Division of Infectious Diseases and Immunology, Department of Medicine; RNA Therapeutics Institute
Amino Acids, Peptides, and Proteins | Bacterial Infections and Mycoses | Immunity | Immunology of Infectious Disease | Immunopathology | Virology | Virus Diseases | Viruses
The host immune response and virus-encoded immune evasion proteins pose constant, mutual selective pressure on each other. Virally encoded immune evasion proteins also indicate which host pathways must be inhibited to allow for viral replication. Here, we show that IIV-6 is capable of inhibiting the two Drosophila NF-kappaB signaling pathways, Imd and Toll. Antimicrobial peptide (AMP) gene induction downstream of either pathway is suppressed when cells infected with IIV-6 are also stimulated with Toll or Imd ligands. We find that cleavage of both Imd and Relish, as well as Relish nuclear translocation, three key points in Imd signal transduction, occur in IIV-6 infected cells, indicating that the mechanism of viral inhibition is farther downstream, at the level of Relish promoter binding or transcriptional activation. Additionally, flies co-infected with both IIV-6 and the Gram-negative bacterium, Erwinia carotovora carotovora, succumb to infection more rapidly than flies singly infected with either the virus or the bacterium. These findings demonstrate how pre-existing infections can have a dramatic and negative effect on secondary infections, and establish a Drosophila model to study confection susceptibility.
DNA virus, IIV-6; Imd, NF-κB, host-pathogen interactions, immunomodulators, viral immune evasion
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© 2019 by the authors. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
DOI of Published Version
Viruses. 2019 May 1;11(5). pii: v11050409. doi: 10.3390/v11050409. Link to article on publisher's site
West, Cara C.; Rus, Florentina; Chen, Ying; Kleino, Anni; Gangloff, Monique; Gammon, Don B.; and Silverman, Neal S., "IIV-6 Inhibits NF-kappaB Responses in Drosophila" (2019). Open Access Articles. 3866.
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This work is licensed under a Creative Commons Attribution 4.0 License.
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