title: The efficiency of Vpx-mediated SAMHD1 antagonism does not correlate with the potency of viral control in HIV-2-infected individuals.
abstract: BACKGROUND
  The presence of a vpx gene distinguishes HIV-2 from HIV-1, the main causative agent of AIDS. Vpx degrades the restriction factor SAMHD1 to boost HIV-2 infection of macrophages and dendritic cells and it has been suggested that the activation of antiviral innate immune responses after Vpx-dependent infection of myeloid cells may explain why most HIV-2-infected individuals efficiently control viral replication and become long-term survivors. However, the role of Vpx-mediated SAMHD1 antagonism in the virological and clinical outcome of HIV-2 infection remained to be investigated.
  
  
  RESULTS
  Here, we analyzed the anti-SAMHD1 activity of vpx alleles derived from seven viremic and four long-term aviremic HIV-2-infected individuals. We found that effective Vpx-mediated SAMHD1 degradation and enhancement of myeloid cell infection was preserved in most HIV-2-infected individuals including all seven that failed to control the virus and developed AIDS. The only exception were vpx alleles from an aviremic individual that predicted a M68K change in a highly conserved nuclear localization signal which disrupted the ability of Vpx to counteract SAMHD1. We also found that HIV-2 is less effective than HIV-1 in inducing innate immune activation in dendritic cells.
  
  
  CONCLUSIONS
  Effective immune control of viral replication in HIV-2-infected individuals is not associated with increased Vpx-mediated degradation of SAMHD1.
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Ulm 89081, Germany.
authors.forename: Hangxing
authors.initials: H
authors.lastname: Yu
authors.forename: Shariq M
authors.initials: SM
authors.lastname: Usmani
authors.forename: Alexandra
authors.initials: A
authors.lastname: Borch
authors.forename: Julia
authors.initials: J
authors.lastname: Krämer
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stürzel
authors.forename: Mohammad
authors.initials: M
authors.lastname: Khalid
authors.forename: Xuehua
authors.initials: X
authors.lastname: Li
authors.forename: Daniela
authors.initials: D
authors.lastname: Krnavek
authors.forename: Marchina E
authors.initials: ME
authors.lastname: van der Ende
authors.forename: Albert D
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Rob A
authors.initials: RA
authors.lastname: Gruters
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D016000:Cluster Analysis; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000821:virology; D015498:HIV-2 / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D010802:Phylogeny; D059748:Proteolysis; D000076106:SAM Domain and HD Domain-Containing Protein 1; D017422:Sequence Analysis, DNA; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: C074286:VPX protein, Human immunodeficiency virus 2; D054334:Viral Regulatory and Accessory Proteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins