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Journal of Virology, July 1999, p. 5926-5933, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Human Herpesvirus 6 Open Reading Frame U83 Encodes a Functional Chemokine

Ping Zou,1 Yuji Isegawa,1 Kazusi Nakano,1 M. Haque,1 Yasuhiko Horiguchi,2 and Koichi Yamanishi1,*

Department of Microbiology, Osaka University Medical School,1 and Department of Toxicology, Research Institute for Microbial Diseases, Osaka University,2 Suita, Osaka 565-0871, Japan

Received 23 December 1998/Accepted 7 April 1999

Some viruses including herpesviruses have undergone evolution to benefit viral infection and propagation by pirating and modifying host genes such as chemokine genes. Human herpesvirus 6 (HHV-6), acutely or persistently infects mononuclear cells in vitro. DNA sequence analysis of HHV-6 has revealed that the putative protein encoded by an open reading frame (ORF) of the U83 gene in HHV-6 variant B resembled a human chemokine. We have cloned the U83 gene and analyzed the biological function of this gene. The U83 gene contained an ORF encoding a 113-amino-acid peptide, starting at the first methionine and containing a possible signal peptide and the typical cysteine residues characteristic of the chemokines. Reverse transcription-PCR analysis of mRNA and immunofluorescent-antibody testing of infected cells both indicated that the encoded protein was a late protein. The ORF U83 gene fused to the Fc gene was expressed as a fusion protein in COS-7 cells by transfection, and the fusion protein was purified from the supernatant of transfected cells to test its biological function. The purified protein was capable of inducing transient calcium mobilization in THP-1 cells and of chemotactically activating THP-1 cells. These findings suggested that the U83 protein might play an important role in HHV-6 propagation in vivo by activating and trafficking mononuclear cells to sites of viral replication, thus aiding the development of superbly efficient virus production mechanisms.

* Corresponding author. Mailing address: Department of Microbiology, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-3321. Fax: 81-6-6879-3329. E-mail: yamanisi{at}micro.med.osaka-u.ac.jp.

Journal of Virology, July 1999, p. 5926-5933, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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