Analysis of the mechanical properties of HIV-1 capsid and their impact on the uncoating process

The human immunodeficiency virus (HIV-1) core consists of a protein shell called capsid that encapsulates the viral genome. After a viral particle enters a host cell and prior to nuclear import of viral dsDNA, the capsid has to disassemble in a process called uncoating. Several studies have
shown that uncoating is promoted by reverse transcription
(RT) and regulated by cellular factors. Mutations that alter the stability of the capsid affect the uncoating rate and impair HIV-1 infectivity. Our AFM measurements of the mechanical properties of wild type (WT) and hyperstable
mutant cores (HMC) show that mutations that increases stability and delay uncoating also increase the stiffness of the HIV-1 capsid. In addition, we analyzed the morphological
and stiffness changes of WT and hyperstable cores during
reverse transcription using time-lapse AFM. We find that
hyperstable cores remained intact whereas WT cores disassembled. Based on our findings we propose that the mechanical properties of the HIV-1 capsid must be well balanced toenable capsid uncoating followed by infection.