Name
Rotavirus enslaves SUMOylation machinery in parallel to the selective sequestration of nuclear SUMO hotspot PML-NB components within the cytoplasm.
Presenter
Pritam Chandra, National Institute of Cholera and Enteric Diseases
Co-Author(s)
1Pritam Chandra, 1Swassata Kandar, 1Mamta Chawla-Sarkar#
1 Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, India
# chawlam70@gmail.com; chawlasarkar.m@icmr.gov.in
Abstract Category
Cell Biology of Viral Infection
Abstract
Background: The replication and persistence of viruses depend on the balance between the host's antiviral response and the virus's ability to exploit host pathways. While rotavirus replicates in the cytoplasm and does not have proteins entering the nucleus, it still utilizes SUMOylation for its replication, as several viral proteins are SUMOylated. Key SUMO proteins like PML-IV and Daxx regulate viral infection, and studying their role in rotavirus could offer valuable insights.
Method: RV-SA11 strain infection in RV permissive MA104 cells, Immunofluorescence, Transient transfection, His-tag affinity purification and Western blotting.
Result: The study confirmed that several rotaviral proteins are SUMOylated during rotavirus (RV) infection, resulting a subtle change in global SUMOylation. Immunofluorescence and western blot analyses revealed relocation of the SUMO machinery (Ubc9, SUMO-1, and SUMO-2/3) from the nucleus to the cytoplasm, increasing cytosolic SUMOylation while decreasing nuclear SUMOylation. RV infection also disrupts PML nuclear bodies (PML-NBs) thus PML no longer interacts with Daxx. Notably, both PML-IV and Daxx move out of the nucleus, having opposing effects: PML-IV inhibits RV replication through early SUMO conjugation that later declines, while Daxx promotes replication via progressive de-SUMOylation.
Conclusion: RV mediated SUMOylation likely restricts the PML-NB components from accessing SUMO resulting in PML-NB disruption. This disruption may enable RV to influence PML and Daxx; however, not all PML components exit the nucleus. By inducing the translocation of these proteins, RV undermines PML-IV's antiviral defenses and utilizes Daxx for replication. The study highlights the exploitation of post-translational machinery by viruses to facilitate their replication.
Method: RV-SA11 strain infection in RV permissive MA104 cells, Immunofluorescence, Transient transfection, His-tag affinity purification and Western blotting.
Result: The study confirmed that several rotaviral proteins are SUMOylated during rotavirus (RV) infection, resulting a subtle change in global SUMOylation. Immunofluorescence and western blot analyses revealed relocation of the SUMO machinery (Ubc9, SUMO-1, and SUMO-2/3) from the nucleus to the cytoplasm, increasing cytosolic SUMOylation while decreasing nuclear SUMOylation. RV infection also disrupts PML nuclear bodies (PML-NBs) thus PML no longer interacts with Daxx. Notably, both PML-IV and Daxx move out of the nucleus, having opposing effects: PML-IV inhibits RV replication through early SUMO conjugation that later declines, while Daxx promotes replication via progressive de-SUMOylation.
Conclusion: RV mediated SUMOylation likely restricts the PML-NB components from accessing SUMO resulting in PML-NB disruption. This disruption may enable RV to influence PML and Daxx; however, not all PML components exit the nucleus. By inducing the translocation of these proteins, RV undermines PML-IV's antiviral defenses and utilizes Daxx for replication. The study highlights the exploitation of post-translational machinery by viruses to facilitate their replication.