Janzen C, Kochs G, Haller O
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, D-79008 Freiburg, Germany.
J Virol. 2000 Sep;74(17):8202-6. doi: 10.1128/jvi.74.17.8202-8206.2000.
MxA is a large, interferon-induced GTPase with antiviral activity against RNA viruses. It forms large oligomers, but whether oligomerization and GTPase activity are important for antiviral function is not known. The mutant protein MxA(L612K) carries a lysine-for-leucine substitution at position 612 and fails to form oligomers. Here we show that monomeric MxA(L612K) lacks detectable GTPase activity but is capable of inhibiting Thogoto virus in transiently 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 suggest that GTP hydrolysis may not be required for antiviral activity. MxA(L612K) is rapidly degraded in cells, whereas wild-type MxA is stable. We propose that high-molecular-weight MxA oligomers represent a stable intracellular pool from which active MxA monomers are recruited.
MxA是一种大型的、由干扰素诱导产生的GTP酶，对RNA病毒具有抗病毒活性。它能形成大型寡聚体，但寡聚化和GTP酶活性对抗病毒功能是否重要尚不清楚。突变蛋白MxA(L612K)在612位发生了亮氨酸被赖氨酸取代的情况，无法形成寡聚体。在此我们表明，单体MxA(L612K)缺乏可检测到的GTP酶活性，但能够在瞬时转染的Vero细胞或Thogoto病毒微型复制子系统中抑制Thogoto病毒。同样，MxA(L612K)也抑制水泡性口炎病毒的增殖。这些发现表明MxA单体具有抗病毒活性，并提示抗病毒活性可能不需要GTP水解。MxA(L612K)在细胞中迅速降解，而野生型MxA则是稳定的。我们提出，高分子量的MxA寡聚体代表了一个稳定的细胞内池，从中招募有活性的MxA单体。
