RT Journal Article
SR Electronic
T1 Human immunodeficiency virus type 1 impairs sumoylation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101103
DO 10.26508/lsa.202101103
VO 5
IS 6
A1 Bilgül Mete
A1 Emre Pekbilir
A1 Bilge Nur Bilge
A1 Panagiota Georgiadou
A1 Elif Çelik
A1 Tolga Sutlu
A1 Fehmi Tabak
A1 Umut Sahin
YR 2022
UL https://www.life-science-alliance.org/content/5/6/e202101103.abstract
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.