Virus-Based Nanoparticles of Simian Virus 40 in the Field of Nanobiotechnology
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REVIEW Nanobiotechnology www.biotechnology-journal.com Virus-Based Nanoparticles of Simian Virus 40 in the Field of Nanobiotechnology Wenjing Zhang, Xian-En Zhang,* and Feng Li* novel functional nanostructures for tar- Biomolecular nanostructures derived from living organisms, such as geted delivery, imaging and sensing, protein cages, fibers, and layers are drawing increasing interests as natural catalysis, immunotherapy, tissue engi- [1–3] biomaterials. The virus-based nanoparticles (VNPs) of simian virus 40 neering, and theranostics. Alarge variety of different viruses, ranging from (SV40), with a cage-like structure assembled from the major capsid protein bacteriophages and plant viruses to animal of SV40, have been developed as a platform for nanobiotechnology in the viruses and human viruses with different recent decade. Foreign nanomaterials (e.g., quantum dots (QDs) and gold shapes, sizes, and compositions, are being nanoparticles (AuNPs)) can be positioned in the inner cavity or on the utilized for nanobiotechnological innova- [4–8] outer surface of SV40 VNPs, through self-assembly by engineering the tions. Here we concentrate on the nanoparticle (NP)-protein interfacial interactions. Construction of these explorations of an animal virus, simian virus 40 (SV40) for materials purposes in hybrid nanostructures has enabled integration of different functionalities. this emerging field. This review briefly summarizes the applications of SV40 VNPs in this SV40 belongs to the polyomavirus multidisciplinary field, including NP encapsulation, templated assembly of family, which has been extensively stud- nanoarchitectures, nanophotonics, and fluorescence imaging. ied as a model virus, so the background is relatively clear. SV40 has a closed circular dsDNA genome of 5.2 kb which com- prises three parts including a non- 1. Introduction translated regulatory region, the early region that encodes the replication proteins, and thelateregionthatencodesthe Viruses are natural materials providing unique nanoscale capsid proteins (the major capsid protein VP1, and the minor scaffolds that bridge molecular biology and nanotechnology. capsid proteins VP2 and VP3) and a maturation protein Viruses possess several advantages for nanomaterials purposes, (agnoprotein).[9] SV40 infects almost all mammalian species – including precise spatial arrangement of their capsid proteins and nucleated cell types.[10 12] Therefore, SV40 was once – into well-defined structures, monodispersity, convenient prep- exploited extensively as a gene delivery vehicle.[12 14] In the aration, and addressable modification. When virus-based past decade, virus-based nanoparticles (VNPs) of SV40, materials are exploited as templates or scaffolds to construct assembled from pentamers of the major capsid protein nanoarchitectures, foreign materials can be positioned in VP1, began to attract attention as a nanomaterial for the inner cavity or/and on the outer surface of their capsid, applications in nanobiotechnology.[15,16] through either direct synthesis or controllable self-assembly. Combined with chemically synthesized nanomaterials of various properties, virus-based materials have been expanding 2. VNPs Derived From SV40 their applications in the field of nanobiotechnology, generating SV40 has a nonenveloped icosahedral capsid with a diameter of about 45 nm. The shell of SV40 virion is composed of 72 VP1 W. Zhang, Prof. F. Li State Key Laboratory of Virology pentamers including twelve 5-coordinated pentamers centered Wuhan Institute of Virology on the strict fivefold axes and sixty 6-coordinated pentamers Chinese Academy of Sciences situated at T ¼ 7 icosahedral surface lattice with only local Wuhan 430071, China fivefold symmetry. The C-terminal arms of VP1 subunits interact E-mail: [email protected] with neighboring pentamers and provide the stability basis of the W. Zhang capsid (Figure 1A and B). The CD-loops, the disulfide bonds, the University of Chinese Academy of Sciences Beijing 101407, China interfaces between strict and local pentamers, and the cation- binding sites also play important roles in the capsid stability. A Prof. X.-E. Zhang National Laboratory of Biomacromolecules single copy of VP2 or VP3 is associated with the inner surface of CAS Center for Excellence in Biomacromolecules the conical opening of each VP1 pentamer, bridging the outer Institute of Biophysics, Chinese Academy of Sciences shell and the internal viral minichromosome.