Arenavirus receptor and methods of use

摘要

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.