title: Opening of the TAR hairpin in the HIV-1 genome causes aberrant RNA dimerization and packaging.
abstract: 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.
authors: 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. a.t.das@amc.uva.nl
authors: Atze T
authors: AT
authors: Das
authors: Martine M
authors: MM
authors: Vrolijk
authors: Alex
authors: A
authors: Harwig
authors: Ben
authors: B
authors: Berkhout
mesh_terms: D045744:Cell Line, Tumor; D019281:Dimerization; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D055029:Inverted Repeat Sequences; D009154:Mutation; D009690:Nucleic Acid Conformation; D012326:RNA Splicing; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015533:Transcriptional Activation; D014162:Transfection; D014771:Virion / Q000235:genetics / Q000378:metabolism; D019065:Virus Assembly
chemical_list: D012367:RNA, Viral