Unclosed HIV-1 Capsids Suggest a Curled Sheet Model of Assembly

Yu, Zhiheng; Dobro, Megan J.; Woodward, Cora L.; Levandovsky, Artem; Danielson, Cindy M.; Sandrin, Virginie; Shi, Jiong; Aiken, Christopher; Zandi, Roya; Hope, Thomas J.; Jensen, Grant J.

doi:10.1016/j.jmb.2012.10.006

Cited by 60 publications

(109 citation statements)

References 39 publications

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“…No curvature in the middle region might mean no stress, and hence the middle region may be the first to be formed. This is consistent with the curled sheet model [38] and the assembly mechanisms investigated in [22,40], which conclude that pentamers are formed later in assembly, due to high stress.…”

Section: Figuresupporting

confidence: 89%

“…This discusion leads to our conjecture: the narrow [38] show that the HIV-1 capsid narrow end might not close, if conditions are unfavorable. Source: [38] (with permission from Elsevier for reuse of the figure).…”

Section: Figurementioning

confidence: 81%

“…When capsid becomes thermodynamically unfavorable, regions with high stress or high curvature would be the first to break apart. Recent experimental and modeling studies also show that HIV-1 narrow end might not close, if conditions are unfavorable [38], as shown in Figure 5. This discusion leads to our conjecture: the narrow [38] show that the HIV-1 capsid narrow end might not close, if conditions are unfavorable.…”

Section: Figurementioning

confidence: 94%

“…Recent experimental and modeling studies also show that HIV-1 narrow end might not close, if conditions are unfavorable [38], as shown in Figure 5. This discusion leads to our conjecture: the narrow [38] show that the HIV-1 capsid narrow end might not close, if conditions are unfavorable. Source: [38] (with permission from Elsevier for reuse of the figure).…”

Section: Figurementioning

confidence: 94%

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Curvature Concentrations on the HIV-1 Capsid

Liu

Sadre-Marandi

Tavener

et al. 2015

Computational and Mathematical Biophysics

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It is known that the retrovirus capsids possess a fullerene-like structure. These caged polyhedral arrangements are built entirely from hexagons and exactly 12 pentagons according to the Euler theorem. Viral capsids are composed of capsid proteins, which create the hexagon and pentagon shapes by groups of six (hexamer) and five (pentamer) proteins. Different distributions of these 12 pentamers result in icosahedral, tubular, or conical shaped capsids. These pentamer clusters introduce declination and hence curvature on the capsids. This paper provides explicit and quantitative characterization of curvature on virus capsids. The concept of curvature concentration is also introduced. For the HIV (5,7)-cone, it is shown that the curvature concentration at the narrow end is about at least four times higher than that at the broad end. Our modeling results about curvature concentrations on HIV-1 capsids echo the results in the literature that the pentamers are in the regions with the highest stress, although the connection between the two approaches (curvature concentration and stress) is to be explored. This also leads to a conjecture that "HIV-1 capsid narrow end may close last during maturation but open first during entry into a host cell".

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Section: Figuresupporting

confidence: 89%

Section: Figurementioning

confidence: 81%

Section: Figurementioning

confidence: 94%

Section: Figurementioning

confidence: 94%

See 2 more Smart Citations

Curvature Concentrations on the HIV-1 Capsid

Liu

Sadre-Marandi

Tavener

et al. 2015

Computational and Mathematical Biophysics

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“…A different situation exists in the CsA washout assay where viral capsids are allowed to uncoat to different extents in the cytoplasm before being exposed to TRIM-CypA binding by the withdrawal of CsA. A microscopy assay that examined the integrity of viral capsids localizing with rhesus TRIM5␣ cytoplasmic bodies suggested that TRIM proteins associate with intact capsids (46). On the basis of these data, we hypothesize that in the CsA washout assay TRIM-CypA is binding intact capsids or viral complexes that have just started to uncoat.…”

Section: Discussionmentioning

confidence: 99%

Identification of Capsid Mutations That Alter the Rate of HIV-1 Uncoating in Infected Cells

Hulme

Kelley

Okocha

et al. 2015

J Virol

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After viral fusion with the cell membrane, the conical capsid of HIV-1 disassembles by a process called uncoating. We recently utilized the cyclosporine (CsA) washout assay, in which TRIM-CypA-mediated restriction of viral replication is used to detect the state of the viral capsid, to study the kinetics of uncoating in HIV-1-infected cells. Here we have extended this analysis to examine the effects of p24 capsid protein (p24 CA ) mutations and cellular environment on the kinetics of uncoating in infected cells. We found that p24 CA mutations can significantly increase (A92E), delay (E45A and N74D), or have no effect (G94D) on the rate of uncoating and that these alterations are not due to changes in reverse transcription. Inhibition of reverse transcription delayed uncoating kinetics to an extent similar to that of the wild-type virus with all the p24 CA mutant viruses tested. In addition, we observed differences in uncoating in two cell lines, which suggests that the cellular environment can differentially impact the disassembly of wild-type and mutant capsids. Collectively, these experiments suggest that viral and cellular factors are important for the process of uncoating. Finally, these data support the model whereby early steps in reverse transcription facilitate HIV-1 uncoating. IMPORTANCEThe HIV-1 capsid is a cone-shaped structure, composed of the HIV-1-encoded protein p24 CA , which contains the viral RNA and other proteins needed for infection. After the virus enters a target cell, this capsid must disassemble by a process called uncoating. Uncoating is required for HIV-1 infection to progress, but the details of how this process occurs is not known. In this study, we used an in vivo assay to examine the uncoating process in HIV-1-infected cells. We determined that p24 CA mutations could increase or decrease the rate of uncoating and that this rate varied in different cell lines. We also found that reverse transcription of the viral RNA altered the process of uncoating before the p24 CA mutations. Collectively, these experiments provide a better understanding of how viral and cellular factors are involved with a poorly understood step in HIV-1 infection.

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Detection and Tracking of Dual-Labeled HIV Particles Using Wide-Field Live Cell Imaging to Follow Viral Core Integrity

Mamede¹,

Hope²

2016

Methods in Molecular Biology

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Summary Live cell imaging is a valuable technique that allows the characterization of the dynamic processes of the HIV-1 life-cycle. Here, we present a method of production and imaging of dual-labeled HIV viral particles that allows the visualization of two events. Varying release of the intravirion fluid phase marker reveals virion fusion and the loss of the integrity of HIV viral cores with the use of live wide-field fluorescent microscopy.

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Unclosed HIV-1 Capsids Suggest a Curled Sheet Model of Assembly

Cited by 60 publications

References 39 publications

Curvature Concentrations on the HIV-1 Capsid

Curvature Concentrations on the HIV-1 Capsid

Identification of Capsid Mutations That Alter the Rate of HIV-1 Uncoating in Infected Cells

Detection and Tracking of Dual-Labeled HIV Particles Using Wide-Field Live Cell Imaging to Follow Viral Core Integrity

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