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

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

doi:10.1016/j.jmb.2012.10.006

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

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

^*Corresponding author for this work

Cell & Developmental Biology

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

The RNA genome of retroviruses is encased within a protein capsid. To gather insight into the assembly and function of this capsid, we used electron cryotomography to image human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) particles. While the majority of viral cores appeared closed, a variety of unclosed structures including rolled sheets, extra flaps, and cores with holes in the tip were also seen. Simulations of nonequilibrium growth of elastic sheets recapitulated each of these aberrations and further predicted the occasional presence of seams, for which tentative evidence was also found within the cryotomograms. To test the integrity of viral capsids in vivo, we observed that ∼ 25% of cytoplasmic HIV complexes captured by TRIM5α had holes large enough to allow internal green fluorescent protein (GFP) molecules to escape. Together, these findings suggest that HIV assembly at least sometimes involves the union in space of two edges of a curling sheet and results in a substantial number of unclosed forms.

Original language	English (US)
Pages (from-to)	112-123
Number of pages	12
Journal	Journal of Molecular Biology
Volume	425
Issue number	1
DOIs	https://doi.org/10.1016/j.jmb.2012.10.006
State	Published - Jan 9 2013

Funding

This work was supported in part by NIH Grants 2P50GM082545-06 (to T.J.H. and G.J.J.), R01 AI076121 (to C.A.), and R01 AI407770 (to T.J.H.); National Science Foundation Grant DMR-06-45668 (to R.Z.); and gifts to Caltech from the Gordon and Betty Moore Foundation and to Northwestern from the James B. Pendleton Charitable Trust. The following was obtained from the NIH AIDS Research and Reference Reagent Program: 183-H12-5C hybridoma from Dr. Bruce Chesebro. We thank Dr. Ben Chen for providing the HIV Gag-iGFP plasmid, Dr. Joseph Sodroski for cells expressing rhTRIM5α, Dylan Morris for help with the supplementary movies, Drs. Jordan Schooler and Elizabeth Wright for help with data collection, and Drs. Wesley Sundquist and Edward Campbell for critically reading the manuscript.

Keywords

HIV-1
capsid
cryotomography
retroviruses

ASJC Scopus subject areas

Biophysics
Structural Biology
Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jmb.2012.10.006

Cite this

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title = "Unclosed HIV-1 Capsids Suggest a Curled Sheet Model of Assembly",

abstract = "The RNA genome of retroviruses is encased within a protein capsid. To gather insight into the assembly and function of this capsid, we used electron cryotomography to image human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) particles. While the majority of viral cores appeared closed, a variety of unclosed structures including rolled sheets, extra flaps, and cores with holes in the tip were also seen. Simulations of nonequilibrium growth of elastic sheets recapitulated each of these aberrations and further predicted the occasional presence of seams, for which tentative evidence was also found within the cryotomograms. To test the integrity of viral capsids in vivo, we observed that ∼ 25% of cytoplasmic HIV complexes captured by TRIM5α had holes large enough to allow internal green fluorescent protein (GFP) molecules to escape. Together, these findings suggest that HIV assembly at least sometimes involves the union in space of two edges of a curling sheet and results in a substantial number of unclosed forms.",

keywords = "HIV-1, capsid, cryotomography, retroviruses",

author = "Zhiheng Yu and Dobro, {Megan J.} and Woodward, {Cora L.} and Artem Levandovsky and Danielson, {Cindy M.} and Virginie Sandrin and Jiong Shi and Christopher Aiken and Roya Zandi and Hope, {Thomas J} and Jensen, {Grant J.}",

note = "Funding Information: This work was supported in part by NIH Grants 2P50GM082545-06 (to T.J.H. and G.J.J.), R01 AI076121 (to C.A.), and R01 AI407770 (to T.J.H.); National Science Foundation Grant DMR-06-45668 (to R.Z.); and gifts to Caltech from the Gordon and Betty Moore Foundation and to Northwestern from the James B. Pendleton Charitable Trust. The following was obtained from the NIH AIDS Research and Reference Reagent Program: 183-H12-5C hybridoma from Dr. Bruce Chesebro. We thank Dr. Ben Chen for providing the HIV Gag-iGFP plasmid, Dr. Joseph Sodroski for cells expressing rhTRIM5α, Dylan Morris for help with the supplementary movies, Drs. Jordan Schooler and Elizabeth Wright for help with data collection, and Drs. Wesley Sundquist and Edward Campbell for critically reading the manuscript. ",

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AU - Dobro, Megan J.

AU - Woodward, Cora L.

AU - Levandovsky, Artem

AU - Danielson, Cindy M.

AU - Sandrin, Virginie

AU - Shi, Jiong

AU - Aiken, Christopher

AU - Zandi, Roya

AU - Hope, Thomas J

AU - Jensen, Grant J.

N1 - Funding Information: This work was supported in part by NIH Grants 2P50GM082545-06 (to T.J.H. and G.J.J.), R01 AI076121 (to C.A.), and R01 AI407770 (to T.J.H.); National Science Foundation Grant DMR-06-45668 (to R.Z.); and gifts to Caltech from the Gordon and Betty Moore Foundation and to Northwestern from the James B. Pendleton Charitable Trust. The following was obtained from the NIH AIDS Research and Reference Reagent Program: 183-H12-5C hybridoma from Dr. Bruce Chesebro. We thank Dr. Ben Chen for providing the HIV Gag-iGFP plasmid, Dr. Joseph Sodroski for cells expressing rhTRIM5α, Dylan Morris for help with the supplementary movies, Drs. Jordan Schooler and Elizabeth Wright for help with data collection, and Drs. Wesley Sundquist and Edward Campbell for critically reading the manuscript.

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N2 - The RNA genome of retroviruses is encased within a protein capsid. To gather insight into the assembly and function of this capsid, we used electron cryotomography to image human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) particles. While the majority of viral cores appeared closed, a variety of unclosed structures including rolled sheets, extra flaps, and cores with holes in the tip were also seen. Simulations of nonequilibrium growth of elastic sheets recapitulated each of these aberrations and further predicted the occasional presence of seams, for which tentative evidence was also found within the cryotomograms. To test the integrity of viral capsids in vivo, we observed that ∼ 25% of cytoplasmic HIV complexes captured by TRIM5α had holes large enough to allow internal green fluorescent protein (GFP) molecules to escape. Together, these findings suggest that HIV assembly at least sometimes involves the union in space of two edges of a curling sheet and results in a substantial number of unclosed forms.

AB - The RNA genome of retroviruses is encased within a protein capsid. To gather insight into the assembly and function of this capsid, we used electron cryotomography to image human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) particles. While the majority of viral cores appeared closed, a variety of unclosed structures including rolled sheets, extra flaps, and cores with holes in the tip were also seen. Simulations of nonequilibrium growth of elastic sheets recapitulated each of these aberrations and further predicted the occasional presence of seams, for which tentative evidence was also found within the cryotomograms. To test the integrity of viral capsids in vivo, we observed that ∼ 25% of cytoplasmic HIV complexes captured by TRIM5α had holes large enough to allow internal green fluorescent protein (GFP) molecules to escape. Together, these findings suggest that HIV assembly at least sometimes involves the union in space of two edges of a curling sheet and results in a substantial number of unclosed forms.

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KW - cryotomography

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JF - Journal of Molecular Biology

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ER -

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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