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Journal of Virology, August 2005, p. 10330-10338, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10330-10338.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Cytomegalovirus UL131 Open Reading Frame Is Required for Epithelial Cell Tropism

Dai Wang and Thomas Shenk*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544

Received 10 February 2005/ Accepted 24 May 2005

Epithelial cells are one of the prominent cell types infected by human cytomegalovirus (HCMV) within its host. However, many cultured epithelial cells, such as ARPE-19 retinal pigmented epithelial cells, are poorly infected by laboratory-adapted strains in cell culture, and little is known about the viral factors that determine HCMV epithelial cell tropism. In this report, we demonstrate that the UL131 open reading frame (ORF), and likely the entire UL131-128 locus, is required for efficient infection of epithelial cells. Repair of the mutated UL131 gene in the AD169 laboratory strain of HCMV restored its ability to infect both epithelial and endothelial cells while compromising its ability to replicate in fibroblasts. ARPE-19 epithelial cells support replication of the repaired AD169 virus as well as clinical isolates of HCMV. Productive infection of cultured epithelial cells, endothelial cells, and fibroblasts with the repaired AD169 virus leads to extensive membrane fusion and syncytium formation, suggesting that the virus may spread through cell-cell fusion.

* Corresponding author. Mailing address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014. Phone: (609) 258-5992. Fax: (609) 258-1704. E-mail: tshenk{at}molbio.princeton.edu.

Journal of Virology, August 2005, p. 10330-10338, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10330-10338.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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