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Journal of Virology, December 1999, p. 10040-10050, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Cytomegalovirus UL144 Open Reading Frame: Sequence Hypervariability in Low-Passage Clinical Isolates

Nell S. Lurain,1,* Kathi S. Kapell,1 Diana D. Huang,1 Jeffery A. Short,1 Jeanette Paintsil,1 Ernest Winkfield,1 Chris A. Benedict,2 Carl F. Ware,2 and James W. Bremer1

Department of Immunology/Microbiology, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612,1 and Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California 921212

Received 17 June 1999/Accepted 1 September 1999

Human cytomegalovirus (HCMV) infects a number of organs and cell types in vivo, leading to the hypothesis that HCMV disease and tissue tropism may be related to specific sequence variants. A potential component of HCMV variant strains is the UL144 open reading frame (ORF), which encodes a homologue of the herpesvirus entry mediator, HveA, a member of the tumor necrosis factor receptor superfamily. Sequence analysis of the UL144 ORF in 45 low-passage clinical isolates demonstrated significant strain-specific variability. In individual isolates, nucleotide substitutions occur at up to 21% of the 531 positions, resulting in approximately the same percentage of substitutions in the predicted 176-amino-acid sequence. Phylogenetic analysis indicated that the nucleotide and amino acid sequences diverge into three major groups. For genotypic comparison, the known hypervariable region encompassing the proteolytic cleavage site of the glycoprotein B (gB) gene was also sequenced. All of the isolates could be typed according to the four known gB groups; however, the gB and UL144 sequence groups appeared to be phylogenetically unlinked. The predicted UL144 product homology with tumor necrosis factor receptor family members, along with the unexpectedly high level of sequence variability of the UL144 ORF, suggests that the predicted product may play a role in HCMV infectivity and subsequent host disease.

* Corresponding author. Mailing address: Department of Immunology/Microbiology, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Pkwy., Chicago, IL 60612. Phone: (312) 942-8734. Fax: (312) 942-2808. E-mail: nlurain{at}rush.edu.

Journal of Virology, December 1999, p. 10040-10050, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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