Human immunodeficiency virus type 1 Vpu and cellular TASK proteins suppress transcription of unintegrated HIV-1 DNA

Nkiruka Emeagwali, James Hildreth

Research output: Contribution to journalArticle

3 Scopus citations

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). Conclusion: 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.

Original languageEnglish (US)
Article number277
JournalVirology Journal
Volume9
DOIs
StatePublished - 2012

Keywords

  • HIV-1
  • HIV-1 transcription Twik-related Acid Sensitive K+ proteins
  • Unintegrated HIV-1 DNA
  • Viral protein U

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Medicine(all)

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