HIV-1 capsid uncoating initiates after the first strand transfer of reverse transcription. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Cosnefroy, Ophélie; Murray, Philip; Bishop, Kate
• Is Part Of: Retrovirology. Volume 13:Issue 1(2016)
• Page Start: 1
• Page End: 17
• Publication Date: 2016-12
• Subjects: HIV-1 -- Capsid -- Uncoating -- Reverse transcription -- Mathematical modelling; Retroviruses -- Periodicals; 579.2569
• DOI: 10.1186/s12977-016-0292-7
• Languages: English
• ISSNs: 1742-4690

Abstract

Abstract Background 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. Results 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. Conclusions 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.