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

• Published in: Virology journal 2012-11, Vol.9 (1), p.277-277, Article 277
• Main Authors: Emeagwali, Nkiruka, Hildreth, James E K
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; Amino acids; Cell division; DNA; DNA repair; DNA, Viral - genetics; DNA, Viral - metabolism; Gene Expression Regulation, Viral; Genetic diversity; Genetic transcription; Genomes; Genomics; HEK293 Cells; HIV; HIV (Viruses); HIV Infections - virology; HIV Integrase - genetics; HIV Integrase - metabolism; HIV-1; HIV-1 - genetics; HIV-1 - metabolism; HIV-1 - physiology; HIV-1 transcription Twik-related Acid Sensitive K+ proteins; Homology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human Immunodeficiency Virus Proteins - genetics; Human Immunodeficiency Virus Proteins - metabolism; Humans; Ion channels; Ion Channels - metabolism; Jurkat Cells; Lymphoid tissue; Medical research; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; NF- Kappa B protein; Potassium; Potassium channels; Potassium Channels, Tandem Pore Domain - genetics; Potassium Channels, Tandem Pore Domain - metabolism; Proteins; RelA protein; Replication; Transcription; Transcription Factor RelA - genetics; Transcription Factor RelA - metabolism; Transcription, Genetic; Transfection; Transmembrane domains; Unintegrated HIV-1 DNA; Viral protein U; Viral proteins; Viral Regulatory and Accessory Proteins - genetics; Viral Regulatory and Accessory Proteins - metabolism; Virus Integration; Virus Replication
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-9-277

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. 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). 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.