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RNAi screening reveals new players in the defense against RNA viruses
Author(s) -
Xu Jie,
Sabin Leah,
Zhou Rui,
Han Greg,
Cherry Sara
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.941.5
Subject(s) - rna interference , biology , innate immune system , rna , drosophila melanogaster , gene silencing , virus , virology , rna silencing , viral replication , small interfering rna , gene , immune system , genetics
Virus‐host interactions are a delicate interplay of opposing forces: the virus subverts cellular machinery to promote its replication while the host mounts an immune response to eliminate the infection. Innate immunity is the first and most ancient line of defense, yet little is known about the cellular factors that restrict viral infection. Our lab uses RNAi screening in cells of Drosophila melanogaster, a model organism that only has an innate immune system, to identify novel antiviral factors. Of particular interest to us are pan‐antiviral factors that restrict arthropod‐borne viruses, for which there is significant morbidity and mortality worldwide due to the lack of vaccines or therapeutics. Using this approach, we previously identified Ars2, which restricts human arthropod‐borne viruses via the antiviral RNA silencing pathway. To find additional antiviral factors, we screened a panel of genes involved in various aspects of RNA metabolism against 4 RNA viruses, including 2 arthropod‐borne pathogens. We focused on genes whose depletion by RNAi leads to increased infection by at least 3 of the 4 viruses tested. We found that factors involved in various steps of RNA biogenesis and metabolism had antiviral effects. We are now characterizing the antiviral activity of these factors and their role in small RNA silencing. Funded by RO1AI074951 to SC.