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

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 treatm ent of the patients with alpha interferon (IFN-alpha), we analyzed the effe cts of IFN-alpha or anti-IFN-alpha antibodies (Ab) on HHV-8 latently infect ed primary effusion lymphoma-derived cell lines (BCBL-1 and BC-1) and on pe ripheral blood mononuclear cells (PBMC) from patients with all forms of KS and from at-risk subjects. IFN-alpha inhibited in a dose-dependent manner t he amplification of HHV-8 DNA in BCBL-1 cells induced to lytic infection wi th tetradecanoyl phorbol acetate (TPA). This effect was associated with the inhibition of the expression of HHV-8 nut-1 and kaposin genes that are ind uced early and several hours, respectively, after TPA treatment. In additio n, IFN-alpha inhibited virus production and/or release from BCBL-1 cells. I nhibition 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 envelo ped particles and in a more extensive cytopathic effect due to the neutrali zation 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 D NA in these cells that was associated with the detection of the latency-ass ociated kaposin RNA. Finally, the addition of IFN-alpha reduced the HHV-8 l oad in PBMC. Thus, IFN-alpha appears to have inhibitory effects on HHV-8 pe rsistent infection of PBMC. These results suggest that, in addition to inhi biting 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 inhib iting virus reactivation.