Electron cryo-tomography studies of maturing HIV-1 particles reveal the assembly pathway of the viral core

Abstract

To better characterize the assembly of the HIV-1 core, we have used electron cryo-tomography (ECT) to image infected cells and the viral particles cryo-preserved next to them. We observed progressive stages of virus assembly and egress including flower-like flat gag lattice assemblies, hemispherical budding profiles and virus buds linked to the plasma membrane via a thin membrane neck. The population of budded viral particles contains immature, maturation intermediate and mature core morphologies. Structural characteristics of the maturation intermediates suggest that the core assembly pathway involves the formation of a CA sheet that associates with the condensed ribonucleoprotein (RNP) complex. Our analysis also reveals a correlation between RNP localization within the viral particle and the formation of conical cores, suggesting that the RNP helps drive conical core assembly. Our findings support an assembly pathway for the HIV-1 core that begins with a small CA sheet that associates with the RNP to form the core base, followed by polymerization of the CA sheet along one side of the conical core towards the tip and then closure around the body of the cone.

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