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

Ren Huan Xu, Daniel Rubio, Felicia Roscoe, Tracy E. Krouse, Mary Ellen Truckenmiller, Christopher C. Norbury, Paul N. Hudson, Inger K. Damon, Antonio Alcamí, Luis J. Sigal

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

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.

Original languageEnglish (US)
Article numbere1002475
JournalPLoS pathogens
Volume8
Issue number1
DOIs
StatePublished - Jan 2012

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Fingerprint Dive into the research topics of 'Antibody inhibition of a viral type 1 interferon decoy receptor cures a viral disease by restoring interferon signaling in the liver'. Together they form a unique fingerprint.

Cite this