Human immunodeficiency virus type 1 impairs sumoylation

Life Sci Alliance. 2022 Feb 18;5(6):e202101103. doi: 10.26508/lsa.202101103. Print 2022 Jun.

Abstract

During infection, the human immunodeficiency virus type 1 (HIV-1) manipulates host cell mechanisms to its advantage, thereby controlling its replication or latency, and evading immune responses. Sumoylation is an essential post-translational modification that controls vital cellular activities including proliferation, stemness, or anti-viral immunity. SUMO peptides oppose pathogen replication and mediate interferon-dependent anti-viral activities. In turn, several viruses and bacteria attack sumoylation to disarm host immune responses. Here, we show that HIV-1 impairs cellular sumoylation and targets the host SUMO E1-activating enzyme. HIV-1 expression in cultured HEK293 cells or in CD4+ Jurkat T lymphocytes diminishes sumoylation by both SUMO paralogs, SUMO1 and SUMO2/3. HIV-1 causes a sharp and specific decline in UBA2 protein levels, a subunit of the heterodimeric SUMO E1 enzyme, which likely serves to reduce the efficiency of global protein sumoylation. Furthermore, HIV-1-infected individuals display a significant reduction in total leukocyte sumoylation that is uncoupled from HIV-induced cytopenia. Because sumoylation is vital for immune function, T-cell expansion and activity, loss of sumoylation during HIV disease may contribute to immune system deterioration in patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HEK293 Cells
  • HIV Infections*
  • HIV-1*
  • Humans
  • Protein Processing, Post-Translational
  • Sumoylation
  • Ubiquitin-Activating Enzymes

Substances

  • UBA2 protein, human
  • Ubiquitin-Activating Enzymes