1887

Abstract

Human herpesvirus-8 (HHV-8) is aetiologically linked to Kaposi's sarcoma and primary effusion lymphoma. Although interferon- (IFN-) and interferon- (IFN-) are both antiviral cytokines, IFN- blocks entry of HHV-8 into the lytic phase, whereas IFN- induces 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- and IFN- induced 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- than with IFN-, whereas IFN- induced higher levels of IRF-1 than did IFN-. IFN- induced 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- was present during TPA stimulation, the production of infectious virus was reduced by at least a 60 %, and IFN- fully blocked TPA-induced production of infectious virus. The greater reduction of viral production that occurred with IFN- is consistent with the higher levels of the antiviral proteins PKR and 2′5′-OAS induced by IFN- than by IFN-. These studies indicate that the augmentation of cellular antiviral defences by IFN- was sufficient to prevent production of infectious virus despite IFN--induced entry of some cells into the lytic phase of HHV-8 replication.

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2004-10-01
2020-01-18
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