title: 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.
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.
authors.affiliation: Vaccine and Gene Therapy Institute, Oregon Health & Science University, West Campus, 505 NW 185 Avenue, Beaverton, OR 97006, USA.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Estep
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
authors.forename: Megan A
authors.initials: MA
authors.lastname: O'Connor
authors.forename: Helen
authors.initials: H
authors.lastname: Li
authors.forename: Jerald
authors.initials: J
authors.lastname: Sprague
authors.forename: Alexander
authors.initials: A
authors.lastname: Barron
authors.forename: Flora
authors.initials: F
authors.lastname: Engelmann
authors.forename: Bonnie
authors.initials: B
authors.lastname: Yen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Powers
authors.forename: John M
authors.initials: JM
authors.lastname: Jones
authors.forename: Bridget A
authors.initials: BA
authors.lastname: Robinson
authors.forename: Beata U
authors.initials: BU
authors.lastname: Orzechowska
authors.forename: Minsha
authors.initials: M
authors.lastname: Manoharan
authors.forename: Alfred
authors.initials: A
authors.lastname: Legasse
authors.forename: Shannon
authors.initials: S
authors.lastname: Planer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wilk
authors.forename: Michael K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: Scott W
authors.initials: SW
authors.lastname: Wong
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001769:Blood / Q000821:virology; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D008168:Lung / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D045908:Mpox, Monkeypox / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008993:Monkeypox virus / Q000276:immunology* / Q000472:pathogenicity*; D018419:Primate Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology; D017422:Sequence Analysis, DNA; D012867:Skin / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins; D037521:Virulence Factors