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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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XMRV: usage of receptors and potential co-receptors

Mohan Kumar Haleyur Giri Setty1, Krishnakumar Devadas, Viswanath Ragupathy

  • 1Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA. indira.hewlett@fda.hhs.gov

Virology Journal
|September 8, 2011
PubMed
Abstract

Insights

Xenotropic murine leukemia virus (XMRV) infects cells lacking the XPR1 receptor, suggesting alternative entry pathways. Chemokine receptors like CCR3 and Bonzo facilitate XMRV replication in hematopoietic cells.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Xenotropic murine leukemia virus (XMRV) is a gammaretrovirus linked to prostate cancer and chronic fatigue syndrome.
  • While XPR1 is a known XMRV receptor, its absence in some infected cells indicates other entry mechanisms.
  • This study investigates alternative receptors and co-receptors involved in XMRV cellular entry.

Purpose of the Study:

  • To explore the role of various receptors and co-receptors in XMRV infection.
  • To determine if chemokine receptors mediate XMRV entry into lymphoid and GHOST cells.
  • To identify specific receptors involved in XMRV replication.

Main Methods:

  • Infection of GHOST cells expressing CD4 and various chemokine receptors (CCR1-CCR8, Bonzo) with XMRV.
  • Infection of cell lines including LNCaP, DU145, and A549.
  • Quantification of XMRV replication using real-time quantitative PCR.

Main Results:

  • XMRV replicated in multiple cell lines, including A549 (lacking XPR1), with varying efficiency.
  • Significant XMRV replication was observed in GHOST cells expressing CD4 and specific chemokine receptors.
  • Higher replication occurred in CCR3 and Bonzo-expressing GHOST cells compared to others, though lower than in LNCaP, DU145, and A549 cells.

Conclusions:

  • XMRV can infect cells independently of XPR1 expression.
  • Chemokine receptors, particularly CCR3 and Bonzo, likely mediate XMRV entry into hematopoietic cells.
  • These findings suggest a broader range of cellular targets and entry mechanisms for XMRV.

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