title: Human immunodeficiency virus type 1 Vpu and cellular TASK proteins suppress transcription of unintegrated HIV-1 DNA.
abstract: BACKGROUND
  Unintegrated HIV-1 DNA serves as transcriptionally active templates in HIV-infected cells. Several host factors including NF-κβ enhance HIV-1 transcription. HIV-1 induced NF-κβ activation can be suppressed by viral protein U (Vpu). Interestingly HIV-1 Vpu shares amino acid homology with cellular Twik-related Acid Sensitive K+ (TASK) channel 1 and the proteins physically interact in cultured cells and AIDS lymphoid tissue. Furthermore, the first transmembrane domain of TASK-1 is functionally interchangeable with Vpu and like Vpu enhances HIV-1 release.
  
  
  RESULTS
  Here we further characterize the role of TASK channels and Vpu in HIV-1 replication. We demonstrate that both TASK channels and Vpu can preferentially inhibit transcription of unintegrated HIV-1 DNA. Interestingly, TASK-1 ion channel function is not required and suppression of HIV-1 transcription by TASK-1 and Vpu was reversed by overexpression of RelA (NF-κβ p65).
  
  
  CONCLUSIONS
  TASK proteins and Vpu suppress transcription of unintegrated HIV-1 DNA through an NF-κβ-dependent mechanism. Taken together these findings support a possible physiological role for HIV-1 Vpu and TASK proteins as modulators of transcription of unintegrated HIV-1 DNA genomes.
authors.affiliation: Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN 37208, USA.
authors.forename: Nkiruka
authors.initials: N
authors.lastname: Emeagwali
authors.forename: James E K
authors.initials: JE
authors.lastname: Hildreth
mesh_terms: D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D015658:HIV Infections / Q000821:virology; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D019169:Jurkat Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D016662:Virus Integration; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D004279:DNA, Viral; D019427:HIV Integrase; D054298:Human Immunodeficiency Virus Proteins; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D051996:Transcription Factor RelA; D054334:Viral Regulatory and Accessory Proteins; C498143:RELA protein, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins; C420132:potassium channel subfamily K member 3