Hypomorphic mutation in the site-1 protease Mbtps1 endows resistance to persistent viral infection in a cell-specific manner

Daniel L. Popkin, John R. Teijaro, Brian M. Sullivan, Shuzo Urata, Sophie Rutschmann, Juan Carlos De La Torre, Stefan Kunz, Bruce Beutler, Michael Oldstone

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV), which naturally persists in rodents, represents a model for HIV, HBV, and HCV. Cleavage of the viral glycoprotein precursor by membrane-bound transcription factor peptidase, site 1 (Mbtps1 or site-1 protease), is crucial for the life cycle of arenaviruses and therefore represents a potential target for therapy. Recently, we reported a viable hypomorphic allele of Mbtps1 (woodrat) encoding a protease with diminished enzymatic activity. Using the woodrat allele, we examine the role of Mbtps1 during persistent LCMV infection. Surprisingly, Mbtps1 inhibition limits persistent but not acute viral infection and is associated with an organ/cell type-specific decrease in viral titers. Analysis of bone marrow-derived dendritic cells from woodrat mice supports their specific role in resolving persistent viral infection. These results support in vivo targeting of Mbtps1 in the treatment of arenavirus infections and demonstrate a critical role for dendritic cells in persistent viral infections.

Original languageEnglish (US)
Pages (from-to)212-222
Number of pages11
JournalCell Host and Microbe
Volume9
Issue number3
DOIs
StatePublished - Mar 17 2011

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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    Popkin, D. L., Teijaro, J. R., Sullivan, B. M., Urata, S., Rutschmann, S., De La Torre, J. C., Kunz, S., Beutler, B., & Oldstone, M. (2011). Hypomorphic mutation in the site-1 protease Mbtps1 endows resistance to persistent viral infection in a cell-specific manner. Cell Host and Microbe, 9(3), 212-222. https://doi.org/10.1016/j.chom.2011.02.006