Abstract
The innate type I interferon antiviral response is the first line of defence invoked to limit the spread of viral infections. Hence a number of viruses including Kaposi's sarcoma-associated herpesvirus (KSHV) have evolved defence strategies against this antiviral response. KSHV is the aetiologic agent of KS and almost one quarter of the KSHV genes specify either demonstrated or potential immunomodulatory activity including the four viral interferon regulatory factors (vIRFs). vIRFs 1, 2 and 3 have previously been shown to inhibit type I IFN signalling, whereas the inhibitory role of vIRF4 is yet to be reported. A previous stable isotope labelling of amino acids in cell culture (SILAC) study coupled to LC-MS/MS identified USP7 and ribosomal proteins as binding partners of both vIRF2 and vIRF4. The aim of the present study was to investigate the role of these binding partners in type I IFN signalling and to determine the regulatory mechanisms behind the effects of these partner proteins on the functions of the vIRF2 and vIRF4 proteins. Polysome profiling and microarray studies were carried out on vIRF4 expressing cells and suggested a novel regulatory role for vIRF4 in translation. USP7 was also characterised as a positive regulator of IFN signalling and the mechanism behind this effect was explored.