Disclosed herein is a viral polypeptide and homologs thereof that inhibit an immune response, particularly the response of memory and effector CD4+ and CD8+ T cells.

Abstract: This invention also relates to recombinant vectors expressing one or more of the human CMV (HCMV) glycoproteins US2, US3, US6 and US11 or corresponding functional rhesus CMV (RhCMV) homologues Rh182, Rh184, Rh185 or Rh189, methods of making them, uses for them, expression products from them, and uses for the expression products. This invention also relates to recombinant cytomegalovirus vectors vectors lacking one or more of the glycoproteins, methods of making them, uses for them, expression products from them, and uses for the expression products.

Abstract: Pharmaceutical compositions that comprise an siRNA molecule used in the treatment of diseases caused by flavivirus infection and methods of their use are disclosed. The pharmaceutical compositions treat diseases caused by yellow fever virus, West Nile virus, and dengue virus and include a single pharmaceutical composition active against all four dengue virus serotypes.

Abstract: Disclosed herein are recombinant CMV vectors which may comprise a heterologous antigen that can repeatedly infect an organism while inducing a CD8+ T cell response to immunodominant epitopes of the heterologous antigen. The CMV vector may comprise a deleterious mutation in the US 11 glycoprotein or a homolog thereof.

Abstract: Disclosed herein are expression vectors that encode cowpox virus protein CPXV014 and homologs thereof that are useful in inhibiting CD3/CD28 mediated T cell stimulation. Further disclosed are polypeptide compositions comprising CPXV014 and homologs thereof as well as methods of inhibiting CD3/CD28 mediated T cell stimulation using the polypeptide compositions.

Abstract: Aspects of the present invention use gene expression profiling, and gene silencing methods to identify and provide a plurality of ‘validated’ KSHV-induced cellular gene sequences and pathways useful as targets for modulation of KSHV-mediated effects on cellular proliferation and phenotype (e.g., cancer) associated with latent and lytic phases of the Kaposi's sarcoma-associated herpesvirus (KSHV; Human herpesvirus 8; HHV8) life cycle. Particular embodiments provide therapeutic compositions, and methods for modulation and treatment of KSHV infection or KSHV-mediated effects on cellular proliferation and phenotype, comprising inhibition of KSHV-induced gene sequences or products thereof. Additional embodiments provide screening assays for compounds useful to modulate KSHV infection or KSHV-mediated effects on cellular proliferation and phenotype. Further embodiments provide diagnostic and/or prognostic assays for KSHV infection or related conditions.

Abstract: The present invention utilizes nucleic acid microarray technology to identify changes in the host endothelial cell transcription pattern that occurs during the latent and lytic phase of the KSHV life cycle. The production or activity of some genes up regulated during the lytic cycle were subsequently inhibited, and two such targets were shown to have a role in expression of late viral genes. Using this combined approach we have identified cellular pathways previously unknown to be important for KSHV infection, and present evidence for the efficiency of the novel antiviral approaches thus discovered. In addition, the present invention identifies a wide variety of endothelial cells genes and pathways that are involved in a variety of endothelial cell-mediated activity, including angiogenesis and transformation.

Abstract: The present invention utilizes nucleic acid microarray technology to identify changes in the host endothelial cell transcription pattern that occurs during the latent and lytic phase of the KSHV life cycle. The production or activity of some genes up regulated during the lytic cycle were subsequently inhibited, and two such targets were shown to have a role in expression of late viral genes. Using this combined approach we have identified cellular pathways previously unknown to be important for KSHV infection, and present evidence for the efficiency of the novel antiviral approaches thus discovered. In addition, the present invention identifies a wide variety of endothelial cells genes and pathways that are involved in a variety of endothelial cell-mediated activity, including angiogenesis and transformation.

Abstract: The human cytomegalovirus (HCMV) genomic US region encodes a family of homologous genes essential for the inhibition of major histocompatiblity complex (MHC) class I mediated antigen presentation observed during viral infection. Here we show that US3 and US6 encode ER-resident glycoproteins that prevent intracellular transport of NMC class I molecules by different mechanisms. US3 retains stable MHC class I heterodimers in the ER which are loaded with peptides while retained in the ER. US6 prevents MHC class I assembly with .beta.2 microglobulin which results in free heavy chains leaving the ER. These genes have the potential to prevent unwanted immunological reactivities triggered by MHC class I molecules.