Abstract
Human cytomegaloviruses (HCMVs) are important pathogens in immunocompromised patients and newborns. The viral chemokine, vCXCL-1, of the Toledo (Tol) strain of HCMV has been implicated in HCMV virulence. Chimpanzee CMV (CCMV) has several genes with similarity to the vCXCL-1(Tol) gene, UL146. In order to test whether the CCMV viral chemokine, vCXCL-1(CCMV), is similar to vCXCL-1(Tol), we characterized its function in vitro. Receptor binding, activation, chemotaxis, signaling, and apoptosis in neutrophils were compared between vCXCL-1(Tol) and vCXCL-1(CCMV) and host chemokines. Although the homologues had similar activation potentials, chemotactic properties, and signaling, vCXCL-1(CCMV) had a approximately 70-fold lower affinity for CXCR2 and displayed differences in integrin upregulation and neutrophil apoptosis. These data demonstrate that in spite of extensive amino acid variability in vCXCL-1, CCMV may provide a model for assessing the role of vCXCL-1 in CMV pathogenesis in vivo.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis
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Baculoviridae / genetics
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CD11b Antigen / metabolism
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CD11c Antigen / metabolism
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Calcium Signaling
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Chemokines, CXC / chemistry
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Chemokines, CXC / genetics*
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Chemokines, CXC / physiology*
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Conserved Sequence
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Cytomegalovirus / genetics*
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Cytomegalovirus / immunology*
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Cytomegalovirus / pathogenicity
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Humans
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In Vitro Techniques
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Molecular Sequence Data
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Neutrophils / immunology
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Neutrophils / pathology
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Neutrophils / virology
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Pan troglodytes / immunology
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Pan troglodytes / virology*
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Protein Sorting Signals / genetics
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Receptors, Interleukin-8B / physiology
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Sequence Homology, Amino Acid
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Viral Proteins / chemistry
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Viral Proteins / genetics*
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Viral Proteins / immunology
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Viral Proteins / physiology*
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Virulence / genetics
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Virulence / immunology
Substances
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CD11b Antigen
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CD11c Antigen
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Chemokines, CXC
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ITGAM protein, human
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Protein Sorting Signals
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Receptors, Interleukin-8B
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Viral Proteins