Murine AKAP7 has a 2′, 5′-phosphodiesterase domain that can complement an inactive murine coronavirus ns2 gene

Viral 2=,5=-phosphodiesterases (2=,5=-PDEs) help disparate RNA viruses evade the antiviral activity of interferon (IFN)by degrading 2=,5=-oligoadenylate (2-5A) activators of RNase L. A kinase anchoring proteins (AKAPs) bind the regulatory subunits of protein kinase A (PKA) to localize and organize cyclic AMP (cAMP) signaling during diverse physiological processes.Among more than 43 AKAP isoforms, AKAP7 appears to be unique in its homology to viral 2=,5=-PDEs. Here we show thatmouse AKAP7 rapidly degrades 2-5A with kinetics similar to that of murine coronavirus (mouse hepatitis virus [MHV]) strainA59 ns2 and human rotavirus strain WA VP3 proteins. To determine whether AKAP7 could substitute for a viral 2=,5=-PDE, weinserted AKAP7 cDNA into an MHV genome with an inactivated ns2 gene. The AKAP7 PDE domain or N-terminally truncatedAKAP7 (both lacking a nuclear localization motif), but not full-length AKAP7 or a mutant, AKAP7H185R, PDE domain restoredthe infectivity of ns2 mutant MHV in bone marrow macrophages andin livers of infected mice. Interestingly, the AKAP7 PDEdomain and N-terminally deleted AKAP7 were present in the cytoplasm (the site of MHV replication), whereas full-lengthAKAP7 was observed only in nuclei. We suggest the possibility that viral acquisition of the host AKAP7 PDE domain might haveoccurred during evolution, allowing diverse RNA viruses to antagonize the RNase L pathway