HIV p17 enhances T cell proliferation by suppressing autophagy through the p17‐OLA1‐GSK3β axis under nutrient starvation

다국어 초록 (Multilingual Abstract)

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.
1）HIV p17 interacts with OLA1 and disrupts OLA1‐GSK3β complex.
2）p17‐OLA1‐GSK3β axis regulates T cell proliferation under glucose starvation.
3）HIV p17 can inhibit cell autophagic process under nutrient limitation.