A macrophage inflammatory protein homolog encoded by guinea pig cytomegalovirus signals via CC chemokine receptor 1.
Cytomegaloviruses encode homologs of cellular immune effector proteins, including chemokines (CKs) and CK receptor-like G protein-coupled receptors (GPCRs). Sequence of the guinea pig cytomegalovirus (GPCMV) genome identified an open reading frame (ORF) which predicted a 101 amino acid (aa) protein with homology to the macrophage inflammatory protein (MIP) subfamily of CC (beta) CKs, designated GPCMV-MIP. To assess functionality of this CK, recombinant GPCMV-MIP was expressed in HEK293 cells and assayed for its ability to bind to and functionally interact with a variety of GPCRs. Specific signaling was observed with the hCCR1 receptor, which could be blocked with hMIP -1alpha in competition experiments. Migration assays revealed that GPCMV-MIP was able to induce chemotaxis in hCCR1-L1.2 cells. Antisera raised against a GST-MIP fusion protein immunoprecipitated species of approximately 12 and 10 kDa from GPCMV-inoculated tissue culture lysates, and convalescent antiserum from GPCMV-infected animals was immunoreactive with GST-MIP by ELISA assay. These results represent the first substantive in vitro characterization of a functional CC CK encoded by a cytomegalovirus.
Penfold
Mark
M
ChemoCentryx, San Carlos, CA 94070, USA.
Miao
Zhenhua
Z
Wang
Yu
Y
Haggerty
Shannon
S
Schleiss
Mark R
MR
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002465:Cell Movement; D006168:Guinea Pigs; D019402:Macrophage Inflammatory Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000502:physiology*; D019211:Roseolovirus / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000502:physiology*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine; D014764:Viral Proteins; D002118:Calcium