title: Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility.
abstract: SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park - Price Center 501, New York, NY 10461, USA.
authors.forename: Tommy E
authors.initials: TE
authors.lastname: White
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park - Price Center 501, New York, NY 10461, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Brandariz-Nuñez
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park - Price Center 501, New York, NY 10461, USA.
authors.forename: Jose Carlos
authors.initials: JC
authors.lastname: Valle-Casuso
authors.affiliation: Department of Microbiology & Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Knowlton
authors.affiliation: Department of Microbiology & Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Baek
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Sawyer
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 1301 Morris Park - Price Center 501, New York, NY 10461, USA. Electronic address: Felipe.Diaz-Griffero@einstein.yu.edu.
authors.forename: Felipe
authors.initials: F
authors.lastname: Diaz-Griffero
mesh_terms: D000818:Animals; D003854:Deoxyribonucleotides / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D015498:HIV-2 / Q000502:physiology*; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000076106:SAM Domain and HD Domain-Containing Protein 1
chemical_list: D003854:Deoxyribonucleotides; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: HIV-1; LINE-1; SAMHD1; SNPs; Vpx; dNTPs