Monkeypox virus viral chemokine inhibitor (MPV vCCI), a potent inhibitor of rhesus macrophage inflammatory protein-1

John M. Jones, Ilhem Messauodi, Ryan Estep, Beata Orzechowska, Scott Wong

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Monkeypox virus (MPV) is an orthopoxvirus with considerable homology to variola major, the etiologic agent of smallpox. Although smallpox was eradicated in 1976, the outbreak of MPV in the U.S. highlights the health hazards associated with zoonotic infections. Like other orthopoxviruses, MPV encodes a secreted chemokine binding protein, vCCI that is abundantly expressed and secreted from MPV infected cells. EMSA data shows vCCI efficiently binds rhesus MIP-1α (rhMIP-1α) at near one to one stoichiometry. In vitro chemotaxis experiments demonstrate that vCCI completely inhibits rhMIP-1α mediated chemotaxis, while in vivo recruitment assays in rhesus macaques using chemokine-saturated implants show a decrease in the number of CD14+ cells responding to rhMIP-1α when vCCI is present, suggesting vCCI is effectively inhibiting chemokine function both in vitro and in vivo. More importantly, we demonstrate that vCCI can diminish the severity of the acute phase and completely inhibit the relapsing phase of experimental allergic encephalomyelitis (EAE) disease. These data represent the first in vitro and in vivo characterization of vCCI emphasizing its function as a potent inhibitor of rhMIP-1α. Furthermore, the ability of vCCI to inhibit relapsing EAE disease represents a novel therapeutic approach for treating chemokine-mediated diseases.

Original languageEnglish (US)
Pages (from-to)220-228
Number of pages9
JournalCytokine
Volume43
Issue number2
DOIs
StatePublished - Aug 2008

Fingerprint

Monkeypox virus
Macrophage Inflammatory Proteins
Viruses
Chemokines
Smallpox
Orthopoxvirus
Autoimmune Experimental Encephalomyelitis
Chemotaxis
Health hazards
Aptitude
Zoonoses
Macaca mulatta
Stoichiometry
Disease Outbreaks
Assays
Carrier Proteins
Cell Count
Health
In Vitro Techniques
Experiments

Keywords

  • Chemokine inhibitor
  • Chemokines
  • Chemotaxis
  • Multiple sclerosis
  • Poxviruses

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

Cite this

Monkeypox virus viral chemokine inhibitor (MPV vCCI), a potent inhibitor of rhesus macrophage inflammatory protein-1. / Jones, John M.; Messauodi, Ilhem; Estep, Ryan; Orzechowska, Beata; Wong, Scott.

In: Cytokine, Vol. 43, No. 2, 08.2008, p. 220-228.

Research output: Contribution to journalArticle

Jones, John M. ; Messauodi, Ilhem ; Estep, Ryan ; Orzechowska, Beata ; Wong, Scott. / Monkeypox virus viral chemokine inhibitor (MPV vCCI), a potent inhibitor of rhesus macrophage inflammatory protein-1. In: Cytokine. 2008 ; Vol. 43, No. 2. pp. 220-228.
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