Deletion of the monkeypox virus inhibitor of complement enzymes locus impacts the adaptive immune response to monkeypox virus in a nonhuman primate model of infection

Ryan D. Estep, Ilhem Messaoudi, Megan A. O'Connor, Helen Li, Jerald Sprague, Alexander Barron, Flora Engelmann, Bonnie Yen, Michael F. Powers, John M. Jones, Bridget A. Robinson, Beata U. Orzechowska, Minsha Manoharan, Alfred Legasse, Shannon Planer, Jennifer Wilk, Michael K. Axthelm, Scott W. Wong

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Monkeypox virus (MPXV) is an orthopoxvirus closely related to variola virus, the causative agent of smallpox. Human MPXV infection results in a disease that is similar to smallpox and can also be fatal. Two clades of MPXV have been identified, with viruses of the central African clade displaying more pathogenic properties than those within the west African clade. The monkeypox inhibitor of complement enzymes (MOPICE), which is not expressed by viruses of the west African clade, has been hypothesized to be a main virulence factor responsible for increased pathogenic properties of central African strains of MPXV. To gain a better understanding of the role of MOPICE during MPXV-mediated disease, we compared the host adaptive immune response and disease severity following intrabronchial infection with MPXV-Zaire (n = 4), or a recombinant MPXV-Zaire (n = 4) lacking expression of MOPICE in rhesus macaques (RM). Data presented here demonstrate that infection of RM with MPXV leads to significant viral replication in the peripheral blood and lungs and results in the induction of a robust and sustained adaptive immune response against the virus. More importantly, we show that the loss of MOPICE expression results in enhanced viral replication in vivo, as well as a dampened adaptive immune response against MPXV. Taken together, these findings suggest that MOPICE modulates the anti-MPXV immune response and that this protein is not the sole virulence factor of the central African clade of MPXV.

Original languageEnglish (US)
Pages (from-to)9527-9542
Number of pages16
JournalJournal of virology
Volume85
Issue number18
DOIs
StatePublished - Sep 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Estep, R. D., Messaoudi, I., O'Connor, M. A., Li, H., Sprague, J., Barron, A., Engelmann, F., Yen, B., Powers, M. F., Jones, J. M., Robinson, B. A., Orzechowska, B. U., Manoharan, M., Legasse, A., Planer, S., Wilk, J., Axthelm, M. K., & Wong, S. W. (2011). Deletion of the monkeypox virus inhibitor of complement enzymes locus impacts the adaptive immune response to monkeypox virus in a nonhuman primate model of infection. Journal of virology, 85(18), 9527-9542. https://doi.org/10.1128/JVI.00199-11