Real-time imaging of individual virion-triggered cortical actin dynamics for human immunodeficiency virus entry into resting CD4 T cells

Yin, Wen; Li, Wei; Li, Qin; Liu, Yuanyuan; Ji, Liu; Ren, Min; Ma, Yingxin; Zhang, Zhiping; Zhang, Xiaowei; Wu, Yuntao; Jiang, Shibo; Zhang, Xian-En; Cui, Zongqiang

doi:10.1039/c9nr07359k

Cited by 27 publications

(31 citation statements)

References 46 publications

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“…By imaging quantum dots (QDs) containing viral particles with DiD-labeled viral membranes, the group of Zongqiang Cui observed that in CD4+ T lymphocytes and CEM-ss, the DiD and QD fluorescence signals separated at the cell surface. The DiD signal disappeared, while the QDs moved rapidly into the host cell cytosol, suggesting viral entry after fusion with the plasma membrane [54].…”

Section: Fusion With the Plasma Membranementioning

confidence: 99%

“…Tracking of QDs-containing HIV-1 in primary macrophages expressing eGFP-Lifeact (F-actin labeling) showed accumulation of F-actin at the site of the viral fusion, followed by generation of a pore-like channel made of cortical actin, allowing the virion to enter the host cell cytoplasm. During channel formation, this site was enriched in α-actinin [54]. In Heladerived cells, HIV-1 viruses moved along actin filaments at the cell periphery and their movements were blocked by actin polymerization inhibitors, suggesting a role of actin in HIV-1 transport [44].…”

Section: Journey Toward the Nucleusmentioning

confidence: 99%

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Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage

Mukherjee

Boutant²,

Réal³

et al. 2021

Viruses

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During the last two decades, progresses in bioimaging and the development of various strategies to fluorescently label the viral components opened a wide range of possibilities to visualize the early phase of Human Immunodeficiency Virus 1 (HIV-1) life cycle directly in infected cells. After fusion of the viral envelope with the cell membrane, the viral core is released into the cytoplasm and the viral RNA (vRNA) is retro-transcribed into DNA by the reverse transcriptase. During this process, the RNA-based viral complex transforms into a pre-integration complex (PIC), composed of the viral genomic DNA (vDNA) coated with viral and host cellular proteins. The protective capsid shell disassembles during a process called uncoating. The viral genome is transported into the cell nucleus and integrates into the host cell chromatin. Unlike biochemical approaches that provide global data about the whole population of viral particles, imaging techniques enable following individual viruses on a single particle level. In this context, quantitative microscopy has brought original data shedding light on the dynamics of the viral entry into the host cell, the cytoplasmic transport, the nuclear import, and the selection of the integration site. In parallel, multi-color imaging studies have elucidated the mechanism of action of host cell factors implicated in HIV-1 viral cycle progression. In this review, we describe the labeling strategies used for HIV-1 fluorescence imaging and report on the main advancements that imaging studies have brought in the understanding of the infection mechanisms from the viral entry into the host cell until the provirus integration step.

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Section: Fusion With the Plasma Membranementioning

confidence: 99%

Section: Journey Toward the Nucleusmentioning

confidence: 99%

Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage

Mukherjee

Boutant²,

Réal³

et al. 2021

Viruses

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“…QDs encapsulated fluorescent virus particles and SVT helped to unravel that the individual HIV viruses could regulate subtle rearrangement in the cortical actin barrier, which opens a door and promotes virus entry (Yin et al, 2020). Actin binding protein, α‐actinin, performs an essential role in the dynamics of actin when HIV enters living cells.…”

Section: Applications Of Nanotechnology In Virus Tracking and Virus Infection Mechanism Researchmentioning

confidence: 99%

Applications of nanotechnology in virus detection, tracking, and infection mechanisms

