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Equine MX2 is a restriction factor of equine infectious anemia virus (EIAV).
Abstract: Human myxovirus resistance protein B (hMXB) is a restriction factor of HIV-1 that also inhibits a variety of retroviruses. However, hMXB is not antiviral against equine infectious anemia virus (EIAV). We show here that equine MX2 (eMX2) potently restricts EIAV in vitro. Additionally, eMX2 inhibits HIV-1 and other lentiviruses, including murine leukemia virus. Previously, it was reported that hMXB repression is reduced in hMXB Δ1-25, but not in GTP-binding mutant K131A and GTP-hydrolysis mutant T151A. In contrast to this phenomenon, our study indicates that eMX2 restriction is not diminished in eMX2 Δ1-25, but is in eMX2 K127A and T147A, which correspond to hMXB K131A and T151A, respectively. Thus, eMX2 may inhibit retroviral replication by a novel mechanism that differs from that of hMXB.
Copyright © 2018 Elsevier Inc. All rights reserved.
Publication Date: 2018-08-03 PubMed ID: 30081309DOI: 10.1016/j.virol.2018.07.024Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research study investigates the role of the equine MX2 protein in inhibiting the replication of equine infectious anemia virus (EIAV) and other similar viruses, demonstrating a different mechanism of action compared to its human counterpart (hMXB).
Introduction and Objectives
- This study focuses on understanding how the equine MX2 (eMX2) protein restricts the equine infectious anemia virus (EIAV) as well as other lentiviruses, including the human immunodeficiency virus (HIV-1).
- The researchers aim to compare the functioning of eMX2 with that of its human counterpart, the human myxovirus resistance protein B (hMXB), specifically, to identify potential novel mechanisms of viral inhibition.
Findings and Discussion
- The research demonstrated that while hMXB operates as a restriction factor for HIV-1 and various other retroviruses, it does not show antiviral activity against EIAV. In contrast, eMX2 was shown to restrict EIAV potently.
- Moreover, eMX2 was found to inhibit other lentiviruses, including HIV-1 and murine leukemia virus, hinting at its broader antiviral properties.
- Previous studies noted that specific mutations in hMXB (hMXB Δ1-25, K131A, and T151A) affected its ability to restrain viruses. However, analogous mutations in eMX2 demonstrated different outcomes: the eMX2 Δ1-25 mutation did not lessen eMX2’s restriction ability, but the K127A and T147A mutations did.
- These contrasting observations suggest that eMX2 operates via a different mechanism compared to hMXB in inhibiting viral replication. This proposes a novel antiviral strategy that could be explored for therapeutic benefits.
Implications and Future Directions
- While the article significantly advances our understanding of the antiviral mechanisms of eMX2, further studies are needed to fully establish the biochemical details of these mechanisms.
- Deciphering this novel inhibition strategy could lead to the development of new antiviral drugs useful in treating EIAV and other lentivirus infections, potentially including HIV.
Cite This Article
APA
Meier K, Jaguva Vasudevan AA, Zhang Z, Bähr A, Kochs G, Häussinger D, Münk C.
(2018).
Equine MX2 is a restriction factor of equine infectious anemia virus (EIAV).
Virology, 523, 52-63.
https://doi.org/10.1016/j.virol.2018.07.024 Publication
Researcher Affiliations
- Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
- Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
- Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
- Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
- Institute of Virology, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Herman-Herder-Str. 1, 79104 Freiburg, Germany.
- Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
- Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address: carsten.muenk@med.uni-duesseldorf.de.
MeSH Terms
- Amino Acid Substitution
- Animals
- Base Sequence
- Binding Sites
- Gene Expression
- Genetic Vectors / chemistry
- Genetic Vectors / metabolism
- Guanosine Triphosphate / metabolism
- HIV-1 / genetics
- HIV-1 / growth & development
- HIV-1 / metabolism
- Horses
- Host-Pathogen Interactions
- Humans
- Infectious Anemia Virus, Equine / genetics
- Infectious Anemia Virus, Equine / growth & development
- Infectious Anemia Virus, Equine / metabolism
- Lentivirus / genetics
- Lentivirus / metabolism
- Mutation
- Myxovirus Resistance Proteins / genetics
- Myxovirus Resistance Proteins / metabolism
- Protein Binding
- Recombinant Proteins / genetics
- Recombinant Proteins / metabolism
- Signal Transduction
Citations
This article has been cited 11 times.- Wang XF, Zhang X, Ma W, Li J, Wang X. Host cell restriction factors of equine infectious anemia virus. Virol Sin 2023 Aug;38(4):485-496.
- Betancor G. You Shall Not Pass: MX2 Proteins Are Versatile Viral Inhibitors. Vaccines (Basel) 2023 May 3;11(5).
- Saito A, Yamashita M. HIV-1 capsid variability: viral exploitation and evasion of capsid-binding molecules. Retrovirology 2021 Oct 26;18(1):32.
- Lyu S, Yuan X, Liu L, Zhang H, Yu Z, Hang X, Shi W, Wu Y. Application of a recombinant replicase to localize the Trionyx sinensis hemorrhagic syndrome virus and evaluate its effects on antiviral genes of T. sinensis. J Zhejiang Univ Sci B 2021 Apr 15;22(4):295-304.
- Boso G, Kozak CA. Retroviral Restriction Factors and Their Viral Targets: Restriction Strategies and Evolutionary Adaptations. Microorganisms 2020 Dec 11;8(12).
- Twizerimana AP, Scheck R, Becker D, Zhang Z, Wammers M, Avelar L, Pflieger M, Häussinger D, Kurz T, Gohlke H, Münk C. Cell Type-Dependent Escape of Capsid Inhibitors by Simian Immunodeficiency Virus SIVcpz. J Virol 2020 Nov 9;94(23).
- Xie L, Ju Z, Zhong C, Wu Y, Zan Y, Hou W, Feng Y. GTPase Activity of MxB Contributes to Its Nuclear Location, Interaction with Nucleoporins and Anti-HIV-1 Activity. Virol Sin 2021 Feb;36(1):85-94.
- Alvarez FJD, Zhang P. Purification and Characterization of MxB. Methods Mol Biol 2020;2159:55-65.
- Staeheli P, Haller O. Human MX2/MxB: a Potent Interferon-Induced Postentry Inhibitor of Herpesviruses and HIV-1. J Virol 2018 Dec 15;92(24).
- Schimmich C, Vabret A, Zientara S, Valle-Casuso JC. Equine Infectious Anemia Virus Cellular Partners Along the Viral Cycle. Viruses 2024 Dec 24;17(1).
- Wang T, Becker D, Twizerimana AP, Luedde T, Gohlke H, Münk C. Cyclophilin A Regulates Tripartite Motif 5 Alpha Restriction of HIV-1. Int J Mol Sci 2025 Jan 9;26(2).
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