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Cited by 76Evolution and Genetic DynamicsImmune Response and Inflammationinterferon and immune responses

Patterns of oligonucleotide sequences in viral and host cell RNA identify mediators of the host innate immune system

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Greenbaum, Benjamin D., Rabadan, Raul, Levine, Arnold J.·2009·PLoS ONE
DOI 10.1371/journal.pone.0005969PMC PMC2694999
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Abstract

The innate immune response provides a first line of defense against pathogens by targeting generic differential features that are present in foreign organisms but not in the host. These innate responses generate selection forces acting both in pathogens and hosts that further determine their co-evolution. Here we analyze the nucleic acid sequence fingerprints of these selection forces acting in parallel on both host innate immune genes and ssRNA viral genomes. We do this by identifying dinucleotide biases in the coding regions of innate immune response genes in plasmacytoid dendritic cells, and then use this signal to identify other significant host innate immune genes. The persistence of these biases in the orthologous groups of genes in humans and chickens is also examined. We then compare the significant motifs in highly expressed genes of the innate immune system to those in ssRNA viruses and study the evolution of these motifs in the H1N1 influenza genome. We argue that the significant under-represented motif pattern of CpG in an AU context--which is found in both the ssRNA viruses and innate genes, and has decreased throughout the history of H1N1 influenza replication in humans--is immunostimulatory and has been selected against during the co-evolution of viruses and host innate immune genes. This shows how differences in host immune biology can drive the evolution of viruses that jump into species with different immune priorities than the original host.

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  • An alternate hypothesis proposes that CpG dinucleotides are the sole cause of attenuation because they act as triggers of antiviral immune responses.

    “Thus, an alternate hypothesis proposes that CpG dinucleotides are the sole cause of attenuation because they act as triggers of antiviral immune responses (Greenbaum et al., 2009).”

    From Mechanism of Virus Attenuation by Codon Pair Deoptimization (2020) · cites this paper as Greenbaum et al., 2009

    The Discussion (page unavailable) proposes that CpG-containing RNA motifs can trigger an innate immune response. But the paper does not say CpG dinucleotides are the sole cause of attenuation; its Results specify that CpGs in an A/U context, rather than all CpGs, are preferentially selected against. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • During adaptation viruses often change their genome structure according to the genome features of their new hosts.

    “During adaptation viruses often change their genome structure according to the genome features of their new hosts (Greenbaum et al., 2009).”

    From Codon Pair Bias Is a Direct Consequence of Dinucleotide Bias (2016) · cites this paper as Greenbaum et al., 2009

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References 39 · Cited by 76

Research works printed but not linked: 33

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Authors
Greenbaum, B. D., Rabadan, R., & Levine, A. J.
Affiliations
Institute for Advanced Study (US)
Corresponding author
Greenbaum, Benjamin D.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-06-18
Volume
4
Issue
6
Pages
e5969
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0005969
PMC
PMC2694999
OpenAlex
W2084733358
Cited by
76
References
39
Citations by year
2026: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 11 · 2020: 11 · 2019: 1 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 8 · 2012: 6
FWCI
2.14
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
Keywords
innate immunity, host-virus coevolution, CpG motifs, plasmacytoid dendritic cells, innate immunity genes, ssRNA viruses, H1N1 influenza, viral evolution, chickens, sequence motifs
MeSH terms
Animals, Chickens, Influenza in Birds, Humans, Immune System, Immunity, Innate, Influenza, Human, Oligonucleotides, Probability, RNA Viruses, RNA, Viral, Genome, CpG Islands, Amino Acid Motifs, Gene Expression Profiling

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