Research Summary

Understanding the role of RNAi-mediated antiviral host defense against DNA viruses

Insects lack adaptive immunity yet can combat viral infection most effectively. Recently, it has become evident that RNA interference (RNAi) plays a key role in antiviral defense mechanism in insects. RNAi is a small non-coding RNA-mediated post-transcriptional gene silencing mechanism. In insects, our knowledge about RNAi-mediated antiviral defense is mainly confined to RNA viruses. DNA viruses have hardly been the subjects of such investigations, except for few recent reports. To comprehend the role of RNAi in antiviral defense against DNA viruses, we have selected an insect-virus model system comprising the domesticated silkworm, Bombyx mori, and its natural pathogen, Bombyx mori nucleopolyhedrosis virus (BmNPV), which is a double-stranded DNA virus. Different strains of silkworm display a high degree of variation with regards to their tolerance against BmNPV, which provides a powerful tool to understand viral tropism and evolution of intricate insect-viral interactions. Using this insect-virus model, we are interested in addressing the some of the important questions of antiviral RNAi against DNA viruses such as: What are the key components of RNAi that participate in DNA virus infection? Does RNAi regulate other innate immune responses? Do cellular miRNAs inhibit virus infection by targeting viral transcripts? Can cellular small ncRNA signatures be used as a genetic marker against viral infection?

Figure Legend: Schematic representation of our working model. We have found that when BmNPV infects silkworm, it activates the RNAi machinery components and start encoding viral small RNAs, which not only regulates host genes but also auto-regulate its own mRNA transcripts expression. Besides, we have also observed differential expression of cellular small and long non-coding RNAs upon BmNPV infection. But what we don’t yet complete understood is how host utilizes these differentially expressed RNAs to combat BmNPV attack? Some of the important research questions what we are presently interested in addressing are represented in blue.