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

JOURNAL OF MOLECULAR BIOLOGY

卷:425

Article

Yu, Zhiheng¹  Dobro, Megan J.²  Woodward, Cora L.³  Danielson, Cindy M.⁴  Sandrin, Virginie⁵  Shi, Jiong⁶  Aiken, Christopher⁶  Zandi, Roya⁷  Hope, Thomas J.⁴  Jensen, Grant J.^3,8 

[1] Howard Hughes Med Inst, CryoEM Shared Resources, Ashburn, VA 20147 USA

[2] Hampshire Coll, Sch Nat Sci, Amherst, MA 01002 USA

[3] CALTECH, Div Biol, Pasadena, CA 91125 USA

[4] Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA

[5] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA

[6] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA

[7] Univ Calif Riverside, Dept Phys & Astron, Riverside, CA 92521 USA

[8] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA

关键词: HIV-1;    capsid;    cryotomography;    retroviruses;   

DOI  :  10.1016/j.jmb.2012.10.006

来源: Elsevier

【 摘 要 】

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 similar to 25% of cytoplasmic HIV complexes captured by TRIM5 alpha 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. (C) 2012 Elsevier Ltd. All rights reserved.

【 授权许可】

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