title: P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster.
abstract: Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress-responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection.
authors: Department of Molecular Genetics and Microbiology & UF Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors: Bo
authors: B
authors: Liu
authors: Susanta K
authors: SK
authors: Behura
authors: Rollie J
authors: RJ
authors: Clem
authors: Anette
authors: A
authors: Schneemann
authors: James
authors: J
authors: Becnel
authors: David W
authors: DW
authors: Severson
authors: Lei
authors: L
authors: Zhou
mesh_terms: D000330:Aedes / Q000276:immunology / Q000821:virology; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D016367:Baculoviridae / Q000502:physiology*; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000502:physiology / Q000821:virology; D044127:Epigenesis, Genetic; D005260:Female; D015967:Gene Expression Regulation, Viral; D007113:Immunity, Innate; D007303:Insect Vectors / Q000276:immunology / Q000821:virology; D007814:Larva; D008954:Models, Biological; D009479:Neuropeptides / Q000235:genetics; D030381:Nodaviridae / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics; D017384:Sequence Deletion; D018411:Spodoptera / Q000276:immunology / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D009479:Neuropeptides; D012367:RNA, Viral; D016159:Tumor Suppressor Protein p53; C474203:p53 protein, Drosophila; C086973:rpr protein, Drosophila