Catalytic turnover of STAT1 allows PIV5 to dismantle the interferon-induced anti-viral state of cells.

A dynamic model of degradation by the V protein of parainfluenza virus 5 (PIV5; formerly SV5) has been proposed. In it, the V protein functions as a bipartite adaptor linking DDB1, a component of a cellular SCF-like ubiquitin E3 ligase complex, to which in turn binds duanyu18131 and presents duanyu18131 to the E3 ligase complex for ubiquitination and subsequent degradation. Furthermore, it appears that loss of duanyu18131 from the complex results in decreased affinity of V for such that duanyu18132 either dissociates from V or is displaced by complexes, facilitating the cycling of the DDB1/PIV5 V containing E3 complex for further rounds of duanyu18131 ubiquitination and degradation. By determining the approximate number of molecules of V, DDB1, duanyu18131 and duanyu18132 present in IFN-treated 2fTGH cells, we provide additional evidence for this dynamic model of duanyu18131 degradation. These results show that (i) in IFN-treated cells there is approximately 4-fold less duanyu18132 and 15-fold less DDB1 than duanyu18131 per cell and thus DDB1 and duanyu18132 must repeatedly acquire more duanyu18131 for degradation to go to completion, and (ii) approximately 600 molecules of V protein per cell can target as many as 120,000 molecules of duanyu18131 for degradation in the absence of either viral or cellular protein synthesis. The importance of this mechanism in terms of the ability of the virus to dismantle the IFN-induced anti-viral state of cells is discussed.

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