University of California

The Scripps Research Institute

University of Iowa Research Foundation

Michael Oldstone

Kevin P Campbell

Robert M Krug

Michael D Henry

Ethan Bier

Roger Williamson

John R Teijaro

Hiroki Yamada

Wei Cao

Margery Smelkinson

Meghana Malur

Method and composition for protection and treatment against influenza viral infection by modulating the activity of at least one essential host signaling pathways, including the Hedgehog (Hh), the Bone Morphogenetic Protein (BMP), the Notch (N) signaling pathways or combinations thereof, which activity is altered by the viral protein NS1. The method and composition comprise use of a compound that modulates at least one of these essential host signaling pathways for preventing or controlling symptoms associated with influenza viral infection. The method or composition can also be used either alone or in combination with other therapeutic agents for treating or protecting against influenza infection, and associated syndromes.

Protection and treatment against influenza infection

Disclosed is a method for inhibiting the binding of an arenavirus to a cellular receptor. The method involves providing, in soluble form, a reagent comprising .alpha.-dystroglycan or a portion thereof, the reagent being characterized by the ability to bind to the arenavirus thereby inhibiting the binding of the arenavirus to the cellular receptor. The reagent is contacted with an arenavirus particle prior to infection of a cell by the arenavirus particle. Also disclosed are methods for treating an arenavirus infection in a patient and preventing an arenavirus infection in an individual at risk. These methods involve providing a therapeutic composition comprising .alpha.-dystroglycan or a portion thereof which is characterized by the ability to bind to arenaviruses, thereby inhibiting the binding of arenaviruses to a cellular receptor; and administering the composition to the patient or individual at risk. Arenaviruses to which the methods of the present invention apply include, without limitation, Lymphocyte Choriomeningitis Virus, Lassa fever virus, Mobala, and Oliveros. In another aspect, the disclosure relates to an embryonic stem cell line, and cells derived therefrom, which is homozygous for a disrupted dystroglycan gene, wherein the disruption prevents the synthesis of functional dystroglycan in the cells. Applications of the dystroglycan null embryonic stem cells include producing dystroglycan or a portion thereof in the cells and also for identifying portions of dystroglycan necessary for arenavirus infection. Also disclosed is a method for identifying antiviral compounds which interfere specifically with the binding of arenavirus and .alpha.-dystroglycan, comprising providing a binding assay system for the determination of binding of arenavirus and .alpha.-dystroglycan. The candidate antiviral compounds are introduced into the binding assay system and antiviral compounds which substantially inhibit binding of arenavirus to .alpha.-dystroglycan are identified.

Arenavirus receptor and methods of use

Growing community of inventors

La Jolla, CA, United States of America

Michael Oldstone