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Cited by 375interferon and immune responsesRNA and protein synthesis mechanismsHIV Research and Treatment

Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11

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Li, Manqing, Kao, Elaine, Gao, Xia, Sandig, Hilary, Limmer, Kirsten, Pavon-Eternod, Mariana, Jones, Thomas E., Landry, Sebastien +3 more·2012·Nature
DOI 10.1038/nature11433PMC PMC3705913
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Abstract

In mammals, one of the most pronounced consequences of viral infection is the induction of type I interferons, cytokines with potent antiviral activity. Schlafen (Slfn) genes are a subset of interferon-stimulated early response genes (ISGs) that are also induced directly by pathogens via the interferon regulatory factor 3 (IRF3) pathway. However, many ISGs are of unknown or incompletely understood function. Here we show that human SLFN11 potently and specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1). Our study revealed that SLFN11 has no effect on the early steps of the retroviral infection cycle, including reverse transcription, integration and transcription. Rather, SLFN11 acts at the late stage of virus production by selectively inhibiting the expression of viral proteins in a codon-usage-dependent manner. We further find that SLFN11 binds transfer RNA, and counteracts changes in the tRNA pool elicited by the presence of HIV. Our studies identified a novel antiviral mechanism within the innate immune response, in which SLFN11 selectively inhibits viral protein synthesis in HIV-infected cells by means of codon-bias discrimination.

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  • Of the five human Schlafen isoforms, two (Schlafen 11 and Schlafen 13) were identified as inhibitory factors for HIV-1.

    “Of the five human Schlafen isoforms, two (Schlafen 11 and Schlafen 13) were identified as inhibitory factors for HIV-1 (106, 108).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [106]

    The paper reports that SLFN11 inhibits HIV-1 production, supporting one of the two named factors. It does not identify SLFN13 as an HIV-1 inhibitory factor, and its introductory passage says there are six human SLFN genes, not five (both passages are labeled Abstract in our copy; no page is given). (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Schlafen 11 expression is induced by interferon, whereas Hili expression is a result of T-cell activation.

    “Although there appears to be high similarity between Hili-and Schlafen 11-mediated inhibition of HIV-1, Schlafen 11 expression is induced by interferon, whereas Hili expression is a result of T-cell activation (106, 114).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [106]

  • Human Schlafen 11 protein inhibits HIV-1 gene expression via intrinsic properties of the transcripts.

    “Indeed, the human Schlafen 11 protein was reported to inhibit HIV-1 gene expression via intrinsic properties of the transcripts (106).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [106]

  • Human Schlafen 11 binds to tRNAs and selectively inhibits HIV-1 gene expression in a codon usage-based manner.

    “Human Schlafen 11, a putative DNA/RNA helicase with regulatory roles in cancer cell lines (109 -111), binds to tRNAs and selectively inhibits HIV-1 gene expression in a codon usage-based manner (106).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [106]

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Research works printed but not linked: 28

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Authors
Li, M., Kao, E., Gao, X., Sandig, H., Limmer, K., Pavon-Eternod, M., Jones, T. E., Landry, S., Pan, T., Weitzman, M. D., & David, M.
Affiliations
  • University of California San Diego (US)
  • University of Chicago (US)
  • Salk Institute for Biological Studies (US)
Corresponding author
David, Michael
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2012-09-23
Volume
491
Issue
7422
Pages
125-128
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature11433
PMC
PMC3705913
OpenAlex
W1974786493
Cited by
375
References
0
Citations by year
2026: 18 · 2025: 32 · 2024: 34 · 2023: 34 · 2022: 20 · 2021: 36 · 2020: 20 · 2019: 33 · 2018: 27 · 2017: 28 · 2016: 16 · 2015: 24 · 2014: 25 · 2013: 23 · 2012: 5
FWCI
10.77
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM101982)
  • National Institute of Allergy and Infectious Diseases (P30AI 36214, P01AI090935, AI074967, R21AI088490, R01AI074967, R21AI081019, P30AI036214, AI81019)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords
Schlafen 11, SLFN11, HIV-1, codon usage bias, tRNA binding, antiviral innate immunity, interferon-stimulated genes, rare codons, viral protein synthesis inhibition, type I interferon, retroviral infection
MeSH terms
Cell Line, Cells, Cultured, Codon, Humans, Immunity, Innate, Nuclear Proteins, RNA, Transfer, RNA, Viral, Species Specificity, Substrate Specificity, Protein Biosynthesis, Viral Proteins, HIV-1, Gene Expression Regulation, Viral, Virus Integration, Reverse Transcription, HEK293 Cells

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