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

Yu, Zhiheng and Dobro, Megan J. and Woodward, Cora L. and Levandovsky, Artem and Danielson, Cindy M. and Sandrin, Virginie and Shi, Jiong and Aiken, Christopher and Zandi, Roya and Hope, Thomas J. and Jensen, Grant J. (2013) Unclosed HIV-1 Capsids Suggest a Curled Sheet Model of Assembly. Journal of Molecular Biology, 425 (1). pp. 112-123. ISSN 0022-2836.

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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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Additional Information:© 2012 Elsevier Ltd. Received 9 October 2012; Accepted 10 October 2012. Available online 16 October 2012. Z.Y. and M.J.D. contributed equally to this work. 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.
Funding AgencyGrant Number
NIHR01 AI076121
NIHR01 AI407770
Gordon and Betty Moore FoundationUNSPECIFIED
James B. Pendleton Charitable Trust UNSPECIFIED
Subject Keywords:HIV-1; capsid; cryotomography; retroviruses
Record Number:CaltechAUTHORS:20130327-152515876
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Official Citation: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, Unclosed HIV-1 Capsids Suggest a Curled Sheet Model of Assembly, Journal of Molecular Biology, Volume 425, Issue 1, 9 January 2013, Pages 112-123, ISSN 0022-2836, 10.1016/j.jmb.2012.10.006. (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:37658
Deposited By: Ruth Sustaita
Deposited On:27 Mar 2013 22:57
Last Modified:27 Mar 2013 22:57

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