This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rimessi, P.
Right arrow Articles by Monini, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rimessi, P.
Right arrow Articles by Monini, P.

 Previous Article  |  Next Article 

Journal of Virology, August 2001, p. 7161-7174, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7161-7174.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Transcription Pattern of Human Herpesvirus 8 Open Reading Frame K3 in Primary Effusion Lymphoma and Kaposi's Sarcoma

Paola Rimessi,1 Angela Bonaccorsi,1 Michael Stürzl,2 Marina Fabris,1 Egidio Brocca-Cofano,1 Antonella Caputo,1 Gianna Melucci-Vigo,3 Mario Falchi,4 Aurelio Cafaro,3 Enzo Cassai,1 Barbara Ensoli,3,* and Paolo Monini3

Section of Microbiology, Department of Diagnostic and Experimental Medicine, University of Ferrara, 44100 Ferrara,1 and Laboratories of Virology3 and Ultrastructure,4 Istituto Superiore di Sanità, 00161 Rome, Italy, and Institute of Molecular Virology, GSF-National Research Center for Environment and Health, 85764 Neuherberg, Germany2

Received 30 January 2001/Accepted 30 April 2001

Human herpesvirus 8 (HHV-8) is found in immunoblastic B cells of patients with multicentric Castleman's disease (MCD) and, predominantly in a latent form, in primary effusion lymphoma (PEL) cells and Kaposi's sarcoma (KS) spindle cells. Recent studies have shown that upon reactivation, HHV-8 expresses factors that downregulate major histocompatibility class I proteins and coactivation molecules and that may enable productively infected cells to escape cytotoxic T lymphocytes and natural killer cell responses. One of these viral factors is encoded by open reading frame (ORF) K3. Here we show that in PEL cells, ORF K3 is expressed through viral transcripts that are induced very early upon virus reactivation, including bicistronic RNA molecules containing coding sequences from viral ORFs K3 and 70. Specifically, we found that a bicistronic transcript was expressed in the absence of de novo protein synthesis, thereby identifying a novel HHV-8 immediate-early gene product. Several features of the RNA molecules encoding the K3 product, including multiple transcriptional start sites, multiple donor splicing sites, and potential alternative ATG usage, suggest that there exists a finely tuned modulation of ORF K3 expression. By contrast, ORF K3 transcripts are not detected in the majority of cells present in KS lesions that are latently infected by the virus, suggesting that there are other, as-yet-unknown mechanisms of immune evasion for infected KS spindle cells. Nevertheless, because HHV-8 viremia precedes the development of KS lesions and is associated with the recrudescence of MCD symptoms, the prompt expression of ORF K3 in productively infected circulating cells may be important for virus pathogenesis. Thus, molecules targeting host or viral factors that activate ORF K3 expression or inactivate the biological functions of the K3 product should be exploited for the prevention or treatment of HHV-8-associated diseases in at-risk individuals.

* Corresponding author. Mailing address: Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 39-06-49903209. Fax: 39-06-49903002. E-mail: ensoli{at}iss.it.

Journal of Virology, August 2001, p. 7161-7174, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.7161-7174.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Majerciak, V., Yamanegi, K., Zheng, Z.-M. (2006). Gene Structure and Expression of Kaposi's Sarcoma-Associated Herpesvirus ORF56, ORF57, ORF58, and ORF59. J. Virol. 80: 11968-11981 [Abstract] [Full Text]  
  • Ribechini, E., Fortini, C., Marastoni, M., Traniello, S., Spisani, S., Monini, P., Gavioli, R. (2006). Identification of CD8+ T Cell Epitopes within Lytic Antigens of Human Herpes Virus 8. J. Immunol. 176: 923-930 [Abstract] [Full Text]  
  • Taylor, J. L., Bennett, H. N., Snyder, B. A., Moore, P. S., Chang, Y. (2005). Transcriptional Analysis of Latent and Inducible Kaposi's Sarcoma-Associated Herpesvirus Transcripts in the K4 to K7 Region. J. Virol. 79: 15099-15106 [Abstract] [Full Text]  
  • Coleman, H. M., Brierley, I., Stevenson, P. G. (2003). An Internal Ribosome Entry Site Directs Translation of the Murine Gammaherpesvirus 68 MK3 Open Reading Frame. J. Virol. 77: 13093-13105 [Abstract] [Full Text]  
  • Dourmishev, L. A., Dourmishev, A. L., Palmeri, D., Schwartz, R. A., Lukac, D. M. (2003). Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 175-212 [Abstract] [Full Text]  
  • Ahn, J. W., Powell, K. L., Kellam, P., Alber, D. G. (2002). Gammaherpesvirus Lytic Gene Expression as Characterized by DNA Array. J. Virol. 76: 6244-6256 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»