HUMAN MXB PROTEIN, AN INTERFERON-ALPHA-INDUCIBLE GTPASE, CONTAINS A NUCLEAR TARGETING SIGNAL AND IS LOCALIZED IN THE HETEROCHROMATIN REGIONBENEATH THE NUCLEAR-ENVELOPE

Interferon-inducible Mx proteins belong to the family of large GTPases and are highly homologous with dynamins within their GTP-binding doma in. Cytoplasmically localized human MxA protein mediates resistance to influenza and several other viruses, whereas human MxB protein has no t been found to have any antiviral activity. Here we show that MxB pro tein is found both in the cytoplasm and in the nucleus, where it is lo calized in a granular pattern in the heterochromatin region beneath th e nuclear envelope. Transfection experiments in COS cells of N-termina lly deleted MxB constructs revealed a functional nuclear localization signal within the first 24 N-terminal amino acids. Nuclear 78-kDa and cytoplasmic 76-kDa forms of MxB protein were found in all of the cell lines studied and in human peripheral blood mononuclear cells. MxB pro tein proved to be a functional GTPase with activity comparable to that of MxA protein. N-terminally truncated (Delta 1-82) MxB protein lacki ng both the nuclear localization signal and a proline-rich domain had almost completely lost its GTPase activity. Analysis of peripheral blo od mononuclear cells suggested that MxB protein expression is strictly regulated by interferon-alpha. This is the first documentation that h uman Mx protein resides in the nucleus. It also emphasizes that there are considerable differences in the localization and structure of func tional domains within Mx proteins.