This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Monini, P.
Right arrow Articles by Ensoli, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Monini, P.
Right arrow Articles by Ensoli, B.

 Previous Article  |  Next Article 

Journal of Virology, May 1999, p. 4029-4041, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Alpha Interferon Inhibits Human Herpesvirus 8 (HHV-8) Reactivation in Primary Effusion Lymphoma Cells and Reduces HHV-8 Load in Cultured Peripheral Blood Mononuclear Cells

Paolo Monini,1 Francesca Carlini,1 Michael Stürzl,2 Paola Rimessi,3 Fabiana Superti,4 Marina Franco,1 Gianna Melucci-Vigo,1 Aurelio Cafaro,1 Delia Goletti,1 Cecilia Sgadari,1 Stefano Butto',1 Patrizia Leone,1 Pasqualina Leone,1 Chiara Chiozzini,1 Caterina Barresi,5 Antonella Tinari,4 Angela Bonaccorsi,3 Maria R. Capobianchi,5 Massimo Giuliani,6 Aldo di Carlo,6 Massimo Andreoni,7 Giovanni Rezza,8 and Barbara Ensoli1,*

Laboratory of Virology,1 Laboratory of Ultrastructure,4 and Centro Operativo AIDS,8 Istituto Superiore di Sanità, Institute of Virology, University "La Sapienza",5 S. Gallicano Hospital,6 and School of Medicine, University "Tor Vergata",7 Rome, and Section of Microbiology, Department of Diagnostic and Experimental Medicine, University of Ferrara, Ferrara,3 Italy, and Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Neuherberg, and Institute of Virology, Technical University of Munich, Munich, Germany2

Received 27 July 1998/Accepted 25 January 1999

Infection by human herpesvirus 8 (HHV-8) is associated with the development of Kaposi's sarcoma (KS). Since regression of KS can be achieved by treatment of the patients with alpha interferon (IFN-alpha ), we analyzed the effects of IFN-alpha or anti-IFN-alpha antibodies (Ab) on HHV-8 latently infected primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on peripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-alpha inhibited in a dose-dependent manner the amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection with tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1 and kaposin genes that are induced early and several hours, respectively, after TPA treatment. In addition, IFN-alpha inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-1 and kaposin genes by IFN-alpha was also observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti-IFN-alpha Ab to TPA-induced BCBL-1 cells resulted in a larger number of mature enveloped particles and in a more extensive cytopathic effect due to the neutralization of the endogenous IFN produced by these cells. IFN was also produced by cultured PBMC from HHV-8-infected individuals, and this was associated with a loss of viral DNA during culture. However, the addition of anti-IFN-alpha Ab or anti-type I IFN receptor Ab promoted the maintenance of HHV-8 DNA in these cells that was associated with the detection of the latency-associated kaposin RNA. Finally, the addition of IFN-alpha reduced the HHV-8 load in PBMC. Thus, IFN-alpha appears to have inhibitory effects on HHV-8 persistent infection of PBMC. These results suggest that, in addition to inhibiting the expression of angiogenic factors that are key to KS development, IFN-alpha may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation.

* Corresponding author. Mailing address: Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 39-06-49903209. Fax: 39-06-49387184. E-mail: ensoli{at}virus1.net.iss.it.

