Abstract
BackgroundThe human immunodeficiency virus (HIV-1) capsid is a self-assembled protein shell that contains the viral genome. During the stages between viral entry into a host cell and nuclear import of the viral DNA, the capsid dissociates in a process known as uncoating, which leads to the release of the viral genetic material. Mutations that alter the stability of the capsid affect the uncoating rate and impair HIV-1 infectivity.ResultsTo gain further insight into the role of capsid stability during uncoating, we used atomic force spectroscopy to quantify the stiffness of the capsid. Empty in vitro assemblies of wild type (WT) and mutant recombinant HIV-1 capsid protein (CA) as well as isolated WT and mutant HIV-1 cores (i.e., filled capsids) were analyzed. We find that hyperstable CA mutant assemblies (A204C, A14C/E45C, E45A and E45A/R132T) are significantly stiffer than WT assemblies. However, the hardening effect of disulfide crosslinking (A204C and A14C/E45C) is lower than that of hydrophobic interactions (E45A and E45A/R132T).ConclusionsOur results demonstrate that mutations that increase the intrinsic stability of the HIV-1 capsid have an increased stiffness of their lattice.
Highlights
The human immunodeficiency virus (HIV-1) capsid is a self-assembled protein shell that contains the viral genome
capsid protein (CA) assemblies form tubes and capsid‐like cones Purified recombinant CA protein was assembled into capsids under high-salt conditions and their structures were visualized by topographic atomic force microscope (AFM) (Figs. 1, 2)
The same two forms were found for hyperstable mutant CA assemblies: E45A (Fig. 1d) and E45A/R132T, A204C and A14C/E45C, with varying relative abundances of tubes and cones
Summary
The human immunodeficiency virus (HIV-1) capsid is a self-assembled protein shell that contains the viral genome. The human immunodeficiency virus (HIV) is an enveloped retrovirus whose genetic material is initially in single-stranded RNA form. The viral genomic RNA is encapsidated within a cone-shaped capsid. The HIV capsid is a thin conical shell 100–120 nm in length that is formed during viral maturation by the assembly of about 1500 capsid protein (CA) molecules, which are organized into about 250 hexamers and 12 pentamers. The viral RNA is reverse transcribed into double-stranded DNA and is integrated into a host chromosome.
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