Dengue virus NS5 polymerase counteracts PML-mediated intrinsic immunity

MONTE, MARTIN; LADELFA, MARÍA FATIMA; CYBELE C. GARCÍA; FEDERICO GIOVANNONI; PETER HEMMERICH

Glasgow

Congreso; FEMS 2019 8th Congress of European Microbiologists; 2019

Federation of European Microbiologists (FEMS)

Background: Dengue fever, caused by dengue virus (DENV) infection, is an important public health problem threatening 40% of the world?s population. Currently there is no antiviral therapy against DENV; its development requires a better understanding of virus-host interactions and antiviral immunity. Besides innate and adaptive immunity, intrinsic immunity in individual cells plays a key role in the control of viral infections. Intrinsic immunity depends on cellular proteins that block viral replication at any stage of the virus life cycle. Promyelocytic leukemia (PML) protein contributes to intrinsic immunity against many viruses and is the key organizer of nuclear bodies (PML-NBs), which are discrete structures within the nucleus of mammalian cells. There is increasing evidence involving PML as a DNA virus antiviral factor, but less information is available regarding the role of PML against RNA viruses, including DENV.Objectives: Characterize the role of PML as a mediator of intrinsic immunity against DENV.Methods: A549 cells and the four different serotypes of DENV were used throughout the study.Results: By performing knock-down and overexpression studies, we demonstrated that PML displays antiviral activity against DENV. We showed that, in infected cells, PML-NBs are disassembled after DENV infection and we proved that the DENV polymerase (non-structural protein 5, NS5) interacts with PML to disrupt PML-NBs and counteract PML-mediated intrinsic immunity. These data are expected to contribute to the understanding of the biological principles underlying DENV strategy to evade the host antiviral response.