Equine schlafen 11 restricts the production of equine infectious anemia virus via a codon usage-dependent mechanism.
Abstract: Human schlafen11 is a novel restriction factor for HIV-1 based on bias regarding relative synonymous codon usage (RSCU). Here, we report the cloning of equine schlafen11 (eSLFN11) and the characteristics of its role in restricting the production of equine infectious anemia virus (EIAV), a retrovirus similar to HIV-1. Overexpression of eSLFN11 inhibited EIAV replication, whereas knockdown of endogenous eSLFN11 by siRNA enhanced the release of EIAV from its principal target cell. Notably, although eSLFN11 significantly suppressed expression of viral Gag protein and EIAV release into the culture medium, the levels of intracellular viral early gene proteins Tat and Rev and viral genomic RNA were unaffected. Coincidently, similar altered patterns of codon usage bias were observed for both the early and late genes of EIAV. Therefore, our data suggest that eSLFN11 restricts EIAV production by impairing viral mRNA translation via a mechanism that is similar to that employed by hSLFN11 for HIV-1.
Copyright © 2016 Elsevier Inc. All rights reserved.
Publication Date: 2016-05-18 PubMed ID: 27200480DOI: 10.1016/j.virol.2016.04.024Google 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
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research explores how equine schlafen11, a horse-based gene, can hamper the replication of equine infectious anemia virus, an HIV-1-like virus.
Overview of Research
In this study, scientists cloned the gene equine schlafen11, also known as eSLFN11, to understand its role in fighting off the equine infectious anemia virus (EIAV). The research draws parallels to the human equivalent of the gene, human schlafen11 (hSLFN11), which is known to obstruct the HIV-1 virus.
Key Findings and Methodology
- The researchers found that increasing the presence of eSLFN11 within a cell led to the restriction of EIAV replication.
- Inversely, when the eSLFN11 gene was suppressed via siRNA, a type of molecule known to silence gene expression, the release of EIAV from its target cell was notably enhanced.
- The effect of eSLFN11, however, didn’t influence the early stage viral proteins, Tat and Rev, and the viral genomic RNA, indicating that its restriction mechanism is specific to certain parts of the virus’s life cycle.
Significance of the Codon Usage Pattern
- The researchers observed specific patterns of codon usage bias, a phenomenon where specific codons (sequences of three DNA or RNA nucleotides) are favored over others, in both early and late genes of EIAV.
- This observation led the researchers to propose that eSLFN11 hinders EIAV by impairing the translation of viral mRNA, a process that creates proteins using genes’ instructions.
- The manner in which eSLFN11 impedes EIAV production is likened to the way hSLFN11 restricts HIV-1, lending further credence to the theory that these genes could be utilized therapeutically in future treatments.
Implications and Future Research
- The findings in this study may lead to the development of new antiviral therapies that exploit SLFN11 or other similar genes’ virus restriction capabilities.
- Further research is needed to fully understand the mechanism of eSLFN11 and how it can be optimized for maximum viral restriction. Additionally, other potential genes with similar properties could also be investigated.
Cite This Article
APA
Lin YZ, Sun LK, Zhu DT, Hu Z, Wang XF, Du C, Wang YH, Wang XJ, Zhou JH.
(2016).
Equine schlafen 11 restricts the production of equine infectious anemia virus via a codon usage-dependent mechanism.
Virology, 495, 112-121.
https://doi.org/10.1016/j.virol.2016.04.024 Publication
Researcher Affiliations
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China. Electronic address: sndhr@163.com.
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China. Electronic address: sunlk0916@126.com.
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China; College of Wildlife Resources, Northeast Forestry University, Harbin, China. Electronic address: zhudantong123@163.com.
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China. Electronic address: huzher@126.com.
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China. Electronic address: xuefengwang1982@126.com.
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China. Electronic address: chengdᦁ@163.com.
- Department of Geriatrics And Gerontology, First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: wang_yu_hong@163.com.
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China. Electronic address: xjw@hvri.ac.cn.
- Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Science, Harbin, China. Electronic address: jianhua_uc@126.com.
MeSH Terms
- Amino Acid Sequence
- Animals
- Codon
- Gene Expression Regulation, Viral
- Gene Knockdown Techniques
- Genome, Viral
- HIV-1 / physiology
- Horses
- Humans
- Infectious Anemia Virus, Equine / physiology
- Nuclear Proteins / chemistry
- Nuclear Proteins / genetics
- Nuclear Proteins / metabolism
- RNA, Small Interfering / genetics
- RNA, Viral
- Transcription, Genetic
- Viral Proteins / chemistry
- Viral Proteins / genetics
- Viral Proteins / metabolism
- Virus Release
- Virus Replication
Citations
This article has been cited 23 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.
- Hou P, Hao W, Qin B, Li M, Zhao R, Cui S. Structural and biochemical characterization of Schlafen11 N-terminal domain. Nucleic Acids Res 2023 Jul 21;51(13):7053-7070.
