Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection.

Caroline Goujon, Olivier Moncorge, He´le`ne Bauby, Tomas Doyle, Christopher C. Ward, Torsten Schaller, Ste´phane Hue´, Wendy S. Barclay, Reiner Schulz & Michael H. Malim. Nature. (2013) 502, 559-562.

Speaker: Ji-En Sie (謝季恩)                                                 Time: 14:00~15:00, Dec. 25, 2013

Commentator: Dr. Shian-Wei Wang (王憲威博士)             Place: Room 601

Abstract:

The human myxovirus resistance 2 (MX2) protein induced by interferon (IFN) is a factor which involves in anti-HIV-1 infection. IFN-α that belongs to type 1 IFN is known as an inhibitor of replication in many viruses, and activates a signaling cascade, leading to the downstream gene expression (1). MX2 stimulated by IFN-α is one of the anti-viral factors and inhibits HIV-1 nuclear entry or makes nuclear HIV-1 DNA unstable (2). To define the role of MX2 in the IFN-α-mediated anti-viral state, the authors used gene silencing to shut down MX2 expression and also compared to the absence of IFN-α, and found that MX2 silencing stimulated infection and MX2 had no effect without IFN-α. It means that the suppression of HIV-1 requires not only IFN-α but also MX2. In the other hand, the authors used the MX2-expressing vectors transduced cell to confirm MX2-mediated inhibition of viral gene expression, nuclear accumulation and integration of HIV-1 reverse transcripts. In the following experiments, the authors used different primate lentiviruses and non-primate viruses to demonstrate that the MX2 protein didn’t inhibits other viruses except for the HIV-1. Furthermore, the authors measured the effect of MX2 while the cells carried mutant vectors in the Capsid (CA) region of the viral Gag protein and found that HIV-1 CA can influence MX2 sensitivity and may be a target of MX2. Finally, the authors think that the MX2 is a potential HIV-1 resistance factor and may be an other new therapy for HIV and AIDS.

References:

1.     Der SD, Zhou A, Williams BR, Silverman RH. (1998) Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc. Natl. Acad. Sci. U. S. A. 95, 15623-15628.

2.     Melissa Kane, Shalini S. Yadav, Julia Bitzegeio, Sebla B. Kutluay, Trinity Zang, Sam J.Wilson, John W. Schoggins, Charles M. Rice, Masahiro Yamashita, Theodora Hatziioannou1 & Paul D.Bieniasz. (2013) MX2 is an interferon-induced inhibitor of HIV-1 infection. Nature. 502, 563-566.