title: Antagonism of SAMHD1 is actively maintained in natural infections of simian immunodeficiency virus.
abstract: Restriction factors are effectors of the innate immune response to viral pathogens that inhibit viral replication by operating as molecular barriers to steps of the viral life cycle. The restriction factor SAMHD1 blocks lentiviral reverse transcription in myeloid cells and resting CD4+ T cells. Many lineages of lentiviruses, including HIV-2 and other simian immunodeficiency viruses, encode accessory genes that serve to counteract host SAMHD1 restriction by causing degradation of the antiviral factor. The viral accessory protein Vpr is responsible for SAMHD1 degradation in some lineages of lentiviruses, whereas in others the related protein Vpx assumes this task. However, HIV-1 has no SAMHD1 degradation capability, leading to questions about the selective advantage of this activity. We use an evolutionary approach to examine the importance of SAMHD1 antagonism for viral fitness by studying adaptation to host SAMHD1 in natural simian immunodeficiency virus infections of African Green Monkeys. We identified multiple SAMHD1 haplotypes in African Green Monkeys and find that the vpr gene from different strains of Simian Immunodeficiency Virus has adapted to the polymorphisms of the African Green Monkey population in which it is found. Such evidence of viral adaptation to host restriction indicates that SAMHD1 antagonism is actively maintained in natural infections and that this function must be advantageous to viral fitness, despite its absence in HIV-1.
authors: Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195.
authors: Chelsea J
authors: CJ
authors: Spragg
authors: Michael
authors: M
authors: Emerman
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops / Q000276:immunology*; D019143:Evolution, Molecular; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D022423:Myeloid Cells; D000076106:SAM Domain and HD Domain-Containing Protein 1; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014779:Virus Replication / Q000276:immunology*
chemical_list: D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: SIVagm; Vpr; evolution