P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster

• Published in: PLoS pathogens Vol. 9; no. 2; p. e1003137
• Main Authors: Liu, Bo, Behura, Susanta K, Clem, Rollie J, Schneemann, Anette, Becnel, James, Severson, David W, Zhou, Lei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2013; Public Library of Science (PLoS)
• Subjects: Aedes - immunology; Aedes - virology; Animals; Apoptosis; Apoptosis Regulatory Proteins - genetics; Baculoviridae - physiology; Biology; Cells; Cells, Cultured; Disease transmission; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - immunology; Drosophila melanogaster - physiology; Drosophila melanogaster - virology; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Epigenesis, Genetic; Female; Gene Expression Regulation, Viral; Genetic aspects; Genetic vectors; Health aspects; Host-parasite relationships; Immunity, Innate; Infections; Insect Vectors - immunology; Insect Vectors - virology; Insects; Larva; Models, Biological; Neuropeptides - genetics; Nodaviridae - physiology; Physiological aspects; Proteins; RNA, Viral - genetics; Sequence Deletion; Spodoptera - immunology; Spodoptera - virology; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Viral infections; United States; Drosophila Proteins; Sequence Deletion; Insect Vectors; Epigenesis, Genetic; Cells, Cultured; Neuropeptides; Immunity, Innate; Aedes; Spodoptera; Animals; Apoptosis Regulatory Proteins; Tumor Suppressor Protein p53; Baculoviridae; Larva; Gene Expression Regulation, Viral; Models, Biological; RNA, Viral; Nodaviridae; Female; Drosophila melanogaster; Apoptosis
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003137

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.