Abstract
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-κB 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.
Highlights
The host immune system and the viruses that challenge it face constant, mutual, selective pressure for survival
After 6 h of Iridescent Virus-6 (IIV-6) infection, cells were stimulated with 2 μg/mL of PGN for an additional 6 h, and gene expression analyzed by qRT-PCR
Inhibition we focused on the Imd pathway to Relish tease apart the mechanism of NF-κB inhibition by IIV-6
Summary
The host immune system and the viruses that challenge it face constant, mutual, selective pressure for survival. This perpetual arms race, known as the Red Queen Hypothesis [1], has created a plethora of mechanisms that the cell uses to thwart viral replication, and a plethora of novel immune evasion tactics that viruses use to evade the immune response, in some cases even stealing genes from their hosts to suit this purpose [2]. The model poxvirus Vaccinia encodes a variety NF-κB pathway inhibitors, and a recently identified invertebrate DNA virus, Kallithea virus, is able to inhibit Drosophila Toll signaling [3,4]. The interplay between the virus and host, which pathways the virus devotes its resources to inhibit, provides insight as to which defense mechanisms
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
