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• W3204174132 abstract "Abstract Viral replication in HIV-1 relies on a fullerene-shaped capsid to transport genetic material deep into the nucleus of an infected cell. Capsid stability is linked to the presence of cofactors, including inositol hexakisphosphate (IP 6 ) that bind to pores found in the capsid. Using extensive all-atom molecular dynamics simulations of HIV-1 cores imaged from cryo-electron tomography (cryo-ET) in intact virions, which contain IP 6 and a ribonucleoprotein complex, we find markedly striated patterns of strain on capsid lattices. The presence of these cofactors also increases rigidity of the capsid. Conformational analysis of capsid (CA) proteins show CA accommodates strain by locally flexing away from structures resolved using x-ray crystallography and cryo-electron microscopy. Then, cryo-ET of HIV-1 cores undergoing endogenous reverse transcription demonstrate that lattice strain increases in the capsid prior to mechanical failure and that the capsid ruptures by crack propagation along regions of high strain. These results uncover HIV-1 capsid properties involved in their critical disassembly process. Significance statement The mature capsids of HIV-1 are transiently stable complexes that self-assemble around the viral genome during maturation, and uncoat to release preintegration complexes that archive a double-stranded DNA copy of the virus in the host cell genome. However, a detailed view of how HIV cores rupture remains lacking. Here, we elucidate the physical properties involved in capsid rupture using a combination of large-scale all-atom molecular dynamics simulations and cryo-electron tomography. We find that intrinsic strain on the capsid forms highly correlated patterns along the capsid surface, along which cracks propagate. Capsid rigidity also increases with high strain. Our findings provide fundamental insight into viral capsid uncoating." @default.
• W3204174132 created "2021-10-11" @default.
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• W3204174132 date "2021-10-01" @default.
• W3204174132 modified "2023-10-16" @default.
• W3204174132 title "Strain and crack propagation of HIV-1 capsids during uncoating" @default.
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• W3204174132 doi "https://doi.org/10.1101/2021.09.30.462583" @default.
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