Abstract
BackgroundUnintegrated 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.ResultsHere 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).ConclusionTASK 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.
Highlights
Unintegrated Human immunodeficiency virus type 1 (HIV-1) DNA serves as transcriptionally active templates in HIV-infected cells
Overexpression of Twik-related Acid Sensitive K+ (TASK)-1 suppresses HIV-1 replication We sought to extend this finding from a previous study that demonstrated that Twik-related Acid Sensitive K+ channel-1 (TASK-1) suppressed HIV replication [34]. 293T cells were cotransfected with HIV-1 pNL4-3 and TASK-1
Our results show that virus release was reduced by 82.5% in HIV-1-infected cells overexpressing TASK-1 protein compared to cells transfected with the empty vector control (Figure 1a, 1b)
Summary
Unintegrated HIV-1 DNA serves as transcriptionally active templates in HIV-infected cells. HIV-1’s genome is reverse transcribed before the proviral DNA integrates into host cell chromatin. HIV-1 proviral DNA preferentially integrates into open transcriptionally active sites in the host cell chromatin where robust viral gene transcription can occur. Despite the critical role of integration in the lifecycle of all retroviruses, during the course of HIV-1 infection the majority of viral DNA remains unintegrated [1]. Unintegrated HIV-1 DNA (uDNA) is generated during virus replication and serves as DNA templates for transcription. UDNA can circularize by homologous recombination [4] or ligation of interrupted reverse transcription intermediates [5] to form 1-LTR circles. The host restriction factor APOBEC3G has been shown to cause a 2-fold decrease in 2-LTR circle formation in cells infected with Δvif HIV-1 [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
