Inhibition of infectious human herpesvirus 8 production by gamma interferon and alpha interferon in BCBL-1 cells

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Abstract
Human herpesvirus-8 (HHV-8) is aetiologically linked to Kaposi's sarcoma and primary effusion lymphoma. Although interferon-α(IFN-α) and interferon-γ(IFN-γ) are both antiviral cytokines, IFN-αblocks entry of HHV-8 into the lytic phase, whereas IFN-γinduces an increase in the percentage of cells undergoing lytic replication. Multiple events in the lytic cascade must be completed to produce infectious virus. The ability of both types of IFN to affect the production of infectious virus was explored. Both IFN-αand IFN-γinduced expression of the antiviral proteins double-stranded RNA-activated protein kinase (PKR) and 2′5′-oligoadenylate synthetase (2′5′-OAS) in HHV-8-infected BCBL-1 cells. Higher levels resulted from incubation with IFN-αthan with IFN-γ, whereas IFN-γinduced higher levels of IRF-1 than did IFN-α. IFN-γinduced a minor increase in lytic viral gene expression, which was not accompanied by a detectible increase in infectious virus. When lytic replication of HHV-8 was induced using TPA, high levels of infectious virus appeared in the conditioned medium. When IFN-γwas present during TPA stimulation, the production of infectious virus was reduced by at least a 60 %, and IFN-αfully blocked TPA-induced production of infectious virus. The greater reduction of viral production that occurred with IFN-αis consistent with the higher levels of the antiviral proteins PKR and 2′5′-OAS induced by IFN-αthan by IFN-γ. These studies indicate that the augmentation of cellular antiviral defences by IFN-γwas sufficient to prevent production of infectious virus despite IFN-γ-induced entry of some cells into the lytic phase of HHV-8 replication.