Elasticity of the HIV-1 core facilitates nuclear entry and infection

• DOI: 10.1371/journal.ppat.1012537
• Publication Date: 2024-09-11T17:37:19Z
• Authors: Akshay Deshpande; Alexander J. Bryer; Jonathan R. Andin...; Jiong Shi; Jun Hong; Cameron Torres; Shimon Harel; Ashwanth C. Francis; Juan R. Perilla; Christopher Aiken; Itay Rousso
• Keywords: Infectivity; Elasticity; Nuclear pore

HIV-1 infection requires passage of the viral core through nuclear pore cell, a process that depends on functions capsid. Recent studies have shown cores enter nucleus prior to capsid disassembly. Interactions with complex are necessary but not sufficient for entry, and mechanism by which traverses comparably sized is unknown. Here we show highly elastic this property linked entry infectivity. Using atomic force microscopy-based approaches, found purified wild type rapidly returned their normal conical morphology following severe compression. Results from independently performed molecular dynamic simulations mature also revealed its property. Analysis four mutants exhibit impaired mutant brittle. Adaptation two viruses in cell culture resulted additional substitutions restored elasticity rescued infectivity entry. We capsid-targeting compound PF74 antiviral drug Lenacepavir reduce block at concentrations preserve interactions between envelope. Our results indicate fundamental enables thereby facilitating infection. These provide new insights into role mechanisms inhibitors.