Induced Degradation of Tat by Nucleocapsid (NC) via the Proteasome Pathway and Its Effect on HIV Transcription

Department of Bioscience and Biotechnology, Hankuk University of Foreign Studies, Yong-In, Gyung-Gi Do 449-791, Korea. .
Viruses (Impact Factor: 3.35). 04/2013; 5(4):1143-52. DOI: 10.3390/v5041143
Source: PubMed


Human Immunodeficiency Virus type 1 (HIV-1) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS). HIV-1 Tat protein upregulates transcriptional transactivation. The nucleocapsid protein NC of HIV-1 is a component of virion and plays a key role in genome packaging. Herein, we have demonstrated the interaction between NC and Tat by means of a yeast two-hybrid assay, GST pull-down analysis, co-immunoprecipitation and subcellular colocalization analysis. We observed that the level of Tat was significantly reduced in the presence of NC. But NC did not affect mRNA expression level of Tat. The level of Tat in the presence of NC was increased by treating cells with a proteasome inhibitor, MG132. The ubiquitination state of Tat was not seen to increase in the presence of NC, suggesting the proteasomal degradation was independent of ubiquitination. Lowered level of Tat in the presence of NC led to a decrease in Tat-mediated transcriptional transactivation.

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Available from: Seong-Wook Lee
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    ABSTRACT: Viral nucleocapsid proteins (NCs) enwrap the RNA genomes of viruses to form NC-RNA complexes, which act as a template and are essential for viral replication and transcription. Beyond packaging viral RNA, NCs also play important roles in virus replication, transcription, assembly, and budding by interacting with viral and host cellular proteins. Additionally, NCs can inhibit interferon signaling response and function in cell stress response, such as inducing apoptosis. Finally, NCs can be the target of vaccines, benefiting from their conserved gene sequences. Here, we summarize important findings regarding the additional functions of NCs as much more than structural RNA-binding proteins, with specific emphasis on (1) their association with the viral life cycle, (2) their association with host cells, and (3) as ideal candidates for vaccine development. For further resources related to this article, please visit the WIREs website.
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