Insects have evolved a wide range of strategies to combat invading pathogens, including viruses. Genes that encode proteins involved in immune responses often evolve under positive selection due to their co-evolution with pathogens. Insect antiviral defense includes the RNA interference (RNAi) mechanism, which is triggered by recognition of non-self, virally produced, double-stranded RNAs. Indeed, insect RNAi genes (e.g., dicer and argonaute-2 ) are under high selective pressure. Honey bees ( Apis mellifera ) are eusocial insects that respond to viral infections via both sequence specific RNAi and a non-sequence specific dsRNA triggered pathway, which is less well-characterized. A transcriptome-level study of virus-infected and/or dsRNA-treated honey bees revealed increased expression of a novel antiviral gene, GenBank: MF116383 , and in vivo experiments confirmed its antiviral function. Due to in silico annotation and sequence similarity, MF116383 was originally annotated as a probable cyclin-dependent serine/threonine-protein kinase . In this study, we confirmed that MF116383 limits virus infection, and carried out further bioinformatic and phylogenetic analyses to better characterize this important gene—which we renamed bee antiviral protein-1 ( bap1 ). Phylogenetic analysis revealed that bap1 is taxonomically restricted to Hymenoptera and Blatella germanica (the German cockroach) and that the majority of bap1 amino acids are evolving under neutral selection. This is in-line with the results from structural prediction tools that indicate Bap1 is a highly disordered protein, which likely has relaxed structural constraints. Assessment of honey bee gene expression using a weighted gene correlation network analysis revealed that bap1 expression was highly correlated with several immune genes—most notably argonaute-2 . The coexpression of bap1 and argonaute-2 was confirmed in an independent dataset that accounted for the effect of virus abundance. Together, these data demonstrate that bap1 is a taxonomically restricted, rapidly evolving antiviral immune gene. Future work will determine the role of bap1 in limiting replication of other viruses and examine the signal cascade responsible for regulating the expression of bap1 and other honey bee antiviral defense genes, including coexpressed ago-2 , and determine whether the virus limiting function of bap1 acts in parallel or in tandem with RNAi.
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The Interplay Between Viruses and RNAi Pathways in Insects
As an overarching immune mechanism, RNA interference (RNAi) displays pathogen specificity and memory via different pathways. The small interfering RNA (siRNA) pathway is the primary antiviral defense mechanism against RNA viruses of insects and plays a lesser role in defense against DNA viruses. Reflecting the pivotal role of the siRNA pathway in virus selection, different virus families have independently evolved unique strategies to counter this host response, including protein-mediated, decoy RNA–based, and microRNA-based strategies. In this review, we outline the interplay between insect viruses and the different pathways of the RNAi antiviral response; describe practical application of these interactions for improved expression systems and for pest and disease management; and highlight research avenues for advancement of the field.
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- Award ID(s):
- 1821914
- PAR ID:
- 10222834
- Date Published:
- Journal Name:
- Annual Review of Entomology
- Volume:
- 66
- Issue:
- 1
- ISSN:
- 0066-4170
- Page Range / eLocation ID:
- 61 to 79
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1146/annurev-ento-033020-090410
