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

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...

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Veröffentlicht in:Cytokine (Philadelphia, Pa.) Pa.), 2008-08, Vol.43 (2), p.220-228
Hauptverfasser: Jones, John M., Messauodi, Ilhem, Estep, Ryan D., Orzechowska, Beata, Wong, Scott W.
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container_issue 2
container_start_page 220
container_title Cytokine (Philadelphia, Pa.)
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creator Jones, John M.
Messauodi, Ilhem
Estep, Ryan D.
Orzechowska, Beata
Wong, Scott W.
description 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.
doi_str_mv 10.1016/j.cyto.2008.05.016
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subjects Amino Acid Sequence
Animals
Cell Line
Chemokine inhibitor
Chemokines
Chemotaxis
Encephalomyelitis, Autoimmune, Experimental - metabolism
Humans
Lipopolysaccharide Receptors - metabolism
Macaca mulatta
Macrophage Inflammatory Proteins - antagonists & inhibitors
Macrophage Inflammatory Proteins - metabolism
Molecular Sequence Data
Monkeypox virus
Monkeypox virus - metabolism
Multiple sclerosis
Orthopoxvirus
Poxviruses
Protein Binding
Sequence Alignment
Sequence Homology, Amino Acid
Variola
Viral Proteins - chemistry
Viral Proteins - metabolism
Viral Proteins - pharmacology
title Monkeypox virus viral chemokine inhibitor (MPV vCCI), a potent inhibitor of rhesus macrophage inflammatory protein-1
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