%0 Journal Article %A Bilgül Mete %A Emre Pekbilir %A Bilge Nur Bilge %A Panagiota Georgiadou %A Elif Çelik %A Tolga Sutlu %A Fehmi Tabak %A Umut Sahin %T Human immunodeficiency virus type 1 impairs sumoylation %D 2022 %R 10.26508/lsa.202101103 %J Life Science Alliance %P e202101103 %V 5 %N 6 %X 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. %U https://www.life-science-alliance.org/content/lsa/5/6/e202101103.full.pdf