• 3878 Citations
1973 …2015

Research output per year

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Personal profile

Research interests

RNA viruses have high mutation rates and large population sizes that produce an astonishing diversity of variants that allow them to adapt rapidly to a particular lifecycle, conceivably to become optimal, such that the extant wildtype sequence is more fit than any variants derived from it. Analyses of viral sequences show that significant portions of their proteins are extremely well conserved: frequently shared by all viruses in the same genus. The corresponding RNA sequences typically contain many synonymous changes, indicating that mutations do occur at these sites, but no amino acid changes became fixed, suggesting that no neutral nor beneficial nonsynonymous changes exist at these sites. We use Sindbis virus as a model system to test if RNA viruses are indeed extremely well-adapted, and thus largely resistant to change. We examined the viral promoter that is used for the production of the subgenomic mRNA synthesis, using in vivo evolution and mutagenesis approaches, to show that across most of the promoter, the wildtype sequence is the most fit; i.e., the promoter is essentially optimal. Similar approaches will be used to test if much of the protein sequence of the viruses are similarly optimal. The results to date suggest a novel and general approach for designing antiviral drugs, by targeting the conserved protein and RNA sequences of the viruses. It promises to provide broad-spectrum antiviral drugs that are effective against the virus and that have minimal impact on host processes, with very low probabilities of drug-resistance.

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Research Output

  • 3878 Citations
  • 52 Article
  • 2 Review article
  • 1 Chapter
  • 1 Comment/debate

Drosophila Muller F elements maintain a distinct set of genomic properties over 40 million years of evolution

Participating Students and Faculty of the Genomics Education Partnership, 2015, In : G3: Genes, Genomes, Genetics. 5, 5, p. 719-740 22 p.

Research output: Contribution to journalArticle

Open Access
  • 53 Scopus citations

    Bacterial Nucleoid-Associated protein uncouples transcription levels from transcription timing

    Zwir, I., Yeo, W. S., Shin, D., Latifi, T., Huang, H. & Groisman, E. A., Oct 7 2014, In : mBio. 5, 5, e01485-14.

    Research output: Contribution to journalArticle

    Open Access
  • 24 Scopus citations

    Adaptive immunity restricts replication of novel murine astroviruses

    Yokoyama, C. C., Loh, J., Zhao, G., Stappenbeck, T. S., Wang, D., Huang, H. V., Virgin, H. W. & Thackray, L. B., Nov 2012, In : Journal of virology. 86, 22, p. 12262-12270 9 p.

    Research output: Contribution to journalArticle

    Open Access
  • 42 Scopus citations

    Intrinsic Negative Feedback Governs Activation Surge in Two-Component Regulatory Systems

    Yeo, W. S., Zwir, I., Huang, H. V., Shin, D., Kato, A. & Groisman, E. A. G., Mar 30 2012, In : Molecular cell. 45, 6, p. 844 1 p.

    Research output: Contribution to journalComment/debate

    Open Access
    3 Scopus citations

    Intrinsic Negative Feedback Governs Activation Surge in Two-Component Regulatory Systems

    Yeo, W. S., Zwir, I., Huang, H. V., Shin, D., Kato, A. & Groisman, E. A., Feb 10 2012, In : Molecular cell. 45, 3, p. 409-421 13 p.

    Research output: Contribution to journalArticle

    Open Access
  • 25 Scopus citations