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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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