Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis

D.A.B. Maussang Detaille, D. Verzijl, M Stigter-van Walsum, R. Leurs, J. Holl, O.C. Pleskoff, D. Michel, A.A.M.S. van Dongen, M.J. Smit, David Maussang

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174 Citations (Scopus)

Abstract

Human cytomegalovirus (HCMV) is a widely spread herpesvirus, suggested to play a role in tumor progression. US28, a chemokine receptor encoded by HCMV, binds a broad spectrum of chemokines and constitutively activates various pathways linked to proliferation. Our studies reveal that expression of US28 induces a proangiogenic and transformed phenotype by up-regulating the expression of vascular endothelial growth factor and enhancing cell growth and cell cycle progression. US28-expressing cells promote tumorigenesis when injected into nude mice. The G protein-uncoupled constitutively inactive mutant of US28, induces delayed and attenuated tumor formation, indicating the importance of constitutive receptor activity in the early onset of tumor development. Importantly, also in glioblastoma cells infected with the newly isolated clinical HCMV strain Titan, US28 was shown to be involved in the HCMV-induced angiogenic phenotype. Hence, the constitutively activated chemokine receptor US28 might act as a viral oncogene and enhance and/or promote HCMV-associated tumor progression. © 2006 by The National Academy of Sciences of the USA.
Original languageEnglish
Pages (from-to)13068-73
Number of pages6
JournalPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume103
Issue number35
DOIs
Publication statusPublished - 29 Aug 2006

Keywords

  • Cancer
  • Drug target
  • G protein-coupled receptor
  • VEGF
  • Viral infection

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