منابع مشابه
Small Molecule Inhibition of SAMHD1 dNTPase by Tetramer Destabilization
SAMHD1 is a GTP-activated nonspecific dNTP triphosphohydrolase that depletes dNTP pools in resting CD4+ T cells and macrophages and effectively restricts infection by HIV-1. We have designed a nonsubstrate dUTP analogue with a methylene bridge connecting the α phosphate and 5' carbon that potently inhibits SAMHD1. Although pppCH2dU shows apparent competitive inhibition, it acts by a surprising ...
متن کاملPositive selection in the evolution of mammalian interleukin-2 genes.
In vertebrates, there are many secreted regulatory proteins that participate in host defense. Interleukin-2 (IL-2) is one of these proteins, and it is secreted primarily by activated T lymphocytes. Interaction between IL-2 and its receptor on the T cell membrane triggers several signal transduction pathways, resulting in clonal expansion of T cells. While this proliferation-promoting activity i...
متن کاملRestriction of virus infection but not catalytic dNTPase activity is regulated by phosphorylation of SAMHD1.
SAMHD1 is a host protein responsible, at least in part, for the inefficient infection of dendritic, myeloid, and resting T cells by HIV-1. Interestingly, HIV-2 and SIVsm viruses are able to counteract SAMHD1 by targeting it for proteasomal degradation using their Vpx proteins. It has been proposed that SAMHD1 is a dGTP-dependent deoxynucleoside triphosphohydrolase (dNTPase) that restricts HIV-1...
متن کاملTetramerization of SAMHD1 Is Required for Biological Activity and Inhibition of HIV Infection*
SAMHD1 is a dGTP-activated dNTPase that has been implicated as a modulator of the innate immune response. In monocytes and their differentiated derivatives, as well as in quiescent cells, SAMHD1 strongly inhibits HIV-1 infection and, to a lesser extent, HIV-2 and simian immunodeficiency virus (SIV) because of their virion-associated virulence factor Vpx, which directs SAMHD1 for proteasomal deg...
متن کاملRecombination and selection in the evolution of picornaviruses and other Mammalian positive-stranded RNA viruses.
Picornaviridae are a large virus family causing widespread, often pathogenic infections in humans and other mammals. Picornaviruses are genetically and antigenically highly diverse, with evidence for complex evolutionary histories in which recombination plays a major part. To investigate the nature of recombination and selection processes underlying the evolution of serotypes within different p...
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ژورنال
عنوان ژورنال: Proceedings of the National Academy of Sciences
سال: 2019
ISSN: 0027-8424,1091-6490
DOI: 10.1073/pnas.1908755116