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Integrin alphavbeta3 is a coreceptor for human cytomegalovirus

Xin Wang1, David Y Huang, Shu-Mei Huong

  • 1Lineberger Comprehensive Cancer Center, CB#7295, Lineberger Building, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.

Nature Medicine
|April 19, 2005
PubMed

Insights

Human cytomegalovirus (HCMV) uses both epidermal growth factor receptor (EGFR) and integrin alphavbeta3 as coreceptors for infection. Their coordinated signaling is crucial for viral entry and early infection events.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Human cytomegalovirus (HCMV) is a significant opportunistic pathogen causing birth defects and severe illness in immunocompromised individuals.
  • HCMV's broad tropism indicates the involvement of multiple cellular receptors for infection.
  • Previous research identified the epidermal growth factor receptor (EGFR) as an HCMV receptor.

Purpose of the Study:

  • To investigate additional cellular receptors utilized by HCMV for entry and infection.
  • To elucidate the role of integrin alphavbeta3 in HCMV pathogenesis.
  • To understand the coordinated function of EGFR and integrin alphavbeta3 in HCMV infection.

Main Methods:

  • Investigated HCMV interaction with cellular receptors using cell-based assays.
  • Analyzed the binding of HCMV glycoproteins (gB and gH) to EGFR and integrin alphavbeta3.
  • Examined the translocation of integrin alphavbeta3 to lipid rafts and its interaction with EGFR.
  • Assessed the impact of EGFR and alphavbeta3 coordination on early HCMV infection events.

Main Results:

  • HCMV utilizes integrin alphavbeta3 as a coreceptor in addition to EGFR.
  • HCMV glycoproteins gB and gH bind independently to EGFR and alphavbeta3, respectively, initiating entry.
  • Integrin alphavbeta3 translocates to lipid rafts, interacting with EGFR to induce coordinated signaling.
  • This EGFR-alphavbeta3 signaling coordination is essential for viral entry, RhoA downregulation, stress-fiber disassembly, and nuclear trafficking.

Conclusions:

  • EGFR and integrin alphavbeta3 function as essential coreceptors for HCMV entry and signaling.
  • The coordinated action of these coreceptors is critical for early stages of HCMV infection.
  • This discovery provides a fundamental basis for understanding HCMV pathogenesis and developing targeted therapies.

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