A macrophage inflammatory protein homolog encoded by guinea pig cytomegalovirus signals via CC chemokine receptor 1

Mark Penfold, Zhenhua Miao, Yu Wang, Shannon Haggerty, Mark R. Schleiss

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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 (β) 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 -1α 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 ~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.

Original languageEnglish (US)
Pages (from-to)202-212
Number of pages11
JournalVirology
Volume316
Issue number2
DOIs
StatePublished - Nov 25 2003

Bibliographical note

Funding Information:
The authors acknowledge helpful discussions with Christopher Karp and Yasmine Belkaid, Molecular Immunology Division, Children's Hospital Research Foundation. The technical assistance of Greg Stroup is acknowledged. This work was supported by National Institute of Health HD044864-01 and HD38416-01, and March of Dimes Basic Research Grants 6-FY98/99-0416 and FY01-226.

Keywords

  • Guinea pig cytomegalovirus
  • Immune evasion
  • Viral chemokine

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