Princeton University

Affymetrix, Inc.

Barnes Jewish Hospital

Thomas E Shenk

Joshua D Rabinowitz

Dai Wang

Ileana M Cristea

Richard Jude Samulski

Todd M Greco

Long-Sheng Chang

Arnold J Levine

Emre Koyuncu

Josh Munger

Bryson Bennett

Robert J Schneider

Cathy A Finlay

Rommel A Mathias

Nicole Gudleski O'Regan

Adam Oberstein

Thomas R Gingeras

Thomas F Deuel

Hua Zhu

Mark A Labow

Steven B Baim

Zhao-Yi Wang

Sean Liu

The present application provides a method of assaying pyruvate dehydrogenase complex (PDHC) activity in a mammalian cell that expresses human sirtuin 4 (SIRT4) comprising measuring a level of a dihydrolipoyllysine acetyltransferase (DLAT) lipoamide peptide comprising the amino acid sequence TDK[lipoyl]AT in the cell. The present application also demonstrates that sirtuin 4 (SIRT4) acts as a cellular lipoamidase that negatively regulates pyruvate dehydrogenase complex (PDHC) activity through hydrolysis of its lipoamide cofactors.

Sirtuin 4 (SIRT4) lipoamidase activity and uses thereof

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.

Cytomegalovirus surface protein complex for use in vaccines and as a drug target

A method for enhancing infectivity of HCMV virus particles is provided.

Method to increase the infectivity of virus particles

Agents and methods of inhibiting or improving the growth of viruses are provided.

Sirtuin modulators as inhibitors of cytomegalovirus

The present application demonstrates that sirtuin 4 (SIRT4) acts as a cellular lipoamidase that negatively regulates pyruvate dehydrogenase complex (PDHC) activity through hydrolysis of its lipoamide cofactors.

SIRT4 lipoamidase activity and uses thereof

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.

Cytomegalovirus vaccines and methods of production

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.

Treatment of viral infections by modulation of host cell metabolic pathways

A method for improving virus production in a host cell infected with the virus is provided.

Method to produce virus in cultured cells

The present invention provides methods and compounds for treating viral infections using modulators of host cell enzymes relating to long chain fatty acid and lipid droplet metabolism. It includes a method of treating viral infections using triacsin C and its relatives, analogs and derivatives as well as other inhibitors of long chain fatty acid metabolism and lipid droplet metabolism.

Inhibitors of long and very long chain fatty acid metabolism as broad spectrum anti-virals

A method of treating or preventing a viral infection in a mammal by administering a compound or pharmaceutically acceptable derivative thereof that inhibits a phosphatidic acid synthesis enzyme.

Inhibition of glycerol-3-phosphate acyltransferase (GPAT) and associated enzymes for treatment of viral infections

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) 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, and in animal models. Animal models are then used to test efficacy of candidate compounds in preventing and treating viral infections. Antiviral activity of enzyme inhibitors is demonstrated.

Growing community of inventors

Princeton, NJ, United States of America

Thomas E Shenk