Nature Medicine11, 515 - 521 (2005)
Published online: 17 April 2005; | doi:10.1038/nm1236
Integrin v3 is a coreceptor for human cytomegalovirus
Xin Wang1, David Y Huang2, Shu-Mei Huong1
& Eng-Shang Huang1, 3
1
Lineberger Comprehensive Cancer Center, CB#7295, Lineberger Building, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
2
Department of Neurology, Bioinformatics Building, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
3
Department of Medicine and Department of Microbiology and Immunology, Bioinformatics Building, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Human cytomegalovirus (HCMV) is a widespread opportunistic pathogen that causes birth defects in newborns and severe disease in immunocompromised individuals. The broad tropism of HCMV infection suggests that it uses multiple receptors. We recently showed that the epidermal growth factor receptor (EGFR) serves as a receptor for HCMV. Here we show that HCMV also uses integrin v3 as a coreceptor. Upon infection, HCMV glycoproteins gB and gH independently bind to EGFR and v3, respectively, to initiate viral entry and signaling. v3 then translocates to lipid rafts where it interacts with EGFR to induce coordinated signaling. The coordination between EGFR and v3 is essential for the early events of HCMV infection, including viral entry, RhoA downregulation, stress-fiber disassembly and viral nuclear trafficking. Our findings support a model in which EGFR and v3 work together as coreceptors for HCMV entry and signaling. This discovery is fundamental to understanding HCMV pathogenesis and developing treatment strategies targeted to viral receptors.
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v
3 is a coreceptor for human cytomegalovirus
v
3 as a coreceptor. Upon infection, HCMV glycoproteins gB and gH independently bind to EGFR and 
