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Review
. 2020 Apr 28;9(5):1090.
doi: 10.3390/cells9051090.

Modulation of mTORC1 Signaling Pathway by HIV-1

Burkitkan Akbay  1   2 , Anna Shmakova  1   2 , Yegor Vassetzky  1   2   3 , Svetlana Dokudovskaya  1   2
Affiliations
Review

Modulation of mTORC1 Signaling Pathway by HIV-1

Burkitkan Akbay et al. Cells. .

Abstract

Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of cellular proliferation and survival which controls cellular response to different stresses, including viral infection. HIV-1 interferes with the mTORC1 pathway at every stage of infection. At the same time, the host cells rely on the mTORC1 pathway and autophagy to fight against virus replication and transmission. In this review, we will provide the most up-to-date picture of the role of the mTORC1 pathway in the HIV-1 life cycle, latency and HIV-related diseases. We will also provide an overview of recent trends in the targeting of the mTORC1 pathway as a promising strategy for HIV-1 eradication.

Keywords: HIV-1; HIV-1 related diseases; autophagy; mTORC1 pathway.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Upstream and downstream mTORC1 signaling. mTORC1 can be stimulated by various cues. Amino acids activate mTORC1 through GATOR1/GATOR2 complexes and RAGs. Growth factors recruits PI3K to the plasma membrane, which results in subsequent AKT activation. AKT can stimulate mTORC1 either directly through the phosphorylation of its component PRAS40, or via phosphorylation and inhibition of TSC1 from the TSC complex, which leads to RHEB and mTORC1 activations. Under hypoxic condition, mTORC1 is repressed due to TSC activation via AMPK. TSC can also be stimulated (i.e., mTORC1 repressed) via p53 pathway during DNA damage. Viruses can activate mTORC1, especially at the late stage of infection, both upstream, via PI3K/AKT, or acting on downstream mTORC1 target 4E-BP1.
Figure 2
Figure 2
Implication of various HIV-1 proteins in the modulation of autophagy in different cells.
Figure 3
Figure 3
mTORC1 status in HIV-1-related diseases.
See this image and copyright information in PMC

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