PT  - JOURNAL ARTICLE
AU  - Bilgül Mete
AU  - Emre Pekbilir
AU  - Bilge Nur Bilge
AU  - Panagiota Georgiadou
AU  - Elif Çelik
AU  - Tolga Sutlu
AU  - Fehmi Tabak
AU  - Umut Sahin
TI  - Human immunodeficiency virus type 1 impairs sumoylation
AID  - 10.26508/lsa.202101103
DP  - 2022 Jun 01
TA  - Life Science Alliance
PG  - e202101103
VI  - 5
IP  - 6
4099  - https://www.life-science-alliance.org/content/5/6/e202101103.short
4100  - https://www.life-science-alliance.org/content/5/6/e202101103.full
SO  - Life Sci. Alliance2022 Jun 01; 5
AB  - 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.