Kang

Tahir

Wang

et al. 2021

WIREs Nanomed Nanobiotechnol

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Viruses are among the most infectious pathogens, responsible for the highest death toll around the world. Lack of effective clinical drug for most of the viruses emphasizes the rapid and accurate diagnosis at early stages of infection to prevent rapid spread of the pathogens. Nanotechnology is an emerging field with applications in various domains, where nano‐biomedical science has many significant contributions such as effective delivery of drugs/therapeutic molecules to specific organs, imaging, sensitive detection of virus, and their accurate tracking in host cells. The nanomaterials reported for virus detection and tracking mainly include magnetic and gold NPs, ZnO/Pt‐Pd, graphene, and quantum dots (QDs). In addition, the single virus tracking technology (SVT) allowed to track the life cycle stages of an individual virus for better understanding of their dynamics within the living cells. Inorganic as well as non‐metallic fluorescent materials share the advantages of high photochemical stability, a wide range of light absorption curves and polychromatic emission. Hence, are considered as potential fluorescent nano‐probes for SVT. However, there are still some challenges: (i) clinical false positive rate of some detection methods is still high; (ii) in the virus tracking process, less adaptability of QDs owing to larger size, flicker, and possible interference with virus function; and (iii) in vivo tracking of a single virus, in real time needs further refinement. In the future, smaller, non‐toxic, and chemically stable nanomaterials are needed to improve the efficiency and accuracy of detection, and monitoring of virus infections to curb the mortalities. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures

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“…It also intensely localizes to and participates in the assembly of actomyosin contractile rings to drive membrane movements associated with yeast cytokinesis 3 . Recent evidence has shown that α-actinin aggregates at the entry site of Human Immunodeficiency Virus (HIV) to CD4 + T cells in order to regulate actin cortex rearrangements during membrane fusion, making αactinin a potential target for antiviral therapy 4 . Fascin, another key actin crosslinker, on the other hand, is predominantly present at the cell leading edge.…”

Section: Introductionmentioning

confidence: 99%

Actin crosslinker competition and sorting drive emergent GUV size-dependent actin network architecture

Bashirzadeh

Redford

Lorpaiboon

et al. 2020

Preprint

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Robust spatiotemporal organization of cytoskeletal networks is crucial, enabling cellular processes such as cell migration and division. α-Actinin and fascin are two actin crosslinking proteins localized to distinct regions of eukaryotes to form actin bundles with optimized spacing for cell contractile machinery and sensory projections, respectively. In vitro reconstitution assays and coarse-grained simulations have shown that these actin bundling proteins segregate into distinct domains with a bundler size-dependent competition-based mechanism, driven by the minimization of F-actin bending energy. However, it is not known how physical confinement imposed by the cell membrane contributes to sorting of actin bundling proteins and the concomitant reorganization of actin networks in intracellular environment. Here, by encapsulating actin, α-actinin, and fascin in giant unilamellar vesicles (GUVs), we show that the size of such a spherical boundary determines equilibrated structure of actin networks among three typical structures: single rings, astral structures, and star-like structures. We show that α-actinin bundling activity and its tendency for clustering actin is central to the formation of these structures. By analyzing physical features of crosslinked actin networks, we show that spontaneous sorting and domain formation of α-actinin and fascin are intimately linked to the resulting structures. We propose that the observed boundary-imposed effect on sorting and structure formation is a general mechanism by which cells can select between different structural dynamical steady states.

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Real-time imaging of individual virion-triggered cortical actin dynamics for human immunodeficiency virus entry into resting CD4 T cells

Abstract: Using QD-encapsulated HIV particles and single-virus tracking, we revealed virus-regulated cortical actin dynamics during HIV entry into CD4 T cells.

Cited by 27 publications

References 46 publications

Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage

Imaging Viral Infection by Fluorescence Microscopy: Focus on HIV-1 Early Stage

Applications of nanotechnology in virus detection, tracking, and infection mechanisms

Actin crosslinker competition and sorting drive emergent GUV size-dependent actin network architecture

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