A monomeric GTPase-negative MxA mutant with antiviral activity

MxA is a large, interferon-induced GTPase with antiviral activity against R NA viruses. It forms large oligomers, but whether oligomerization and GTPas e activity are important for antiviral function is not known. The mutant pr otein MxA (L612K) carries a lysine-for-leucine substitution at position 612 and fails to form oligomers. Here we show that monomeric MxA(L612K) tacks detectable GTPase activity but is capable of inhibiting Thogoto virus in tr ansiently transfected Vero cells or in a Thogoto virus minireplicon system. Likewise, MxA (L612K) inhibited vesicular stomatitis virus multiplication. These findings indicate that MxA monomers are antivirally active and sugge st that GTP hydrolysis may not be required for antiviral activity. MxA(L612 K) is rapidly degraded in cells, whereas wild-type MxA is stable. We propos e that high-molecular-weight MxA oligomers represent a stable intracellular pool from which active MxA monomers are recruited.