T = 4 Icosahedral HIV-1 Capsid As an Immunogenic Vector for HIV-1 V3 Loop Epitope Display
by
Zhiqing Zhang 1,†, Maozhou He 1,†
, Shimeng Bai 2,†, Feng Zhang 1, Jie Jiang 2, Qingbing Zheng 1, Shuangquan Gao 1, Xiaodong Yan 1,3, Shaowei Li 1,2,*, Ying Gu 1,2,* and Ningshao Xia 1,2
Zhiqing Zhang 1,†, Maozhou He 1,†, Shimeng Bai 2,†, Feng Zhang 1, Jie Jiang 2, Qingbing Zheng 1, Shuangquan Gao 1, Xiaodong Yan 1,3, Shaowei Li 1,2,*, Ying Gu 1,2,* and Ningshao Xia 1,2
1
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
2
National Institute of Diagnostics and Vaccine Development in Infectious Disease, School of Life Sciences, Xiamen University, Xiamen 361102, China
3
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California-San Diego, San Diego, CA 92093-0378, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Viruses 2018, 10(12), 667; https://doi.org/10.3390/v10120667
Received: 17 October 2018 / Revised: 21 November 2018 / Accepted: 23 November 2018 / Published: 26 November 2018
(This article belongs to the Section Animal Viruses)
The HIV-1 mature capsid (CA) assumes an amorphous, fullerene conical configuration due to its high flexibility. How native CA self-assembles is still unclear despite having well-defined structures of its pentamer and hexamer building blocks. Here we explored the self-assembly of an engineered capsid protein built through artificial disulfide bonding (CA N21C/A22C) and determined the structure of one fraction of the globular particles. CA N21C/A22C was found to self-assemble into particles in relatively high ionic solutions. These particles contained disulfide-bonding hexamers as determined via non-reducing SDS-PAGE, and exhibited two major components of 57.3 S and 80.5 S in the sedimentation velocity assay. Particles had a globular morphology, approximately 40 nm in diameter, in negative-staining TEM. Through cryo-EM 3-D reconstruction, we determined a novel T = 4 icosahedral structure of CA, comprising 12 pentamers and 30 hexamers at 25 Å resolution. We engineered the HIV-1 V3 loop to the CA particles, and found the resultant particles resembled the morphology of their parental particles in TEM, had a positive reaction with V3-specific neutralizing antibodies, and conferred neutralization immunogenicity in mice. Our results shed light on HIV CA assembly and provide a particulate CA for epitope display.
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MDPI and ACS Style
Zhang, Z.; He, M.; Bai, S.; Zhang, F.; Jiang, J.; Zheng, Q.; Gao, S.; Yan, X.; Li, S.; Gu, Y.; Xia, N. T = 4 Icosahedral HIV-1 Capsid As an Immunogenic Vector for HIV-1 V3 Loop Epitope Display. Viruses 2018, 10, 667.
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