- Kim ET, Weitzman MD. Schlafens Can Put Viruses to Sleep. Viruses 2022 Feb 21;14(2).
- Wang Y, Ma G, Wang XF, Na L, Guo X, Zhang J, Liu C, Du C, Qi T, Lin Y, Wang X. Keap1 recognizes EIAV early accessory protein Rev to promote antiviral defense. PLoS Pathog 2022 Feb;18(2):e1009986.
- Nightingale K, Potts M, Hunter LM, Fielding CA, Zerbe CM, Fletcher-Etherington A, Nobre L, Wang ECY, Strang BL, Houghton JW, Antrobus R, Suarez NM, Nichols J, Davison AJ, Stanton RJ, Weekes MP. Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex. Proc Natl Acad Sci U S A 2022 Feb 8;119(6).
- Al-Marsoummi S, Vomhof-DeKrey EE, Basson MD. Schlafens: Emerging Proteins in Cancer Cell Biology. Cells 2021 Aug 29;10(9).
- Chintala K, Mohareer K, Banerjee S. Dodging the Host Interferon-Stimulated Gene Mediated Innate Immunity by HIV-1: A Brief Update on Intrinsic Mechanisms and Counter-Mechanisms. Front Immunol 2021;12:716927.
- Yue T, Zhan X, Zhang D, Jain R, Wang KW, Choi JH, Misawa T, Su L, Quan J, Hildebrand S, Xu D, Li X, Turer E, Sun L, Moresco EMY, Beutler B. SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity. Science 2021 May 14;372(6543).
- Boso G, Kozak CA. Retroviral Restriction Factors and Their Viral Targets: Restriction Strategies and Evolutionary Adaptations. Microorganisms 2020 Dec 11;8(12).
- Bergantz L, Subra F, Deprez E, Delelis O, Richetta C. Interplay between Intrinsic and Innate Immunity during HIV Infection. Cells 2019 Aug 17;8(8).
- Valdez F, Salvador J, Palermo PM, Mohl JE, Hanley KA, Watts D, Llano M. Schlafen 11 Restricts Flavivirus Replication. J Virol 2019 Aug 1;93(15).
- Chen J, Kuhn LA. Deciphering the three-domain architecture in schlafens and the structures and roles of human schlafen12 and serpinB12 in transcriptional regulation. J Mol Graph Model 2019 Jul;90:59-76.
- Jin D, Musier-Forsyth K. Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication. J Biol Chem 2019 Apr 5;294(14):5352-5364.
- de Pablo-Maiso L, Doménech A, Echeverría I, Gómez-Arrebola C, de Andrés D, Rosati S, Gómez-Lucia E, Reina R. Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses. Viruses 2018 Aug 17;10(8).
- Basson MD, Wang Q, Chaturvedi LS, More S, Vomhof-DeKrey EE, Al-Marsoummi S, Sun K, Kuhn LA, Kovalenko P, Kiupel M. Schlafen 12 Interaction with SerpinB12 and Deubiquitylases Drives Human Enterocyte Differentiation. Cell Physiol Biochem 2018;48(3):1274-1290.
- Wang HN, Rao D, Fu XQ, Hu MM, Dong JG. Equine infectious anemia virus in China. Oncotarget 2018 Jan 2;9(1):1356-1364.
- Seong RK, Seo SW, Kim JA, Fletcher SJ, Morgan NV, Kumar M, Choi YK, Shin OS. Schlafen 14 (SLFN14) is a novel antiviral factor involved in the control of viral replication. Immunobiology 2017 Nov;222(11):979-988.
- Peterlin BM, Liu P, Wang X, Cary D, Shao W, Leoz M, Hong T, Pan T, Fujinaga K. Hili Inhibits HIV Replication in Activated T Cells. J Virol 2017 Jun 1;91(11).
- Chen SM, Ma L, Wang Z, Li QJ, Zhou R, Wang J, Ding JW, Zhao JY, Yi DR, Zhang YX, Guo SS, Wang XL, Li XY, Liu ZL, Cen S. SLFN14 functions as a P-TEFb inhibitor to modulate the transcription of HIV-1 and cellular genes. Sci Adv 2025 Dec 19;11(51):eadt7982.
- Coleman KE, Shin DW, Goehring L, Szeitz B, Fenyö D, Rothenberg E, Poirier JT, Huang TT. SLFN11 counteracts the RFWD3-PRIMPOL DNA damage tolerance axis to restrain gapped DNA synthesis in response to replication stress. Nat Commun 2025 Dec 10;16(1):11029.
- Mordier J, Fraisse M, Cohen-Tannoudji M, Molaro A. Recurrent Evolutionary Innovations in Rodent and Primate Schlafen Genes. Genome Biol Evol 2025 Sep 30;17(10).
- 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).
- Jäger N, Pöhlmann S, Rodnina MV, Ayyub SA. Interferon-Stimulated Genes that Target Retrovirus Translation. Viruses 2024 Jun 8;16(6).
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
