Machupo virus expressing GPC of the Candid#1 vaccine strain of Junin virus is highly attenuated and immunogenic

Takaaki Koma, Michael Patterson, Cheng Huang, Alexey V. Seregin, Payal D. Maharaj, Milagros Miller, Jeanon N. Smith, Aida G. Walker, Steven Hallam, Slobodan Paessler

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Abstract

Machupo virus (MACV) is the causative agent of Bolivian hemorrhagic fever. Our previous study demonstrated that a MACV strain with a single amino acid substitution (F438I) in the transmembrane domain of glycoprotein is attenuated but genetically unstable in mice. MACV is closely related to Junin virus (JUNV), the causative agent of Argentine hemorrhagic fever. Others and our group have identified the glycoprotein to be the major viral factor determining JUNV attenuation. In this study, we tested the compatibility of the glycoprotein of the Candid#1 live-attenuated vaccine strain of JUNV in MACV replication and its ability to attenuate MACV in vivo. Recombinant MACV with the Candid#1 glycoprotein (rMACV/Cd#1-GPC) exhibited growth properties similar to those of Candid#1 and was genetically stable in vitro. In a mouse model of lethal infection, rMACV/Cd#1-GPC was fully attenuated, more immunogenic than Candid#1, and fully protective against MACV infection. Therefore, the MACV strain expressing the glycoprotein of Candid#1 is safe, genetically stable, and highly protective against MACV infection in a mouse model.

Original languageEnglish (US)
Pages (from-to)1290-1297
Number of pages8
JournalJournal of Virology
Volume90
Issue number3
DOIs
StatePublished - 2016

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ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Koma, T., Patterson, M., Huang, C., Seregin, A. V., Maharaj, P. D., Miller, M., Smith, J. N., Walker, A. G., Hallam, S., & Paessler, S. (2016). Machupo virus expressing GPC of the Candid#1 vaccine strain of Junin virus is highly attenuated and immunogenic. Journal of Virology, 90(3), 1290-1297. https://doi.org/10.1128/JVI.02615-15