Induction and suppression of NF-_kB signalling by a DNA virus ofDrosophila

Abstract

Interactions between the insect immune system and RNA viruses have been best studied in Drosophila, where RNA interference, NF-κB and JAK-STAT pathways underlie antiviral immunity. In response to these immune mechanisms, insect viruses have convergently evolved suppressors of RNA interference that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because few Drosophila-infecting DNA virus isolates are available. Here, we use a recently-isolated DNA virus of Drosophila melanogaster, Kallithea virus, to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We find that fly mutants for RNA interference and Immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identify the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, strongly suggesting that Toll mediates antiviral responses during Kallithea virus infection, but that it is suppressed by the virus. Further, we find that Kallithea gp83 inhibits Toll signalling either through NF-κB transcription factor regulation, or transcriptionally. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in a Drosophila virus, extending the known diversity of insect virus-encoded immune inhibitors.

Antimicrobial Peptides as Potential Antiviral Factors in Insect Antiviral Immune Response

“…On the other hand, it should be kept in mind that the interaction between host and virus is a complex process in which the immune response of the host is counteracted by the immune escape mechanisms of the virus. A recent study found that Kallithea virus (DNA virus of D. melanogaster ) gp83 inhibits Toll signaling through the regulation of NF-κB transcription factors ( 25 ). The immunosuppression by Kallithea virus infection is also accompanied by the general down-regulation of AMP gene expression ( 25 ).…”

“…A recent study found that Kallithea virus (DNA virus of D. melanogaster ) gp83 inhibits Toll signaling through the regulation of NF-κB transcription factors ( 25 ). The immunosuppression by Kallithea virus infection is also accompanied by the general down-regulation of AMP gene expression ( 25 ). Because the action of AMPs may be neutralized by the virus, simple tests cannot decide or exclude whether AMPs have antiviral activity.…”

The discovery, distribution and diversity of DNA viruses associated withDrosophila melanogasterin Europe

“…Kallithea virus has been isolated for experimental study, and reduces male longevity and female fecundity (Palmer et al 2018). Consistent with its presumed niche as a natural pathogen of Drosophila, Kallithea virus encodes a suppressor of D. melanogaster NF-kappa B immune signalling (Palmer et al 2019). Prior to the work described here, the only other reported natural DNA virus infection of a drosophilid was the discovery (again through metagenomic sequencing) of a small number of RNA reads from Invertebrate iridescent virus 31 (IIV31; Armadillidium vulgare iridescent virus) in D. immigrans and D. obscura (Webster et al 2016).…”

“…2018). Consistent with its presumed niche as a natural pathogen of Drosophila , this virus encodes a suppressor of D. melanogaster NF-kappa B immune signalling (Palmer et al . 2019).…”

“…The lack of native DNA viruses for D. melanogaster has practical implications for research, as the majority of experiments have had to utilise viruses that do not naturally infect Drosophila , and which have not co-evolved with them (Bronkhorst et al . 2014, West and Silverman 2018, but see Palmer et al . 2019).…”