A new mechanism of SAMHD1 inhibition of HIV-1 infection by induction of autophagy. (August 2022)

• Record Type: Journal Article
• Authors: Gao, Chuanhua; Su, Xing; Wu, Nanping; Jin, Changzhong
• Is Part Of: Medical hypotheses. Volume 165(2022)
• Publication Date: 2022-08
• Subjects: dNTP deoxynucleoside triphosphate -- HIV human immunodeficiency virus -- SAMHD1 Sterile alpha motif and histidine/aspartic domain-containing protein 1 -- dGTP diguanosine triphosphate -- NRTIs nucleoside reverse transcriptase inhibitors -- MDMs monocyte-derived macrophages -- AZT zidovudine -- ABC abacavir -- DDC 2′, 3′-dideoxycytidine -- TDF tenofovir disoproxil fumarate -- VLPs virus-like particles -- RNR ribonucleoside reductase -- cART combination antiretroviral therapy; SAMHD1 -- HIV-1 -- Autophagy -- dNTP -- NRTIs; Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Medicine; Periodicals; 610
• DOI: 10.1016/j.mehy.2022.110890
• Languages: English
• ISSNs: 0306-9877

Abstract

Abstract: Sterile alpha motif and histidine/aspartic domain-containing protein 1 (SAMHD1) can inhibit human immunodeficiency virus (HIV)-1 replication by reducing the intracellular deoxynucleoside triphosphate (dNTP) pool and enhance the antiviral potency of nucleoside reverse transcriptase inhibitors (NRTIs) in myeloid cells. NRTIs work well in activated CD4+ T cells with high dNTP concentrations but fail in SAMHD1(-/-) myeloid cells with lower dNTP concentrations. The reason for the poor performance of NRTIs in SAMHD1(-/-) myeloid cells is unclear. We hypothesize that the low dNTP pool in myeloid cells caused by SAMHD1 phosphohydrolase activity can induce autophagy to inhibit HIV-1 infection, but activated CD4+ T cells do not have such autophagy because of the high concentration of intracellular dNTPs. Our hypothesis is supported by two findings: dNTP deficiency can induce autophagy and autophagy can inhibit HIV-1 infection. The importance of our hypothesis is not limited to the inhibition of HIV-1 infection; it is also of great importance to other viral infections, the immune response, and cancer biology.