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In Vitro SUMOylation Assay to Study SUMO E3 Ligase Activity
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Published on: January 29, 2018

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Human immunodeficiency virus type 1 impairs sumoylation.

Bilgül Mete1, Emre Pekbilir2, Bilge Nur Bilge3

  • 1Department of Infectious Diseases and Clinical Microbiology, Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Istanbul, Turkey.

Life Science Alliance
|February 19, 2022
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Summary

Human immunodeficiency virus type 1 (HIV-1) impairs cellular sumoylation, a key process for immune function, by targeting the SUMO E1 enzyme. This disruption may contribute to immune deterioration in HIV-infected individuals.

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Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Human immunodeficiency virus type 1 (HIV-1) manipulates host cell processes for replication and immune evasion.
  • Sumoylation is a crucial post-translational modification regulating cellular activities, including anti-viral immunity.
  • Viruses often target host sumoylation pathways to disarm immune responses.

Purpose of the Study:

  • To investigate whether HIV-1 affects cellular sumoylation.
  • To identify the specific mechanisms by which HIV-1 might interfere with sumoylation.
  • To determine the impact of HIV-1 infection on sumoylation levels in patients.

Main Methods:

  • Assessing sumoylation levels in HEK293 cells and CD4+ Jurkat T lymphocytes expressing HIV-1.
  • Quantifying protein levels of UBA2, a subunit of the SUMO E1-activating enzyme.
  • Measuring total leukocyte sumoylation in HIV-1-infected individuals.

Main Results:

  • HIV-1 expression significantly diminishes sumoylation mediated by both SUMO1 and SUMO2/3.
  • HIV-1 infection leads to a specific and substantial decrease in UBA2 protein levels.
  • HIV-1-infected individuals exhibit reduced leukocyte sumoylation, independent of cytopenia.

Conclusions:

  • HIV-1 actively impairs cellular sumoylation by targeting the SUMO E1-activating enzyme (UBA2).
  • The reduction in sumoylation may compromise immune function, T-cell activity, and expansion.
  • Loss of sumoylation during HIV disease could be a contributing factor to immune system deterioration.