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ACS Biomater Sci Eng. 2015 Nov 9;1(11):1050-1054. Epub 2015 Oct 20.

Tropism of CPMV to Professional Antigen Presenting Cells Enables a Platform to Eliminate Chronic Infections.

Author information

1
Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
2
Department of Dermatology, Case Western Reserve University Hospitals, Cleveland, Ohio 44106, United States.
3
Department of Biomedical Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States; Department of Radiology, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States; Department of Materials Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States; Department of Macromolecular Science and Engineering, Case Western Reserve University Schools of Medicine and Engineering, Cleveland, Ohio 44106, United States.
4
Department of Dermatology, Case Western Reserve University Hospitals, Cleveland, Ohio 44106, United States; Department of Pathology, Case Western Reserve University Hospitals, Cleveland, Ohio 44106, United States; Department of Molecular Biology and Microbiology, Case Western Reserve University Hospitals, Cleveland, Ohio 44106, United States.

Abstract

Chronic viral infections (e.g., HIV, HBV, HCV) represent a significant source of morbidity and mortality with over 500 million people infected worldwide. Dendritic cells (DCs) and macrophages are key cell types for productive viral replication and persistent systemic infection. We demonstrate that the plant virus cowpea mosaic virus (CPMV) displays tropism for such antigen presenting cells in both mice and humans, thus making it an ideal candidate for targeted drug delivery toward viral infections. Furthermore, we show inhibition of a key host protein for viral infection, site-1 protease (S1P), using the small molecule PF-429242 in the model pathogen arenavirus lymphocytic choriomeningitis virus (LCMV) limits viral growth. By packaging PF-429242 in CPMV, we are able to control drug release and efficiently deliver the drug. This sets the groundwork for utilizing the natural tropism of CPMV for a therapeutic approach that specifically targets cell types most commonly subverted by chronic viruses.

KEYWORDS:

PF-429242; cowpea mosaic virus; lymphocytic choriomeningitis virus; nanoparticles; site-1 protease; tropism

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