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Yasunaga A, Hanna SL, Li J, et al. Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection. PLoS Pathog. 2014;10(2):e1003914doi: 10.1371/journal.ppat.1003914.
Yasunaga, A., Hanna, S. L., Li, J., Cho, H., Rose, P. P., Spiridigliozzi, A., Gold, B., Diamond, M. S., & Cherry, S. (2014). Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection. PLoS pathogens, 10(2), e1003914. https://doi.org/10.1371/journal.ppat.1003914
Yasunaga, Ari, et al. "Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection." PLoS pathogens vol. 10,2 (2014): e1003914. doi: https://doi.org/10.1371/journal.ppat.1003914
Yasunaga A, Hanna SL, Li J, Cho H, Rose PP, Spiridigliozzi A, Gold B, Diamond MS, Cherry S. Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection. PLoS Pathog. 2014 Feb 13;10(2):e1003914. doi: 10.1371/journal.ppat.1003914. eCollection 2014 Feb. PMID: 24550726; PMCID: PMC3923753.
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PLoS Pathog. 2014 Feb 13;10(2):e1003914. doi: 10.1371/journal.ppat.1003914. eCollection 2014 Feb.

Genome-wide RNAi screen identifies broadly-acting host factors that inhibit arbovirus infection.

PLoS pathogens

Ari Yasunaga, Sheri L Hanna, Jianqing Li, Hyelim Cho, Patrick P Rose, Anna Spiridigliozzi, Beth Gold, Michael S Diamond, Sara Cherry

Affiliations

  1. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America ; Penn Genome Frontiers Institute, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
  2. Departments of Medicine, Molecular Microbiology, Pathology & Immunology, Washington University School of Medicine, St Louis, Missouri, United States of America.

PMID: 24550726 PMCID: PMC3923753 DOI: 10.1371/journal.ppat.1003914

Abstract

Vector-borne viruses are an important class of emerging and re-emerging pathogens; thus, an improved understanding of the cellular factors that modulate infection in their respective vertebrate and insect hosts may aid control efforts. In particular, cell-intrinsic antiviral pathways restrict vector-borne viruses including the type I interferon response in vertebrates and the RNA interference (RNAi) pathway in insects. However, it is likely that additional cell-intrinsic mechanisms exist to limit these viruses. Since insects rely on innate immune mechanisms to inhibit virus infections, we used Drosophila as a model insect to identify cellular factors that restrict West Nile virus (WNV), a flavivirus with a broad and expanding geographical host range. Our genome-wide RNAi screen identified 50 genes that inhibited WNV infection. Further screening revealed that 17 of these genes were antiviral against additional flaviviruses, and seven of these were antiviral against other vector-borne viruses, expanding our knowledge of invertebrate cell-intrinsic immunity. Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts.

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