Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action

Victor Van Berkel, John Barrett, H. Lee Tiffany, Daved H. Fremont, Philip M. Murphy, Douglas McFadden, Samuel H. Speck, Herbert W. Virgin IV

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Chemokines are involved in recruitment and activation of hematopoietic cells at sites of infection and inflammation. The M3 gene of γHV68, a gamma- 2 herpesvirus that infects and establishes a lifelong latent infection and chronic vasculitis in mice, encodes an abundant secreted protein during productive infection. The M3 gene is located in a region of the genome that is transcribed during latency. We report here that the M3 protein is a high- affinity broad-spectrum chemokine scavenger. The M3 protein bound the CC chemokines human regulated upon activation of normal T-cell expressed and secreted (RANTES), murine macrophage inflammatory protein 1α (MIP-1α), and murine monocyte chemoattractant protein 1 (MCP-1), as well as the human CXC chemokine interleukin-8, the murine C chemokine lymphotactin, and the murine CX3C chemokine fractalkine with high affinity (K(a) = 1.6 to 18.7 nM). M3 protein chemokine binding was selective, since the protein did not bind seven other CXC chemokines (K(d) > 1 μM). Furthermore, the M3 protein abolished calcium signaling in response to murine MIP-1α and murine MCP-1 and not to murine KC or human stromal cell-derived factor 1 (SDF-1), consistent with the binding data. The M3 protein was also capable of blocking the function of human CC and CXC chemokines, indicating the potential for therapeutic applications. Since the M3 protein lacks homology to known chemokines, chemokine receptors, or chemokine binding proteins, these studies suggest a novel herpesvirus mechanism of immune evasion.

Original languageEnglish (US)
Pages (from-to)6741-6747
Number of pages7
JournalJournal of Virology
Volume74
Issue number15
DOIs
StatePublished - Aug 1 2000
Externally publishedYes

Fingerprint

chemokines
Chemokines
binding proteins
Carrier Proteins
CXC Chemokines
mice
Proteins
proteins
Macrophage Inflammatory Proteins
CC Chemokines
Chemokine CCL2
Herpesviridae
CX3C Chemokines
C Chemokines
Infection
Chemokine CX3CL1
Immune Evasion
Chemokine CXCL12
infection
immune evasion

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Van Berkel, V., Barrett, J., Tiffany, H. L., Fremont, D. H., Murphy, P. M., McFadden, D., ... Virgin IV, H. W. (2000). Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action. Journal of Virology, 74(15), 6741-6747. https://doi.org/10.1128/JVI.74.15.6741-6747.2000

Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action. / Van Berkel, Victor; Barrett, John; Tiffany, H. Lee; Fremont, Daved H.; Murphy, Philip M.; McFadden, Douglas; Speck, Samuel H.; Virgin IV, Herbert W.

In: Journal of Virology, Vol. 74, No. 15, 01.08.2000, p. 6741-6747.

Research output: Contribution to journalArticle

Van Berkel, V, Barrett, J, Tiffany, HL, Fremont, DH, Murphy, PM, McFadden, D, Speck, SH & Virgin IV, HW 2000, 'Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action', Journal of Virology, vol. 74, no. 15, pp. 6741-6747. https://doi.org/10.1128/JVI.74.15.6741-6747.2000
Van Berkel, Victor ; Barrett, John ; Tiffany, H. Lee ; Fremont, Daved H. ; Murphy, Philip M. ; McFadden, Douglas ; Speck, Samuel H. ; Virgin IV, Herbert W. / Identification of a gammaherpesvirus selective chemokine binding protein that inhibits chemokine action. In: Journal of Virology. 2000 ; Vol. 74, No. 15. pp. 6741-6747.
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