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. Author manuscript; available in PMC: 2020 Jul 29.
Published in final edited form as: Cell Rep. 2020 Jun 23;31(12):107810. doi: 10.1016/j.celrep.2020.107810

Figure 7. Summary of Mechanisms by Which the mTOR Pathway Determines Permissivity to HIV-1 by Regulating Cellular Metabolite Pools.

Figure 7.

Activation of the mTORC1 signaling cascade coordinates increases in glucose uptake (via Glut1 induction) and the PPP and c-Myc activities that are each needed for nucleotide biosyntheses. These processes and the c-Myc-dependent increases in ribonucleotide reductase expand the pools of all 4 dNTPs to facilitate HIV-1 reverse transcription (step 1). mTORC1 also increases the transport of glutamine into the cell via the induction of ASCT2 expression, thereby elevating the level of α-KG that enters the TCA cycle for citrate production. Glut1-mediated glucose transport also enhances the entry of another citrate precursor, pyruvate, into the TCA cycle. ATP citrate lyase (ACLY) is also activated by actions of both mTORC1 and mTORC2 and facilitates conversion of the expanded pool of citrate to Ac-CoA. Increased Ac-CoA fuels the acetylation of the α-tubulin that stabilizes microtubules resulting from α-tubulin polymerization, which are used for cytoplasmic trafficking of HIV-1 toward the nucleus (step 2).