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, Francesca Carlini, Michael Stürzl, Paola Rimessi, Fabiana Superti, Marina Franco, Gianna Melucci-Vigo, Aurelio Cafaro, Delia Goletti, Cecilia Sgadari, Stefano Butto', Patrizia Leone, Pasqualina Leone, Chiara Chiozzini, Caterina Barresi, Antonella Tinari, Angela Bonaccorsi, Maria R. Capobianchi, Massimo Giuliani, Aldo Di CarloMassimo Andreoni, Giovanni Rezza, Barbara Ensoli

Research output: Contribution to journalArticlepeer-review

Abstract

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-α), we analyzed the effects of IFN-α or anti-IFN-α 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-α 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-α inhibited virus production and/or release from BCBL-1 cells. Inhibition of nut-I and kaposin genes by IFN-α was also observed in BC-1 cells induced with n-butyrate. Conversely, the addition of anti-IFN-α 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-α 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-α reduced the HHV-8 load in PBMC. Thus, IFN-α 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-α may induce KS regression by reducing the HHV-8 load and/or inhibiting virus reactivation.

Original languageEnglish
Pages (from-to)4029-4041
Number of pages13
JournalJournal of Virology
Volume73
Issue number5
Publication statusPublished - 1999

ASJC Scopus subject areas

  • Immunology

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this