Bioorthogonal click labeling of an amber-free HIV-1 provirus for in-virus single molecule imaging

Ao, Yuanyun; Grover, Jonathan R.; Gifford, Levi; Han, Yang; Zhong, Guohua; Katte, Revansiddha; Li, Wenwei; Bhattacharjee, Rajanya; Zhang, Baoshan; Sauve, Stephanie; Qin, Wenyi; Ghimire, Dibya; Haque, Md Anzarul; Arthos, James; Moradi, Mahmoud; Mothes, Walther; Lemke, Edward A.; Kwong, Peter D.; Melikyan, Gregory B.; Lu, Maolin

doi:10.1016/j.chembiol.2023.12.017

Cited by 2 publications

References 89 publications

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Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening

Thakur,

Katte,

et al. 2024

Preprint

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The hydrophobic fusion peptide (FP), a critical component of the HIV-1 entry machinery, is located at the N terminal stretch of the envelope (Env) gp41 subunit1–3. The receptor-binding gp120 subunit of Env forms a heterodimer with gp41 and assembles into a trimer, in which FP is accessible for antibody binding3. Env conformational changes or “opening” that follow receptor binding result in FP relocating to a newly formed interprotomer pocket at the gp41-gp120 interface where it is sterically inaccessible to antibody4. The mechanistic steps connecting the entry-related transition of antibody accessible-to-inaccessible FP configurations remain unresolved. Here, using SOSIP-stabilized Env ectodomains5, we visualized atomic-level details of a functional entry intermediate, where partially open Env was bound to receptor CD4, co-receptor mimetic antibody 17b, and FP-targeting antibody VRC34.01, demonstrating that FP remains antibody accessible despite substantial receptor-induced Env opening. We determined a series of structures delineating stepwise opening of Env from its closed state to a newly resolved intermediate and defining downstream re-organizations of the gp120-gp41 interface that ultimately resulted in FP burial in an antibody-inaccessible configuration. Our studies improve our understanding of HIV-1 entry and provide information on entry-related conformation reorganization of a key site of HIV vulnerability to neutralizing antibody.

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Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening

Thakur,

Katte,

et al. 2024

Preprint

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Studying Retroviral Life Cycles Using Visible Viruses and Live Cell Imaging

Guerrero,

Lesko,

Evans

et al. 2024

Annual Review of Virology

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Viruses exploit key host cell factors to accomplish each individual stage of the viral replication cycle. To understand viral pathogenesis and speed the development of new antiviral strategies, high-resolution visualization of virus-host interactions is needed to define where and when these events occur within cells. Here, we review state-of-the-art live cell imaging techniques for tracking individual stages of viral life cycles, focusing predominantly on retroviruses and especially human immunodeficiency virus type 1, which is most extensively studied. We describe how visible viruses can be engineered for live cell imaging and how nonmodified viruses can, in some instances, be tracked and studied indirectly using cell biosensor systems. We summarize the ways in which live cell imaging has been used to dissect the retroviral life cycle. Finally, we discuss select challenges for the future including the need for better labeling strategies, increased resolution, and multivariate systems that will allow for the study of full viral replication cycles.

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Bioorthogonal click labeling of an amber-free HIV-1 provirus for in-virus single molecule imaging

Cited by 2 publications

References 89 publications

Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening

Conformational trajectory of the HIV-1 fusion peptide during CD4-induced envelope opening

Studying Retroviral Life Cycles Using Visible Viruses and Live Cell Imaging

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