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Journal of Virology, March 2008, p. 2170-2181, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.02316-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Functional Genetic Analysis of Rhesus Cytomegalovirus: Rh01 Is an Epithelial Cell Tropism Factor{triangledown}

Anders E. Lilja,1* W. L. William Chang,2 Peter A. Barry,2,3 S. Patricia Becerra,4 and Thomas E. Shenk1

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544,1 Center for Comparative Medicine,2 Department of Medical Pathology, University of California, Davis, California 95616,3 Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 208924

Received 25 October 2007/ Accepted 11 December 2007

Rhesus cytomegalovirus (RhCMV) is an emerging model for human cytomegalovirus (HCMV) pathogenesis that facilitates experimental CMV infection of a natural primate host closely related to humans. We have generated a library of RhCMV mutants with lesions in genes whose HCMV orthologues have been characterized as nonessential for replication in human fibroblasts, and we characterized their replication in rhesus fibroblasts and epithelial cells. The RhCMV mutants grew well in fibroblasts, as predicted by earlier studies with HCMV. However, mutations in four genes caused replication defects in rhesus retinal pigment epithelial cells: Rh01 (an HCMV TRL1 orthologue), Rh159 (HCMV UL148), Rh160 (HCMV UL132), and Rh203 (HCMV US22). Growth of the Rh01-deficient mutant was examined in detail. After entry into epithelial cells, the mutant expressed representative viral proteins, accumulated viral DNA, and generated infectious virus, but it failed to spread efficiently. We conclude that Rh01 is a cell tropism determinant that has the potential to dramatically affect virus spread and pathogenesis.

* Corresponding author. Mailing address: Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544. Phone: (609) 258-5993. Fax: (609) 258-1704. E-mail: alilja{at}princeton.edu

{triangledown} Published ahead of print on 19 December 2007.

Journal of Virology, March 2008, p. 2170-2181, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.02316-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lilja, A. E., Shenk, T. (2008). Efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types. Proc. Natl. Acad. Sci. USA 105: 19950-19955 [Abstract] [Full Text]  


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