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Title

Antibody inhibition of a viral type 1 interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver

AuthorsXu, Ren-Huan; Rubio, Daniel; Rosoce, Felicia; Krouse, Trayce E.; Truckenmiller, Mary Ellen; Norbury, Christopher C.; Hudson, Paul N.; Damon, Inger K.; Alcamí, Antonio ; Sigal, Luis J.
Issue Date2012
PublisherPublic Library of Science
CitationPLoS Pathogens 8 (1): e1002475 (2012)
AbstractType 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those that produce smallpox and mousepox, spread lympho-hematogenously. They also encode a decoy receptor for T1-IFN, the T1-IFN binding protein (T1-IFNbp), which is essential for virulence. We demonstrate that during mousepox, T1-IFNs protect the liver locally rather than systemically, and that the T1-IFNbp attaches to uninfected cells surrounding infected foci in the liver and the spleen to impair their ability to receive T1-IFN signaling, thus facilitating virus spread. Remarkably, this process can be reversed and mousepox cured late in infection by treating with antibodies that block the biological function of the T1-IFNbp. Thus, our findings provide insights on how T1-IFNs function and are evaded during a viral infection in vivo, and unveil a novel mechanism for antibody-mediated antiviral therapy.
URIhttp://hdl.handle.net/10261/115538
DOIhttp://dx.doi.org/10.1371/journal.ppat.1002475
Identifiersdoi: 10.1371/journal.ppat.1002475
issn: 1553-7366
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