MX2 is an interferon-induced inhibitor of HIV-1 infection
Melissa Kane,Melissa Kane,Shalini S. Yadav,Julia Bitzegeio,Julia Bitzegeio,Sebla B. Kutluay,Sebla B. Kutluay,Trinity Zang,Trinity Zang,Trinity Zang,Sam J. Wilson,John W. Schoggins,John W. Schoggins,Charles M. Rice,Masahiro Yamashita,Theodora Hatziioannou,Paul D. Bieniasz,Paul D. Bieniasz,Paul D. Bieniasz +18 more
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TLDR
Overall, these findings indicate that MX2 is an effector of the anti-HIV-1 activity of type-I IFN, and suggest thatMX2 inhibits HIV-1 infection by inhibiting capsid-dependent nuclear import of subviral complexes.Abstract:
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 IFN. 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 cells. 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.read more
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Interferon-Stimulated Genes: A Complex Web of Host Defenses
TL;DR: This review begins by introducing interferon (IFN) and the JAK-STAT signaling pathway to highlight features that impact ISG production and describes ways in which ISGs both enhance innate pathogen-sensing capabilities and negatively regulate signaling through the Jak-STAT pathway.
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Mx GTPases: dynamin-like antiviral machines of innate immunity
TL;DR: New structural and functional insights are focused on and recent data revealing that human MxA (MX1) provides a safeguard against introduction of avian influenza A viruses into the human population is discussed.
Journal ArticleDOI
HIV-1 and interferons: who's interfering with whom?
TL;DR: The evidence that IFNs can control HIV-1 replication in vivo is discussed and the controversial role of IFNs in promoting the pathological sequelae of chronic HIV- 1 infection is debated.
Journal ArticleDOI
Massively parallel reporter assays of melanoma risk variants identify MX2 as a gene promoting melanoma.
Jiyeon Choi,Tongwu Zhang,Andrew Vu,Julien Ablain,Matthew M. Makowski,Leandro M. Colli,Mai Xu,Rebecca C Hennessey,Jinhu Yin,Harriet Rothschild,Cathrin Gräwe,Michael A. Kovacs,Karen M. Funderburk,Myriam Brossard,John C. Taylor,Bogdan Pasaniuc,Raj Chari,Stephen J. Chanock,Clive J. Hoggart,Florence Demenais,Jennifer H. Barrett,Matthew Law,Mark M. Iles,Kai Yu,Michiel Vermeulen,Leonard I. Zon,Kevin M. Brown +26 more
TL;DR: It is demonstrated that expression of one such gene, MX2, leads to the promotion of melanoma in a zebrafish model, and the integrative approach streamlines GWAS follow-up studies and highlights a pleiotropic function of MX2 in melanoma susceptibility.
Journal ArticleDOI
Identification of Interferon-Stimulated Genes with Antiretroviral Activity
Melissa Kane,Trinity Zang,Suzannah J. Rihn,Fengwen Zhang,Fengwen Zhang,Tonya Kueck,Tonya Kueck,Mudathir Alim,Mudathir Alim,John W. Schoggins,Charles M. Rice,Sam J. Wilson,Paul D. Bieniasz,Paul D. Bieniasz +13 more
TL;DR: Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes.
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Corrigendum: A diverse range of gene products are effectors of the type I interferon antiviral response.
John W. Schoggins,Sam J. Wilson,Maryline Panis,Mary Murphy,Christopher T. Jones,Paul D. Bieniasz,Charles M. Rice +6 more
TL;DR: In this paper, the authors used the WNV-GFP stock used in the data set (Fig. 2 and Supplementary Table 8 of the original Letter) for West Nile virus (WNV) in this Letter was actually Venezuelan equine encephalitis virus (VEEV)-GFP.