Other

University of California

The J. David Gladstone Institutes

Mark A Goldsmith

Robert O Ralston

Stephen Chan

Robert E Atchison

Roberto F Speck

Yun You

Oliver Keppler

Methods and compositions are provided for at least slowing the progression of a filovirus mediated disease condition in a host. In the subject methods, an effective amount of an agent that at least reduces the amount of folate receptor mediated filovirus cell entry is administered to the host. The subject methods find use in both the prevention and treatment of filovirus associated disease conditions, including Marburg and Ebola-Zaire virus mediated disease conditions.

Methods and compositions for use in the treatment of filovirus mediated disease conditions

Cell fusion assays for identifying antiviral compounds are provided. In the cell fusion assays of the subject invention, a first cell that stably expresses on its surface an envelope protein of an enveloped virion and a second cell that stably expresses a receptor for the envelope protein on its surface are employed. The first and second cells each contain one component of a two component Tat reporter system that produces a detectable product in the presence of cell fusion. In practicing the subject screening methods, the first and second cells are first contacted with each other under cell fusion conditions in the presence of a candidate inhibitory agent. Next, the presence or absence of the detectable product is detected. Finally, the inhibitory activity of the candidate agent is derived from the presence or absence of the detectable product. Also provided are high throughput embodiments of the subject methods. In addition to the subject methods, systems and kits for performing the subject methods are provided.

Cell fusion assays for the identification of antiviral compounds, and systems and kits for practicing the same

The present invention features transgenic rodent models for HIV, wherein the transgenic rodent or transgenic rodent cell has incorporated into its genome genes encoding a human CD4 receptor and a human chemokine receptor. In particular the invention relates to transgenic rats, or mice characterized by being susceptible to infection with HIV, capable of expressing HIV structural genes, or HIV replication. The transgenic rodent or rodent cell of this invention is useful for studying the molecular basis of HIV infection, replication and pathogenicity, as well as for the testing of agents for new antiviral or vaccine strategies.

Transgenic rats and rat cell lines expressing human CD4 and a human chemokine receptor

Host cells may be treated for an infection or a hyperproliferative disorder which is characterized by the presence, in the affected cells, of a trans-acting factor capable of regulating gene expression by inserting into the cells a polynucleotide construct having a cis-acting regulatory sequence which is regulated by the trans-acting factor and an effector gene which renders said cell susceptible to protection or destruction. For example, the cis-acting region may be homologous to the HIV tar region, and the effector gene may encode ricin A or HSV-1 thymidine kinase. Upon infection with HIV, the HIV tat protein activates the tar region, and induces transcription and expression of ricin A, resulting in cell death, or of HSV-1 tk, resulting in cell death upon treatment with dideoxynucleoside agents such as acyclovir and gancyclovir.

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San Francisco, CA, United States of America

Mark A Goldsmith