title: HIV-1 capsid uncoating initiates after the first strand transfer of reverse transcription.
abstract: Correct disassembly of the HIV-1 capsid shell, called uncoating, is increasingly recognised as central for multiple steps during retroviral replication. However, the timing, localisation and mechanism of uncoating are poorly understood and progress in this area is hampered by difficulties in measuring the process. Previous work suggested that uncoating occurs soon after entry of the viral core into the cell, but recent studies report later uncoating, at or in the nucleus. Furthermore, inhibiting reverse transcription delays uncoating, linking these processes.
  
  
  
  Here, we have used a combined approach of experimental interrogation of viral mutants and mathematical modelling to investigate the timing of uncoating with respect to reverse transcription. By developing a minimal, testable, model and employing multiple uncoating assays to overcome the disadvantages of each single assay, we find that uncoating is not concomitant with the initiation of reverse transcription. Instead, uncoating appears to be triggered once reverse transcription reaches a certain stage, namely shortly after first strand transfer.
  
  
  
  Using multiple approaches, we have identified a point during reverse transcription that induces uncoating of the HIV-1 CA shell. We propose that uncoating initiates after the first strand transfer of reverse transcription.
authors.affiliation: Retroviral Replication Laboratory, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Cosnefroy
authors.affiliation: Division of Mathematics, University of Dundee, Dundee, DD1 4HN, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Murray
authors.affiliation: Retroviral Replication Laboratory, The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, Mill Hill, London, NW7 1AA, UK. Kate.Bishop@crick.ac.uk.
authors.forename: Kate N
authors.initials: KN
authors.lastname: Bishop
mesh_terms: D002213:Capsid / Q000502:physiology*; D036022:Capsid Proteins; D002460:Cell Line; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D048348:Reverse Transcription; D057646:Virus Uncoating
chemical_list: D036022:Capsid Proteins
keywords: Capsid; HIV-1; Mathematical modelling; Reverse transcription; Uncoating