Location: Mosquito and Fly ResearchTitle: P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster Author
Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/3/2013
Publication Date: 2/7/2013
Citation: Liu, B., Behura, S.K., Clem, R.J., Schneemann, A., Becnel, J.J., Severson, D., Zhou, L. 2013. P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster. PLoS Pathogens. 9(2):1-12. Interpretive Summary: Mosquitoes are important vectors of diseases to man and animals and new control strategies are being investigated by ARS scientists. One group of new microbial control agents under investigation are mosquito pathogenic viruses. Understanding the interactions between these viruses and the mosquito host are crucial to further development. In this collaborative research project between ARS and University of Florida researchers, the response of mosquitoes and Drosophila response to attack by a killer virus was investigated. It was discovered that a defensive pathway that involved programmed cell death was activated in response to viral infection but was blocked by the virus (mechanism unknown) in susceptible hosts but not in non-susceptible mosquitoes. Understanding the pathways involved in mosquito defensive response to viral infection and the means to block these responses can provide important clues to pathogenic virus host range as well as vector compatibility to other types of viruses in mosquitoes.
Technical 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.