Production of recombinant VP1-derived virus-like particles from novel human polyomaviruses in yeast

BMC Biotechnology

Milda Norkiene¹  Jomante Stonyte¹  Danguole Ziogiene¹  Egle Mazeike¹  Kestutis Sasnauskas¹  Alma Gedvilaite¹ 

[1] Institute of Biotechnology, Vilnius University, Graiciuno 8, Vilnius, LT-02241, Lithuania

关键词: Hemagglutination assay;    Yeast;    Virus-like particles;    VP1;    Human polyomavirus;   

Others  :  1223715
DOI  :  10.1186/s12896-015-0187-z

 received in 2015-01-12, accepted in 2015-07-24,  发布年份 2015

【 摘 要 】

Background

Eleven new human polyomaviruses (HPyVs) have been identified in the last decade. Serological studies show that these novel HPyVs sub-clinically infect humans at an early age. The routes of infection, entry pathways, and cell tropism of new HPyVs remain unknown. VP1 proteins of polyomaviruses can assembly into virus-like particles (VLPs). As cell culturing systems for HPyV are currently not available, VP1-derived VLPs may be useful tools in basic research and biotechnological applications.

Results

Recombinant VP1-derived VLPs from 11 newly identified HPyVs were efficiently expressed in yeast. VP1 proteins derived from Merkel cell polyomavirus (MCPyV), trichodysplasia spinulosa-associated polyomavirus (TSPyV), and New Jersey polyomavirus (NJPyV) self-assembled into homogeneous similarly-sized VLPs. Karolinska Institutet polyomavirus (KIPyV), HPyV7, HPyV9, HPyV10, and St. Louis polyomavirus (STLPyV) VP1 proteins formed VLPs that varied in size with diameters ranging from 20 to 60 nm. Smaller-sized VLPs (25–35 nm in diameter) predominated in preparations from Washington University polyomavirus (WUPyV) and HPyV6. Attempts to express recombinant HPyV12 VP1-derived VLPs in yeast indicate that translation of VP1 might start at the second of two potential translation initiation sites in the VP1-encoding open reading frame (ORF). This translation resulted in a 364-amino acid-long VP1 protein, which efficiently self-assembled into typical PyV VLPs. MCPyV-, KIPyV-, TSPyV-, HPyV9-, HPyV10-, and HPyV12-derived VLPs showed hemagglutination (HA) assay activity in guinea pig erythrocytes, whereas WUPyV-, HPyV6-, HPyV7-, STLPyV- and NJPyV-derived VP1 VLPs did not.

Conclusions

The yeast expression system was successfully utilized for high-throughput production of recombinant VP1-derived VLPs from 11 newly identified HPyVs. HPyV12 VP1-derived VLPs were generated from the second of two potential translation initiation sites in the VP1-encoding ORF. Recombinant VLPs produced in yeast originated from different HPyVs demonstrated distinct HA activities and may be useful in virus diagnostics, capsid structure studies, or investigation of entry pathways and cell tropism of HPyVs until cell culture systems for new HPyVs are developed.

【 授权许可】

   
2015 Norkiene et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig. 4.

Figure 1.

Fig. 6.

【 参考文献 】

• [1]Imperiale MJ, Major EO. Polyomaviruses. In: Fields virology. Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, Straus SE, editors. Lippincott Williams and Wilkins, Philadelphia; 2007: p.2263-98.
• [2]Feltkamp MC, Kazem S, van der Meijden E, Lauber C, Gorbalenya AE. From Stockholm to Malawi: recent developments in studying human polyomaviruses. J Gen Virol. 2013; 94:482-96.
• [3]Johne R, Buck CB, Allander T, Atwood WJ, Garcea RL, Imperiale MJ et al.. Taxonomical developments in the family Polyomaviridae. Arch Virol. 2011; 156:1627-34.
• [4]Stewart SE, Eddy BE, Borgese NG. Neoplasms in mice inoculated with a tumor agent carried in tissue culture. J Natl Cancer Inst. 1958; 20:1223-43.
• [5]Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet. 1971; 1(7712):1253-7.
• [6]Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971; 1(7712):1257-60.
• [7]Allander T, Andreasson K, Gupta S, Bjerkner A, Bogdanovic G, Persson MA et al.. Identification of a third human polyomavirus. J Virol. 2007; 81(8):4130-6.
• [8]Gaynor AM, Nissen MD, Whiley DM, Mackay IM, Lambert SB, Wu G et al.. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog. 2007; 3(5): Article ID e64
• [9]Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008; 319(5866):1096-100.
• [10]Schowalter RM, Pastrana DV, Pumphrey KA, Moyer AL, Buck CB. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe. 2010; 7(6):509-15.
• [11]van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Pathog. 2010; 6: Article ID e1001024
• [12]Scuda N, Hofmann J, Calvignac-Spencer S, Ruprecht K, Liman P, Kühn J et al.. A novel human polyomavirus closely related to the african green monkey-derived lymphotropic polyomavirus. J Virol. 2011; 85:4586-90.
• [13]Buck CB, Phan GQ, Raiji MT, Murphy PM, McDermott DH, McBride AA. Complete genome sequence of a tenth human polyomavirus. J Virol. 2012; 86(19):10887.
• [14]Lim ES, