Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

• Published in: Virology (New York, N.Y.) Vol. 460; pp. 34 - 44
• Main Authors: White, Tommy E, Brandariz-Nuñez, Alberto, Valle-Casuso, Jose Carlos, Knowlton, Caitlin, Kim, Baek, Sawyer, Sara L, Diaz-Griffero, Felipe
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2014
• Subjects: 60 APPLIED LIFE SCIENCES; AIDS VIRUS; AMINO ACIDS; ANEMIAS; Animals; COMPARTMENTS; DENDRITES; Deoxyribonucleotides - metabolism; dNTPs; HIV Infections - genetics; HIV Infections - metabolism; HIV Infections - virology; HIV-1; HIV-1 - physiology; HIV-2 - physiology; HUMAN POPULATIONS; Humans; Infectious Disease; LINE-1; Long Interspersed Nucleotide Elements; MACROPHAGES; Monomeric GTP-Binding Proteins - genetics; NUCLEOTIDES; Polymorphism, Single Nucleotide; PROTEINS; RNA; SAM Domain and HD Domain-Containing Protein 1; SAMHD1; SNPs; Vpx; HIV-1; SNPs; dNTPs; LINE-1; SAMHD1; Vpx
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2014.04.023

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.