2. Academic Validation
  3. Site-1 protease mediated GPC processing is required for persistence of LCMV Clone 13

Site-1 protease mediated GPC processing is required for persistence of LCMV Clone 13

  • Npj Viruses. 2026 Mar 14;4(1):18. doi: 10.1038/s44298-026-00184-7.
Ruifeng Zhou 1,  Haydar Witwit 1,  Tingting Ai 1,  Maheeka Bimal 1,  Rachel Y Sattler 1,  Kristi L Marquardt 1,  Beatrice Cubitt 1,  Arthur S Kim 1 2,  John R Teijaro 3,  Juan Carlos de la Torre 4
Affiliations

Affiliations

  • 1 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • 2 Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
  • 3 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. [email protected].
  • 4 Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. [email protected].
PMID: 41826412 DOI: 10.1038/s44298-026-00184-7
Abstract

Most enveloped viruses rely on Furin for maturation of their surface glycoprotein. In contrast, mammarenaviruses process their glycoprotein precursor (GPC) using host site-1 protease (S1P), yet the biological implications of this unique reliance on S1P remain unclear. Here, we characterized a furin-dependent recombinant form (rCl13-RRRR) of the persistent clone 13 variant of LCMV (rCl13). Although rCl13-RRRR exhibited fitness comparable to rCl13 in cultured cells, it was highly attenuated in vivo and failed to establish persistence in immunocompetent mice. Clearance of rCl13-RRRR required interferon and CD8+ T cells, and immunization with rCl13-RRRR conferred protective immunity against a subsequent lethal LCMV challenge. Our results demonstrate that S1P-mediated processing of GPC is a key determinant of mammarenavirus fitness and immune evasion in vivo and highlight S1P as a promising and druggable target for host-directed Antiviral strategies against human pathogenic mammarenaviruses.

Figures
Products