HIV p17 enhances T cell proliferation by suppressing autophagy through the p17-OLA1-GSK3β axis under nutrient starvation.
Nutrient starvation is a common phenomenon that occurs during T cell activation. Upon pathogen infection, large amounts of immune cells migrate to infection sites, and antigen-specific T cells are activated; this is followed by rapid proliferation through clonal expansion. The dramatic expansion of cells will commonly lead to nutrient shortage. Cellular autophagy is often upregulated as a way to sustain the body's energy requirements. During infection, human immunodeficiency virus (HIV) co-opts a series of host cell metabolic pathways for replication. Several HIV proteins, such as Env, Nef, and Vpr, have already been reported as being involved in autophagy-related processes. In this report, we identified that the HIV p17 protein acts as a major factor in suppressing the autophagic process in T cells, especially under glucose starvation condition. HIV p17 interacts with Obg-like ATPase 1 (OLA1) and disrupts OLA1-glycogen synthase kinase-3 beta (GSK3β) complex, leading to GSK3β hyperactivation. Consequently, a prior proliferation of HIV-infected T cells under glucose starvation will occur. The inhibition of autophagy also aids HIV replication by antagonizing the antiviral effect of autophagy. Our study shows a new cellular pathway that HIV can hijack for viral spreading by a prior proliferation of HIV-loaded T cells and may provide new therapeutic targets for acquired immunodeficiency syndrome intervention.
['Lu|Jing|J|0000-0001-6741-6850', 'Jia|Jiayuan|J|', 'Zhang|Jiahui|J|', 'Liu|Xinqi|X|']
D000251:Adenosine Triphosphatases D001343:Autophagy D049109:Cell Proliferation D019204:GTP-Binding Proteins D005947:Glucose D000071679:Glycogen Synthase Kinase 3 beta D057809:HEK293 Cells D015488:HIV Antigens D015497:HIV-1 D006367:HeLa Cells D000076662:Host Microbial Interactions D006801:Humans D019169:Jurkat Cells D008213:Lymphocyte Activation D013217:Starvation D013601:T-Lymphocytes D054301:gag Gene Products, Human Immunodeficiency Virus
HIV autophagy T cell survival protein interaction viral infection