Albany 2015:Book of Abstracts
June 9-13 2015
©Adenine Press (2012)
Reverse Transcription Driven Uncoating of Mature HIV Capsids
Until recently it was a commonly accepted notion that reverse transcription (RTion) in retroviruses, including HIV, takes place within the cytoplasm of the infected cell after uncoating of the mature capsid. However, accumulating evidence suggests that the RTion process happens largely within the mature capsid core, which protects the viral genome from host factors and maintains high local concentrations of the essential viral proteins within the RTion complex. In this work, we consider the problem of mature HIV capsid uncoating driven by polymerization of double stranded (ds) pro-viral DNA during RTion. The millimolar concentrations of nucleocapsid protein (NC) contained within the capsid drives aggregation of both single-stranded (ss) gRNA and dsDNA, provided the capsid is intact. Flexible gRNA is aggregated by NC into a ribonucleoprotein complex occupying only a small fraction of the capsid volume. While the self-volume of the full-length pro-viral DNA (∼104 bp) is the same as of its diploid gRNA genome, the dsDNA is very rigid, and gets condensed by NC into a large toroidal globule. We estimate that the weak dsDNA self-attraction induced by NC can lead to the size of the dsDNA globule similar to the size of the capsid. We predict very low value of mature capsid stability parameter for which it can be uncoated by pro-viral DNA condensed by NC. We describe the phase diagram that relates the volume of double stranded pro-viral DNA synthesized within the capsid, the strength of its NC-induced self-attraction, and the stability of the capsid at the point of uncoating. We discuss the current in vivo evidence for the relationship between the RTion and mature capsid uncoating in HIV.
1 Department of Biochemistry