Opening of the TAR hairpin in the HIV-1 genome causes aberrant RNA dimerization and packaging

Retrovirology

Ben Berkhout¹  Alex Harwig¹  Martine M Vrolijk¹  Atze T Das¹ 

[1] Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands

关键词: RNA structure;    Packaging;    Dimerization;    TAR;    HIV-1;   

Others  :  1209283
DOI  :  10.1186/1742-4690-9-59

 received in 2012-03-27, accepted in 2012-07-04,  发布年份 2012

【 摘 要 】

Background

The TAR hairpin is present at both the 5′ and 3′ end of the HIV-1 RNA genome. The 5′ element binds the viral Tat protein and is essential for Tat-mediated activation of transcription. We recently observed that complete TAR deletion is allowed in the context of an HIV-1 variant that does not depend on this Tat-TAR axis for transcription. Mutations that open the 5′ stem-loop structure did however affect the leader RNA conformation and resulted in a severe replication defect. In this study, we set out to analyze which step of the HIV-1 replication cycle is affected by this conformational change of the leader RNA.

Results

We demonstrate that opening the 5′ TAR structure through a deletion in either side of the stem region caused aberrant dimerization and reduced packaging of the unspliced viral RNA genome. In contrast, truncation of the TAR hairpin through deletions in both sides of the stem did not affect RNA dimer formation and packaging.

Conclusions

These results demonstrate that, although the TAR hairpin is not essential for RNA dimerization and packaging, mutations in TAR can significantly affect these processes through misfolding of the relevant RNA signals.

【 授权许可】

   
2012 Das et al.; licensee BioMed Central Ltd.

【 图 表 】

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