[17,18] SV40 VP1 Beijing 100101, China pentamers are capable of self-assembling into polymorphic E-mail: [email protected] empty capsid-like structures in vitro as influenced by calcium DOI: 10.1002/biot.201700619 ions, pH, and ionic strength. Besides the approximately 40 nm Biotechnol. J. 2018, 13, 1700619 1700619 (1 of 7) © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.advancedsciencenews.com www.biotechnology-journal.com T¼7 72-pentamer icosahedral particles, VP1 pentamers can also Wenjing Zhang received her BS from T¼3 T¼4 form 25 to 35 nm -or -like icosahedral intermediate Zhenzhou University in 2009. She is particles and approximately 20 nm T¼1 icosahedral tiny [19,20] currently a PhD candidate at Wuhan particles, as well as tube-like assemblies (Figure 1C). The Institute of Virology, Chinese ability of SV40 VP1 pentamers to form polymorphic particles, Academy of Sciences under fl makes them exible in nanobiotechnological applications by Professor Feng Li. Her research providing more possibilities in nanostructure fabrication. interests are focused on protein fi SV40 VNPs can be readily modi ed by genetic engineering or nanostructures and their fi chemical modi cation to introduce required functions, as applications in nanobiotechnology several surface-exposed loops of VP1 provide potential sites to and immunology. display peptides of interest and the N-terminal fragment of VP1 protruding to the inner cavity provides a potential site to install – Xian-En Zhang is a distinguished functional peptide.[21 23] There are a considerable number of professor in the Institute of studies taking advantage of such structural features to equip Biophysics, Chinese Academy of functional motifs on SV40 VNPs. For example, enhanced green Sciences (CAS). He became a full fluorescence protein (EGFP) was fused to the N-terminus of VP1 professor in the Wuhan Institute of to visualize the behavior of SV40 VNPs in living cell;[23] Virology, CAS in 1992, and has therapeutic Hirulog peptide was fused to the N-terminus while published 240 peer-reviewed papers targeting peptide was inserted into the HI loop or the DE loop of and three books in biosensors, VP1 for targeted treatment of atherosclerotic plaques;[22] human nanobiology, and analytical epidermal growth factor (hEGF) was chemically conjugated to microbiology. He serves as a vice the DE loop via the hetero-bifunctional crosslinker SM(PEG) for 2 chair of the Chinese Society of Biotechnology and co-chair targeting cells overexpressing the EGF receptor.[24,25] Also, the of the Division of Nanobiotechnology, Biosensors & internal proteins VP2 and VP3 can be used to fuse cargo peptides Biochips. In 2015, he was awarded an Honorary Doctor of and proteins. By encapsulating fluorescence proteins (mCherry Science Degree by the University of Alberta, Canada. or EGFP) fused to the C-terminus of VP2/3, the uptake of SV40 VNPs by cells was tracked. Using a similar strategy, yeast cytosine deaminase (yCD), a prodrug-modifying enzyme that Feng Li is currently a principal converts 5-fluorocytosine to 5-fluorouracil, was encapsulated investigator at Wuhan Institute of into SV40 VNPs. CV-1 cells became sensitive to 5-fluorocytosine- Virology (WIV), Chinese Academy of induced cell death when challenged by the yCD-encapsulating Sciences (CAS), and the deputy SV40 VNPs.[24,26] Taken together, controllable in vitro self- director of the center for analytical assembly and the capacity to load foreign peptides or proteins microbiology and nanobiology of make SV40 VNPs a useful platform for nanobiotechnological WIV. Prof. Li received his BS from applications. Shandong University in 2004 and PhD from WIV, CAS in 2009. After postdoctoral training at Suzhou 3. SV40 VNPs for Nanobiotechnological Institute of Nano-Tech and Nano-Bionics, CAS, he moved back to WIV and started independent research in 2013. Applications His research interests include integration of protein 3.1. Encapsulation of Diverse Nanoparticles nanostructures (especially virus-based nanoparticles) with chemically synthesized nanomaterials and cutting-edge SV40 VNPs have exhibited good compatibility in encapsulating applications of these hybrid nanostructures and devices nanomaterials with different components, shapes, sizes and for delivery and sensing. surface properties. A series of nanoparticles (NPs) including [22,27–33] [29,34] CdSe@ZnS quantum dots (QDs), Ag2S QDs, gold NPs (AuNPs),[29,35,36] citrate-coated magnetic NPs (MNPs)[25] have been encapsulated by SV40 VNPs through self-assembly, (Figure 2A).[35] MNPs with diameters of 8, 20, and 27 nm can with one NP core inside one VNP (Figure 2). An effort to explore also be encapsulated in SV40 VNPs, leading to 45 nm VNPs the NP-induced SV40 VNP assembly mechanism found that (Figure 2B). The C-terminal region of VP1 was found to be there was a strong affinity between QDs and SV40 VP1 critical for the complete coverage of MNPs by VP1 pentamers ¼ pentamers (KD 2.19E-10 M), which should play an important because loss of this region caused nonspecific attachment of VP1 role in driving QD encapsulation in