Journal of Virology, May 1999, p. 4029-4041, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Perry, S. T., Compton, T. (2006). Kaposi's Sarcoma-Associated Herpesvirus Virions Inhibit Interferon Responses Induced by Envelope Glycoprotein gpK8.1. J. Virol. 80: 11105-11114 [Abstract] [Full Text]  
  • Xu, D., Brumm, K., Zhang, L. (2006). The Latent Membrane Protein 1 of Epstein-Barr Virus (EBV) Primes EBV Latency Cells for Type I Interferon Production. J. Biol. Chem. 281: 9163-9169 [Abstract] [Full Text]  
  • Barton, E. S., Lutzke, M. L., Rochford, R., Virgin, H. W. IV (2005). Alpha/Beta Interferons Regulate Murine Gammaherpesvirus Latent Gene Expression and Reactivation from Latency. J. Virol. 79: 14149-14160 [Abstract] [Full Text]  
  • Wang, J., Zhang, J., Zhang, L., Harrington, W. Jr., West, J. T., Wood, C. (2005). Modulation of Human Herpesvirus 8/Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Activator Transactivation by Interferon Regulatory Factor 7. J. Virol. 79: 2420-2431 [Abstract] [Full Text]  
  • Pozharskaya, V. P., Weakland, L. L., Offermann, M. K. (2004). Inhibition of infectious human herpesvirus 8 production by gamma interferon and alpha interferon in BCBL-1 cells. J. Gen. Virol. 85: 2779-2787 [Abstract] [Full Text]  
  • Pozharskaya, V. P., Weakland, L. L., Zimring, J. C., Krug, L. T., Unger, E. R., Neisch, A., Joshi, H., Inoue, N., Offermann, M. K. (2004). Short Duration of Elevated vIRF-1 Expression during Lytic Replication of Human Herpesvirus 8 Limits Its Ability To Block Antiviral Responses Induced by Alpha Interferon in BCBL-1 Cells. J. Virol. 78: 6621-6635 [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]  
  • Broccolo, F., Bossolasco, S., Careddu, A. M., Tambussi, G., Lazzarin, A., Cinque, P. (2002). Detection of DNA of Lymphotropic Herpesviruses in Plasma of Human Immunodeficiency Virus-Infected Patients: Frequency and Clinical Significance. CVI 9: 1222-1228 [Abstract] [Full Text]  
  • Ablashi, D. V., Chatlynne, L. G., Whitman, J. E. Jr., Cesarman, E. (2002). Spectrum of Kaposi's Sarcoma-Associated Herpesvirus, or Human Herpesvirus 8, Diseases. Clin. Microbiol. Rev. 15: 439-464 [Abstract] [Full Text]  
  • Zhu, F. X., King, S. M., Smith, E. J., Levy, D. E., Yuan, Y. (2002). A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation. Proc. Natl. Acad. Sci. USA 99: 5573-5578 [Abstract] [Full Text]  
  • Giuliani, M., Mastroianni, A., Di Carlo, A., Donati, P., Miceli, M., Monini, P., Rezza, G. (2002). Onset of Non-AIDS Kaposi Sarcoma During Therapy With Interferon Alfa-2a in an 82-Year-Old Man With Concomitant Cutaneous T-Cell Lymphoma. Arch Dermatol 138: 535-537 [Full Text]  
  • Rimessi, P., Bonaccorsi, A., Sturzl, M., Fabris, M., Brocca-Cofano, E., Caputo, A., Melucci-Vigo, G., Falchi, M., Cafaro, A., Cassai, E., Ensoli, B., Monini, P. (2001). Transcription Pattern of Human Herpesvirus 8 Open Reading Frame K3 in Primary Effusion Lymphoma and Kaposi's Sarcoma. J. Virol. 75: 7161-7174 [Abstract] [Full Text]  
  • Lubyova, B., Pitha, P. M. (2000). Characterization of a Novel Human Herpesvirus 8-Encoded Protein, vIRF-3, That Shows Homology to Viral and Cellular Interferon Regulatory Factors. J. Virol. 74: 8194-8201 [Abstract] [Full Text]  
  • Rezza, G., Dorrucci, M., Andreoni, M., Arpino, C., De Luca, A., Monini, P., Nicastri, E., Alliegro, M. B., Pezzotti, P., Ensoli, B. (1999). Does HHV-8 have a protective role on the development of HIV encephalopathy?. Neurology 53: 2032-2032 [Abstract] [Full Text]  
  • Rezza, G., Andreoni, M., Dorrucci, M., Pezzotti, P., Monini, P., Zerboni, R., Salassa, B., Colangeli, V., Sarmati, L., Nicastri, E., Barbanera, M., Pristera, R., Aiuti, F., Ortona, L., Ensoli, B. (1999). Human Herpesvirus 8 Seropositivity and Risk of Kaposi's Sarcoma and Other Acquired Immunodeficiency Syndrome-Related Diseases. JNCI J Natl Cancer Inst 91: 1468-1474 [Abstract] [Full Text]  
  • Monini, P., Colombini, S., Sturzl, M., Goletti, D., Cafaro, A., Sgadari, C., Butto, S., Franco, M., Leone, P., Fais, S., Leone, P., Melucci-Vigo, G., Chiozzini, C., Carlini, F., Ascherl, G., Cornali, E., Zietz, C., Ramazzotti, E., Ensoli, F., Andreoni, M., Pezzotti, P., Rezza, G., Yarchoan, R., Gallo, R. C., Ensoli, B. (1999). Reactivation and Persistence of Human Herpesvirus-8 Infection in B Cells and Monocytes by Th-1 Cytokines Increased in Kaposi's Sarcoma. Blood 93: 4044-4058 [Abstract] [Full Text]  
  • Zhu, F. X., King, S. M., Smith, E. J., Levy, D. E., Yuan, Y. (2002). A Kaposi's sarcoma-associated herpesviral protein inhibits virus-mediated induction of type I interferon by blocking IRF-7 phosphorylation and nuclear accumulation. Proc. Natl. Acad. Sci. USA 99: 5573-5578 [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»