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bioRxiv · 10.1101/2022.02.01.478508

HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation

Talledge, N.·Yang, H.·Shi, K.·Yu, G.·Arndt, W. G.·Mendonca, L.·Aihara, H.·Mansky, L. M.·Zhang, W.
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Abstract

Retrovirus immature particle morphology consists of a membrane enclosed, pleomorphic, spherical and incomplete lattice of Gag hexamers. Previously, we demonstrated that human immunodeficiency virus type 2 (HIV-2) immature particles possess a distinct and extensive Gag lattice morphology. To better understand the nature of the continuously curved hexagonal Gag lattice, we have used single particle cryo-electron microscopy with a retrovirus to determine the HIV-2 Gag lattice structure for immature virions. The reconstruction map at 5.5 [A] resolution revealed a stable, wineglass-shaped Gag hexamer structure with structural features consistent with other lentiviral immature Gag structures. Cryo-electron tomography provided evidence for nearly complete ordered Gag lattice structures in HIV-2 immature particles. We also solved a 1.98 [A] resolution crystal structure of the carboxyl-terminal domain (CTD) of the HIV-2 capsid (CA) protein that identified a structured helix 12 supported via an interaction of helix 10 in the absence of the SP1 region of Gag. Residues at the helix 10-12 interface proved critical in maintaining HIV-2 particle release and infectivity. Taken together, our findings provide the first 3D organization of HIV-2 immature Gag lattice and important insights into both HIV Gag lattice stabilization and virus maturation.

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Talledge, N., Yang, H., Shi, K., Yu, G., Arndt, W. G., Mendonca, L., Aihara, H., Mansky, L. M., Zhang, W.. 2022-02-01. HIV-2 Immature Particle Morphology Provides Insights into Gag Lattice Stability and Virus Maturation. https://doi.org/10.1101/2022.02.01.478508

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