2016
DOI: 10.1016/j.bcp.2016.02.002
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Dasatinib inhibits HIV-1 replication through the interference of SAMHD1 phosphorylation in CD4+ T cells

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Cited by 54 publications
(64 citation statements)
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References 89 publications
(64 reference statements)
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“…In addition to its role in regulating genome stability, SAMHD1 is best known for its ability to block infection of a broad range of retroviruses including human immunodeficiency virus type 1 (HIV-1). During viral infection, SAMHD1 depletes the cellular dNTPs needed for reverse transcription of the viral RNA genome (2)(3)(4)(5)(6)(7)(8). In the cell, SAMHD1 activity is modulated by allosteric activation and phosphorylation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”
Section: Introductionmentioning
confidence: 99%
“…In addition to its role in regulating genome stability, SAMHD1 is best known for its ability to block infection of a broad range of retroviruses including human immunodeficiency virus type 1 (HIV-1). During viral infection, SAMHD1 depletes the cellular dNTPs needed for reverse transcription of the viral RNA genome (2)(3)(4)(5)(6)(7)(8). In the cell, SAMHD1 activity is modulated by allosteric activation and phosphorylation (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”
Section: Introductionmentioning
confidence: 99%
“…In 2014, Pogliaghi et al reported the reduction of HIV replication induced by dasatinib in vitro and suggested that this was mediated by the inhibition of activation and proliferation [13]. More recently, it has been shown that dasatinib is able to inhibit SAMHD1 phosphorylation in CD4 + T cells [14]. SAMHD1 is a cellular factor that acts as an innate antiviral restriction factor, and whose phosphorylation (that leads to inactivation) is induced by HIV.…”
Section: Tyrosine Kinase Inhibitors and Hiv-1mentioning
confidence: 99%
“…So far, in vitro and ex vivo results suggest that dasatinib is the most potent anti-HIV drug among the TKI family [14] in CD4T cells, without cell toxicity. Consequently, this drug should be chosen to be tested in pilot clinical trials.…”
Section: Tyrosine Kinase Inhibitors and Hiv-1mentioning
confidence: 99%
“…Although mSAMHD1 and hSAMHD1 are highly similar in sequence and function, we found that mSAMHD1 possesses a more complex nucleotide-induced activation process, highlighting the regulatory role of the SAM domain. Our results provide new insights into the regulation of SAMHD1 activity, thereby will facilitate the improvement of HIV mouse models and the development of new therapies for certain cancers and autoimmune diseases.3The sterile alpha-motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a dNTP phosphohydrolase that restricts viral replication by limiting the cellular dNTP pool [1][2][3][4][5][6][7] . Without an adequate supply of dNTPs, retroviruses like HIV-1 cannot complete reverse transcription.…”
mentioning
confidence: 99%
“…The sterile alpha-motif (SAM) and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a dNTP phosphohydrolase that restricts viral replication by limiting the cellular dNTP pool [1][2][3][4][5][6][7] . Without an adequate supply of dNTPs, retroviruses like HIV-1 cannot complete reverse transcription.…”
mentioning
confidence: 99%