Washington University

Icahn School of Medicine at Mount Sinai

Beth Israel Deaconess

Beth Israel Deaconess Medical Center, Inc.

Herbert W Virgin

David Huabin Wang

Christiane Wobus

Guoyan Zhao

Larissa Thackray

Stephanie Karst

Adolfo Garcia-Sastre

Dan H Barouch

Peter Abbink

Rachel Presti

Joy Loh

Thad Stappenbeck

Christine Yokoyama

Natalia Frias-Staheli

Scott Handley

Nadia Vicki Giannakopoulos

The present invention relates to previously undescribed viruses that are associated with significant expansion of the virome, immunodeficiency, and enteropathy during lentiviral infection. The invention also provides methods to detect acquired immune deficiency syndrome (AIDS) or AIDS progression in a subject, methods to diagnose immunodeficiency or enteropathy in a subject, and methods to identify a therapeutic agent to treat the same.

Viruses associated with immunodeficiency and enteropathy and methods using same

Novel murine astroviruses, and methods of detecting the viruses are disclosed. Also disclosed are uses of the viruses and infected animals as model systems for discovery and development of vaccines and therapies for diseases caused by or associated with astrovirus infection, including human astrovirus-based diseases.

Methods of murine astrovirus detection

Viruses having an impaired ability to deISGylate ISG15 conjugates, in particular, viral mutants comprising a mutation in the viral genome that reduces or eliminates the ability of the viral OTU domain-containing protein encoded by the viral genome to deISGylate ISG15 conjugates and/or deubiquitinate ubiquitinated proteins and/or deNeddylate Neddylated proteins are disclosed. Such viral mutants may be used in the formulation of immunogenic compositions for inducing an immune response and preventing, managing and/or treating a viral infection. Also disclosed are methods for identifying anti-viral compounds, in particular, methods of identifying compounds that reduce or inhibit the deISGylation activity and/or deubiquitination and/or deNeddylation activity of a viral OTU domain-containing protein. The compounds identified using such methods may be used as antiviral agents for the prevention, treatment and/or management of viral infections.

Methods of preventing and treating viral infections by inhibiting the deISGylation activity of OTU domain-containing viral proteins

A norovirus-permissive cell culture infected with a norovirus, and methods of culturing a norovirus, are disclosed. Norovirus-permissive cells include dendritic cell-lineage cells, and macrophage-lineage cells, such as dendritic cells, and macrophages having a deficiency in a cellular anti-viral pathway such as a STAT-1-dependent pathway, an interferon receptor-dependent pathway, or a PKR-dependent pathway. Also disclosed are methods of screening anti-viral compounds against norovirus-permissive cells infected with norovirus, and norovirus adapted to grow in fibroblasts as well as macrophages that are not deficient in a cellular anti-viral pathway. Methods of making a norovirus vaccine are also disclosed. A replicative form of norovirus as well as its use in the development of an anti-viral agent and a polypeptide expression system are also described. Further disclosed are methods of detecting norovirus in a sample.

Norovirus detection, methods and compositions therefor

The invention disclosed herein relates to a newly discovered murine norovirus, and compositions and methods related thereto.

Murine calicivirus

The invention disclosed herein relates to a newly discovered murineand compositions and methods related thereto.

PCR-based method of detecting murine calicivirus

A norovirus-permissive cell culture infected with a norovirus, and methods of culturing a norovirus, are disclosed. Norovirus-permissive cells include dendritic cell-lineage cells, and macrophage-lineage cells, such as dendritic cells, and macrophages having a deficiency in a cellular anti-viral pathway such as a STAT-1-dependent pathway, an interferon receptor-dependent pathway, or a PKR-dependent pathway. Also disclosed are methods of screening anti-viral compounds against norovirus-permissive cells infected with norovirus, and norovirus adapted to grow in fibroblasts as well as macrophages that are not deficient in a cellular anti-viral pathway. Methods of making a norovirus vaccine are also disclosed.

Growing community of inventors

Clayton, MO, United States of America

Herbert W Virgin