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 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 Axthelm, Scott Wong

Research output: Contribution to journalArticle

14 Citations (Scopus)

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

Fingerprint

Complement Inactivating Agents
Monkeypox virus
Adaptive Immunity
Enzyme Inhibitors
Primates
complement
animal models
Monkeypox
loci
enzymes
Infection
infection
Democratic Republic of the Congo
Smallpox
Virulence Factors
Virus Diseases
virus replication
Macaca mulatta
Viruses
viruses

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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

In: Journal of Virology, Vol. 85, No. 18, 09.2011, p. 9527-9542.

Research output: Contribution to journalArticle

Estep, R, Messaoudi, I, O'Connor, MA, Li, H, Sprague, J, Barron, A, Engelmann, F, Yen, B, Powers, MF, Jones, JM, Robinson, BA, Orzechowska, BU, Manoharan, M, Legasse, A, Planer, S, Wilk, J, Axthelm, M & Wong, S 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, vol. 85, no. 18, pp. 9527-9542. https://doi.org/10.1128/JVI.00199-11
Estep, Ryan ; Messaoudi, Ilhem ; O'Connor, Megan A. ; Li, Helen ; Sprague, Jerald ; Barron, Alexander ; Engelmann, Flora ; Yen, Bonnie ; Powers, Michael F. ; Jones, John M. ; Robinson, Bridget A. ; Orzechowska, Beata U. ; Manoharan, Minsha ; Legasse, Alfred ; Planer, Shannon ; Wilk, Jennifer ; Axthelm, Michael ; Wong, Scott. / 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. In: Journal of Virology. 2011 ; Vol. 85, No. 18. pp. 9527-9542.
@article{7e150eaadd9d4164b1b45bd28e344c41,
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.",
author = "Ryan Estep and Ilhem Messaoudi and O'Connor, {Megan A.} and Helen Li and Jerald Sprague and Alexander Barron and Flora Engelmann and Bonnie Yen and Powers, {Michael F.} and Jones, {John M.} and Robinson, {Bridget A.} and Orzechowska, {Beata U.} and Minsha Manoharan and Alfred Legasse and Shannon Planer and Jennifer Wilk and Michael Axthelm and Scott Wong",
year = "2011",
month = "9",
doi = "10.1128/JVI.00199-11",
language = "English (US)",
volume = "85",
pages = "9527--9542",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "18",

}

TY - JOUR

T1 - 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

AU - Estep, Ryan

AU - Messaoudi, Ilhem

AU - O'Connor, Megan A.

AU - Li, Helen

AU - Sprague, Jerald

AU - Barron, Alexander

AU - Engelmann, Flora

AU - Yen, Bonnie

AU - Powers, Michael F.

AU - Jones, John M.

AU - Robinson, Bridget A.

AU - Orzechowska, Beata U.

AU - Manoharan, Minsha

AU - Legasse, Alfred

AU - Planer, Shannon

AU - Wilk, Jennifer

AU - Axthelm, Michael

AU - Wong, Scott

PY - 2011/9

Y1 - 2011/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=80052480937&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052480937&partnerID=8YFLogxK

U2 - 10.1128/JVI.00199-11

DO - 10.1128/JVI.00199-11

M3 - Article

C2 - 21752919

AN - SCOPUS:80052480937

VL - 85

SP - 9527

EP - 9542

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 18

ER -