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Open Access Research

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

Nkiruka Emeagwali1 and James EK Hildreth2*

Author Affiliations

1 Center for AIDS Health Disparities Research, Meharry Medical College, Nashville, TN, 37208, USA

2 Department of Molecular and Cellular Biology, College of Biological Sciences, University of California, Davis, One Shields Ave, Davis, CA, 95616, USA

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Virology Journal 2012, 9:277  doi:10.1186/1743-422X-9-277

Published: 19 November 2012

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.

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