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Journal of Virology, April 2000, p. 3586-3597, Vol. 74, No. 8
Howard Hughes Medical Institute and
Departments of Microbiology and Medicine, University of California
San Francisco, San Francisco, California 94143
Received 4 October 1999/Accepted 21 January 2000
Open reading frame (ORF) 57 of Kaposi's sarcoma-associated
herpesvirus (KSHV) encodes a homolog of known posttranscriptional regulators that are essential for replication in other herpesviruses. Here, we examined the expression of this gene and the function(s) of
its product. KSHV ORF 57 is expressed very early in infection from a
1.6-kb spliced RNA bearing several in-frame initiation codons. Its
product is a nuclear protein that, in transient assays, has little
effect on the expression of luciferase reporter genes driven by a
variety of KSHV and heterologous promoters. However, ORF 57 protein
enhances the accumulation of several viral transcripts, in a manner
suggesting posttranscriptional regulation. These transcripts include
not only known cytoplasmic mRNAs (e.g., ORF 59) but also a nuclear RNA
(nut-1) that lacks coding potential. Finally, ORF 57 protein can also
modulate the effects of the ORF 50 gene product, a classical
transactivator known to be required for lytic induction. The expression
from some (e.g., nut-1) but not all (e.g., tk) ORF 50-responsive
promoters can be synergistically enhanced by coexpression of ORF 50 and
ORF 57. This effect is not due to upregulation of ORF 50 expression but
rather to a posttranslational enhancement of the transcriptional
activity of ORF 50. These data indicate that ORF 57 is a powerful
pleiotropic effector that can act on several posttranscriptional levels
to modulate the expression of viral genes in infected cells.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Kaposi's Sarcoma-Associated Herpesvirus Open
Reading Frame 57 Encodes a Posttranscriptional Regulator with
Multiple Distinct Activities
*
Corresponding author. Mailing address: Departments of
Microbiology and Medicine, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143. Phone: (415) 476-2826. Fax:
(415) 476-0939. E-mail: ganem{at}cgl.ucsf.edu.
This paper is dedicated to the memory of Rob Sadler, our colleague
and friend.
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