Influenza Virus-Host Interactome Screen as a Platform for Antiviral Drug Development
Open accessAbstract
Host factors required for viral replication are ideal drug targets because they are less likely than viral proteins to mutate under drug-mediated selective pressure. Although genome-wide screens have identified host proteins involved in influenza virus replication, limited mechanistic understanding of how these factors affect influenza has hindered potential drug development. We conducted a systematic analysis to identify and validate host factors that associate with influenza virus proteins and affect viral replication. After identifying over 1,000 host factors that coimmunoprecipitate with specific viral proteins, we generated a network of virus-host protein interactions based on the stage of the viral life cycle affected upon host factor downregulation. Using compounds that inhibit these host factors, we validated several proteins, notably Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) and JAK1, as potential antiviral drug targets. Thus, virus-host interactome screens are powerful strategies to identify targetable host factors and guide antiviral drug development.
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Knowledge of temporal virus-host interactions can identify viral or host factors that are targetable in antiviral therapeutics.
“knowledge of temporal virus–host interactions can also reveal viral or host factors that can be targeted in antiviral therapeutics.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [21]
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- Authors
- Watanabe, T., Kawakami, E., Shoemaker, J. E., Lopes, T. J. S., Matsuoka, Y., Tomita, Y., Kozuka-Hata, H., Gorai, T., Kuwahara, T., Takeda, E., Nagata, A., Takano, R., Kiso, M., Yamashita, M., Sakai-Tagawa, Y., Katsura, H., Nonaka, N., Fujii, H., Fujii, K., Sugita, Y., Noda, T., Goto, H., Fukuyama, S., Watanabe, S., Neumann, G., Oyama, M., Kitano, H., & Kawaoka, Y.
- Affiliations
- Japan Science and Technology Agency (JP)
- University of Wisconsin–Madison (US)
- Institute of Medical Science, The University of Tokyo (JP)
- University of Miyazaki (JP)
- Okinawa Institute of Science and Technology Graduate University (JP)
- Corresponding author
- Kawaoka, Yoshihiro
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 16
- Issue
- 6
- Pages
- 795-805
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC4451456
- OpenAlex
- W2011226251
- Cited by
- 290
- References
- 57
- Citations by year
- 2026: 20 · 2025: 24 · 2024: 16 · 2023: 15 · 2022: 20 · 2021: 31 · 2020: 26 · 2019: 34 · 2018: 28 · 2017: 30 · 2016: 31 · 2015: 14 · 2013: 1
- FWCI
- 18.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health, Department of Health and Human Services (HHSN272200800060C)
- ERATO
- Japan Science and Technology Agency
- Chugai Pharmaceuticals
- Daiichi Sankyo Pharmaceutical
- Toyama Chemical
- Tauns Laboratories, Inc.
- Otsuka Pharmaceutical Co., Ltd
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- influenza virus, host factors, antiviral drug targets, viral replication, co-immunoprecipitation, protein-protein interaction, viral life cycle, GBF1, JAK1
- MeSH terms
- Antiviral Agents, Drug Evaluation, Preclinical, Humans, Influenza, Human, Orthomyxoviridae, Protein Binding, Viral Proteins, Guanine Nucleotide Exchange Factors, Protein Interaction Mapping, Janus Kinase 1, Host-Pathogen Interactions, Protein Interaction Maps
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