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Journal of Virology, June 2006, p. 5251-5260, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02570-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Kaposi's Sarcoma-Associated Herpesvirus Lytic Gene ORF57 Is Essential for Infectious Virion Production

Zhao Han1 and Sankar Swaminathan1,2*

Program in Cancer Genetics, Epigenetics and Tumor Virology, UF Shands Cancer Center,1 Division of Infectious Diseases, Department of Internal Medicine, University of Florida, Gainesville, Florida 32610-02322

Received 9 December 2005/ Accepted 15 March 2006

The ORF57 gene of Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a nuclear protein expressed during the lytic phase of KSHV replication. An ORF57 homolog is present in all known human herpesviruses and many animal herpesviruses. Many of these proteins have been demonstrated to have essential transcriptional and posttranscriptional regulatory functions. ORF57 enhances expression of reporter genes posttranscriptionally in vitro and may synergize with transcription factors to enhance gene transcription. However, the biologic role of ORF57 in KSHV replication has not been established. In this study, we demonstrate that ORF57 is essential for productive KSHV lytic replication by constructing a recombinant KSHV in which ORF57 expression has been specifically inactivated. The ORF57-null KSHV recombinant was unable to produce virion progeny or fully express several other lytic KSHV genes except when ORF57 was provided in trans. The Epstein-Barr virus (EBV) homolog of ORF57, SM, was unable to rescue lytic KSHV virion production, although EBV SM does enhance KSHV lytic gene expression from the ORF57-null mutant. Conversely, ORF57 did not rescue an SM-null recombinant EBV, indicating the existence of virus-specific functions for the ORF57 family of genes.

* Corresponding author. Mailing address: UF Shands Cancer Center, Box 100232, University of Florida, Gainesville, FL 32610-0232. Phone: (352) 846-1151. Fax: (352) 392-5802. E-mail: sswamina{at}ufl.edu.

Journal of Virology, June 2006, p. 5251-5260, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.02570-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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