Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis

David Maussang, Dennis Verzijl, Marijke Van Walsum, Rob Leurs, Jens Holl, Olivier Pleskoff, Detlef Michel, Guus A.M.S. Van Dongen, Martine J. Smit*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)13068-13073
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number35
Publication statusPublished - 29 Aug 2006

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