兩個(gè)小組在本期Nature上報(bào)告說(shuō),，人類(lèi)干擾素誘導(dǎo)的GTP結(jié)合蛋白MX2是“1-型人免疫缺陷病毒” (HIV-1) 和若干種其他慢病毒的一個(gè)強(qiáng)效抑制因子,。
人們多年前就知道,，與其相關(guān)的蛋白MX1在人體中能抑制HIV-1復(fù)制，但MX2過(guò)去卻被認(rèn)為沒(méi)有抗病毒活性,。
MX2的抗HIV-1活性對(duì)GTP酶的依賴(lài)性要遠(yuǎn)遠(yuǎn)小于MX1更廣泛的抗病毒活性對(duì)GTP酶的依賴(lài)性,，說(shuō)明二者之間可能存在機(jī)制上的差別。（生物谷Bioon.com）
生物谷推薦的英文摘要
Nature doi:10.1038/nature12542
Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection
Caroline Goujon,，Olivier Moncorgé,，Hélène Bauby，Tomas Doyle,，Christopher C. Ward,，Torsten Schaller，Stéphane Hué,，Wendy S. Barclay,，Reiner Schulz& Michael H. Malim
Animal cells harbour multiple innate effector mechanisms that inhibit virus replication. For the pathogenic retrovirus human immunodeficiency virus type 1 (HIV-1)， these include widely expressed restriction factors1,， such as APOBEC3 proteins2,， TRIM5-α3,， BST2 (refs 4,， 5) and SAMHD1 (refs 6， 7),， as well as additional factors that are stimulated by type 1 interferon (IFN)8,， 9， 10,， 11,， 12， 13,， 14. Here we use both ectopic expression and gene-silencing experiments to define the human dynamin-like,， IFN-induced myxovirus resistance 2 (MX2， also known as MXB) protein as a potent inhibitor of HIV-1 infection and as a key effector of IFN-α-mediated resistance to HIV-1 infection. MX2 suppresses infection by all HIV-1 strains tested， has equivalent or reduced effects on divergent simian immunodeficiency viruses,， and does not inhibit other retroviruses such as murine leukaemia virus. The Capsid region of the viral Gag protein dictates susceptibility to MX2,， and the block to infection occurs at a late post-entry step， with both the nuclear accumulation and chromosomal integration of nascent viral complementary DNA suppressed. Finally,， human MX1 (also known as MXA),， a closely related protein that has long been recognized as a broadly acting inhibitor of RNA and DNA viruses， including the orthomyxovirus influenza A virus15,， 16,， does not affect HIV-1， whereas MX2 is ineffective against influenza virus. MX2 is therefore a cell-autonomous,， anti-HIV-1 resistance factor whose purposeful mobilization may represent a new therapeutic approach for the treatment of HIV/AIDS.
MX2 is an interferon-induced inhibitor of HIV-1 infection
doi:10.1038/nature12653
Melissa Kane,，Shalini S. Yadav，Julia Bitzegeio,，Sebla B. Kutluay,，Trinity Zang，Sam J. Wilson,，John W. Schoggins,，Charles M. Rice，Masahiro Yamashita,，Theodora Hatziioannou& Paul D. Bieniasz
HIV-1 replication can be inhibited by type I interferon (IFN),， and the expression of a number of gene products with anti-HIV-1 activity is induced by type I IFN1， 2. However,， none of the known antiretroviral proteins can account for the ability of type I IFN to inhibit early,， preintegration phases of the HIV-1 replication cycle in human cells3， 4. Here,， by comparing gene expression profiles in cell lines that differ in their ability to support the inhibitory action of IFN-α at early steps of the HIV-1 replication cycle,， we identify myxovirus resistance 2 (MX2) as an interferon-induced inhibitor of HIV-1 infection. Expression of MX2 reduces permissiveness to a variety of lentiviruses， whereas depletion of MX2 using RNA interference reduces the anti-HIV-1 potency of IFN-α. HIV-1 reverse transcription proceeds normally in MX2-expressing cells,， but 2-long terminal repeat circular forms of HIV-1 DNA are less abundant,， suggesting that MX2 inhibits HIV-1 nuclear import， or destabilizes nuclear HIV-1 DNA. Consistent with this notion,， mutations in the HIV-1 capsid protein that are known,， or suspected， to alter the nuclear import pathways used by HIV-1 confer resistance to MX2,， whereas preventing cell division increases MX2 potency. Overall,， these findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN， and suggest that MX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.
