Short-term persistence precedes pathogenic infection: Infection kinetics of cricket paralysis virus in silkworm-derived Bm5 cells

Abstract

Next generation sequencing has revealed the widespread occurrence of persistent virus infections in insects but little is known regarding to what extent persistent infections can affect cellular physiology and how they might contribute to the development of disease. In contrast to the pathogenic infections occurring in Drosophila S2 cells, it was observed that Cricket Paralysis virus (CrPV; Dicistroviridae) causes persistent infections in 9 lepidopteran and 2 coleopteran cell lines. The status of the persistent infection was subsequently investigated in more detail using silkworm-derived Bm5 cells, where the infection eventually becomes pathogenic after 3-4 weeks. The short-term persistence period in Bm5 cells is characterized by low levels of viral replication and virion production as well as by the production of viral siRNAs. However, during this period cellular physiology also becomes altered since the cells become susceptible to infection by the nodavirus Flock House virus (FHV). Pathogenicity and widespread mortality at 4 weeks is preceded by a large increase in virion production and the transcriptional activation of immune-related genes encoding RNAi factors and transcription factors in the Toll, Imd and Jak-STAT pathways. During the infection of Bm5 cells, the infective properties of CrPV are not altered, indicating changes in the physiology of the host cells during the transition from short-term persistence to pathogenicity. The in vitro system of Bm5 cells persistently infected with CrPV can therefore be presented as an easily accessible model to study the nature of persistent virus infections and the processes that trigger the transition to pathogenicity, for instance through the application of different "omics" approaches (transcriptomics, proteomics, metabolomics). The different factors that can cause the transition from persistence to pathogenicity in the Bm5-CrPV infection model are discussed.

Keywords: Antiviral immune response; Bm5 cells; Cricket paralysis virus; Host susceptibility; Pathogenicity; Persistent infection; RNAi.