Roles of Gag-RNA interactions in HIV-1 virus assembly deciphered by single-molecule localization microscopy

Yang, Yantao; Qu, Na; Tan, Jie; Rushdi, Muaz Nik; Krueger, Christopher J.; Chen, Antony K.

doi:10.1073/pnas.1805728115

Cited by 26 publications

(44 citation statements)

References 40 publications

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“…Later on, a comparison of apparent diffusion coefficient distribution highlighted the role of the NC-RNA binding domain of Gag in HIV-1 assembly in adherent cells [71] or in CD4 T-cells [49]. Recently, studies by Floderer et al [38,48] in T cells, and Yang et al [72] in adherent cells, used sptPALM to track Gag molecules and to confirm the important role of the gRNA and the NC domain of Gag in the generation of Gag clusters at the plasma membrane of the host cell for efficient HIV-1 assembly. Floderer et al [38,48] showed that gRNA in the context of a provirus acts as a spatiotemporal coordinator of the membrane assembly process, rather than only serving as an attractor for Gag molecules to the assembly site.…”

Section: Towards a Real Time Molecular Description Of Hiv Assemblymentioning

confidence: 99%

Monitoring HIV-1 Assembly in Living Cells: Insights from Dynamic and Single Molecule Microscopy

Inamdar

Floderer

Favard

et al. 2019

Viruses

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The HIV-1 assembly process is a multi-complex mechanism that takes place at the host cell plasma membrane. It requires a spatio-temporal coordination of events to end up with a full mature and infectious virus. The molecular mechanisms of HIV-1 assembly have been extensively studied during the past decades, in order to dissect the respective roles of the structural and non-structural viral proteins of the viral RNA genome and of some host cell factors. Nevertheless, the time course of HIV-1 assembly was observed in living cells only a decade ago. The very recent revolution of optical microscopy, combining high speed and high spatial resolution, in addition to improved fluorescent tags for proteins, now permits study of HIV-1 assembly at the single molecule level within living cells. In this review, after a short description of these new approaches, we will discuss how HIV-1 assembly at the cell plasma membrane has been revisited using advanced super resolution microscopy techniques and how it can bridge the study of viral assembly from the single molecule to the entire host cell.

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Section: Towards a Real Time Molecular Description Of Hiv Assemblymentioning

confidence: 99%

Monitoring HIV-1 Assembly in Living Cells: Insights from Dynamic and Single Molecule Microscopy

Inamdar

Floderer

Favard

et al. 2019

Viruses

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“…Capsid proteins diffusing in 245 from infinity towards the growth surface must pass through a neck region with negative 246 Gauss curvature. This requirement applies even to assembly processes in which 247 RNA-protein interactions play a role [38] or proteins are targeted near capsid assembly 248 sites [39]. Consistent with this explanation is the fact that the interaction strength between the 268 capsid proteins of immature retroviruses is believed to be quite weak [42], which could 269 place them below the critical point.…”

Section: /19mentioning

confidence: 98%

“…This hole survives the pinch-off process and 36 only about 2/3 of the membrane of the completed immature HIV-1 virus is covered by 37 proteins. It is important to note that hole formation is not observed for other enveloped 38 viruses such as the Herpes and alphaviruses. Figure 1 suggests that the transport 39 current supplying proteins to the curved neck region somehow has "dried-up" before the 40 spontaneous part of the assembly could complete.…”

mentioning

confidence: 99%

Gaussian curvature and the budding kinetics of enveloped viruses

Hagan

Bruinsma

Dharmavaram

et al. 2018

Preprint

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The formation of a membrane-enveloped virus such as HIV-1 starts with the assembly of a curved layer of capsid proteins lining the interior of the plasma membrane (PM) of the host cell. This layer grows into a spherical shell enveloped by a lipid membrane that is connected to the PM via a curved neck ("budding"). For many enveloped viruses the scission of this neck is not spontaneous. Instead, the elaborate "ESCRT" cell machinery needs to be recruited to carry out that task. It is not clear why this is necessary since scission is spontaneous for much simpler systems, such as vesiculation driven by phase-separation inside lipid bilayers. Recently, Brownian dynamics simulations of enveloped virus budding reproduced protracted pausing and stalling after formation of the neck [1], which suggest that the origin of pausing/stalling is to be found in the physics of the budding process. Here, we show that the pausing/stalling observed in the simulations can be understood as a purely kinetic phenomenon associated with a "geometrical" energy barrier that must be overcome by capsid proteins diffusing along the membrane prior to incorporation into the viral capsid. This geometrical energy barrier is generated by the conflict between the positive Gauss curvature of the capsid and the large negative Gauss curvature of the neck region. The theory is compared with the Brownian simulations of the budding of enveloped viruses.

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“…d-A less arbitrary method is to fit all the MSD(t) curve with the MSD(t)=Dt  approximation and take benefit of numerous noisy curves to establish statistically relevant distribution of motion, allowing to qualitatively classify the type of motion observed in the cell. This technique has been used to observe directed motion close to the assembly site in [58]. e-A more rigorous analysis aims at disentangling the part of Brownian and directed motion in the trajectory using the Langevin equation of motion.…”

Section: Towards a Real Time Molecular Description Of Hiv Assembly Inmentioning

confidence: 99%

Monitoring HIV-1 Assembly in Living Cells: Insight from Dynamic and Single Molecule Microscopy

Inamdar¹,

Floderer²,

Favard³

et al. 2018

Preprint

View full text Add to dashboard Cite

HIV-1 assembly is a complex mechanism taking place at the plasma membrane of the host cell. It requires nice spatial and temporal coordination to end up with a full immature virus. Researchers have extensively studied HIV-1 assembly molecular mechanism during the past decades, in order to dissect the respective roles of viral proteins, viral genome and host cell factors. Nevertheless, the time course of the process has been observed in living cells only a decade ago. The very recent revolution of optical microscopy, combining high speed and high spatial resolution now permit to study assemblies and their consequences at the single molecule level within (living) cells. In this review, after a short description of these new approaches, we will show how HIV-1 assembly in cells has been revisited using these advanced super resolution microscopy techniques and how much it could make a bridge in studying assembly from the single molecule to the host cell.

show abstract

Roles of Gag-RNA interactions in HIV-1 virus assembly deciphered by single-molecule localization microscopy

Cited by 26 publications

References 40 publications

Monitoring HIV-1 Assembly in Living Cells: Insights from Dynamic and Single Molecule Microscopy

Monitoring HIV-1 Assembly in Living Cells: Insights from Dynamic and Single Molecule Microscopy

Gaussian curvature and the budding kinetics of enveloped viruses

Monitoring HIV-1 Assembly in Living Cells: Insight from Dynamic and Single Molecule Microscopy

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