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- W2003237436 abstract "Until recently it was a common 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 at least some RTion happens inside the capsid, and may be driving the uncoating. In this theoretical study we consider the problem of mature HIV capsid uncoating driven by polymerization of double stranded (ds) viral DNA by the reverse transcriptase (RT). We take into account that millimolar concentrations of NCp7 contained within the capsid drives aggregation of both single stranded (ss) RNA and dsDNA provided the capsid is intact. The NC-aggregated flexible ssRNA genome occupies only about 5% of capsid volume. The NC-aggregated rigid dsDNA genome is expected to form a tightly wound toroid. For a 103-104 base pair (bp) genome length, the size of this toroid is comparable to, or larger than, the capsid cross-section. At that point either the capsid shell, or the toroid must deform, depending on their comparative rigidities. Since the experimental elasticity parameters of the mature HIV capsid are as yet unknown, we consider both scenarios. In the first case, the capsid is expected to break open (uncoat) when its stress reaches a critical value as described by the theory of elasticity. In the second case, the stress generated by the capsid on the growing toroid eventually stalls the RT. In-vivo HIV uncoating by this mechanism thus must correspond to the first case. Importantly, we predict that a significant fraction of viral dsDNA can be polymerized by RT in the presence of NCp7 before uncoating, even for a low stability capsid." @default.
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- W2003237436 date "2012-01-01" @default.
- W2003237436 modified "2023-10-18" @default.
- W2003237436 title "Uncoating of Mature HIV Capsids Driven by Reverse Transcription" @default.
- W2003237436 doi "https://doi.org/10.1016/j.bpj.2011.11.3486" @default.
- W2003237436 hasPublicationYear "2012" @default.
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