We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Antibody Inhibition of a Viral Type 1 Interferon Decoy Receptor Cures a Viral Disease by Restoring Interferon Signaling in the Liver.
- Authors
Ren-Huan Xu; Rubio, Daniel; Roscoe, Felicia; Krouse, Tracy E.; Truckenmiller, Mary Ellen; Norbury, Christopher C.; Hudson, Paul N.; Damon, Inger K.; Alcamí, Antonio; Sigal, Luis J.
- Abstract
Type 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.
- Publication
PLoS Pathogens, 2012, Vol 8, Issue 1, p1
- ISSN
1553-7366
- Publication type
Academic Journal
- DOI
10.1371/journal.ppat.1002475