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Prediction of human protein interactome of dengue virus non-structural protein 5 (NS5) and its downstream immunological implications

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Abstract

The non-structural protein 5 (NS5) is the most conserved protein among flaviviruses, a family that includes the dengue virus. It functions both as an RNA-dependent RNA polymerase and an RNA-methyltransferase and is therefore essential for the replication of viral RNA. The discovery that dengue virus NS5 protein (DENV-NS5) can also localize to the nucleus has resulted in renewed interest in its potential roles at the host-virus interface. In this study, we have used two complementary computational approaches in parallel – one based on linear motifs (ELM) and another based on tertiary structure of the protein (DALI) – to predict the host proteins that DENV-NS5 might interact with. Of the 42 human proteins predicted by both these methods, 34 are novel. Pathway analysis of these 42 human proteins shows that they are involved in key host cellular processes related to cell cycle regulation, proliferation, protein degradation, apoptosis, and immune responses. A focused analysis of transcription factors that directly interact with the predicted DENV-NS5 interacting proteins was performed, followed by the identification of downstream genes that are differentially expressed after dengue infection using previously published RNA-seq data. Our study provides unique insights into the DENV-NS5 interaction network and delineates mechanisms whereby DENV-NS5 could impact the host-virus interface. The novel interactors identified in this study could be potentially targeted by NS5 to modulate the host cellular environment in general, and the immune response in particular, thereby extending the role of DENV-NS5 beyond its known enzymatic functions.

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All data supporting the findings of this study are available within the paper and its Supplementary Information.

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Acknowledgements

We would like to thank Dr. Sakshi Chaudhary (ICGEB, New Delhi) and Love Panchariya (ICGEB, New Delhi) for their valuable inputs at the time of manuscript revision.

Funding

The authors did not receive support from any organization for the submitted work.

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Author notes

  1. Prashant Bajpai and Jatin Shrinet have contributed equally to this work.

Authors and Affiliations

  1. Department of Biotechnology, TERI School of Advanced Studies, New Delhi, India

    Priya Bhatnagar & Ramakrishnan Sitaraman

  2. ICGEB-Emory Vaccine Centre, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

    Priya Bhatnagar, Prashant Bajpai, Murali Krishna Kaja & Anmol Chandele

  3. Department of Biological Science, Florida State University, Tallahassee, FL, 32306, USA

    Jatin Shrinet

  4. Department of Pediatrics and Emory Vaccine Centre, Emory University School of Medicine, Atlanta, GA, USA

    Murali Krishna Kaja

Authors
  1. Priya Bhatnagar
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  2. Prashant Bajpai
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  3. Jatin Shrinet
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  4. Murali Krishna Kaja
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  5. Anmol Chandele
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  6. Ramakrishnan Sitaraman
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Contributions

Conceptualization and design of pipeline was done by JS and PB. Data curation and analysis was done by PB. RNA-seq data curation and analysis was done by PB. Figures were made by PB and PB. PB wrote the first draft. Rewriting, reviewing and editing were done by PB, MKK, AC and RS.

Corresponding authors

Correspondence to Priya Bhatnagar, Anmol Chandele or Ramakrishnan Sitaraman.

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This research does not involve human participants and/or animals.

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Bhatnagar, P., Bajpai, P., Shrinet, J. et al. Prediction of human protein interactome of dengue virus non-structural protein 5 (NS5) and its downstream immunological implications. 3 Biotech 13, 180 (2023). https://doi.org/10.1007/s13205-023-03569-0

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  • DOI: https://doi.org/10.1007/s13205-023-03569-0

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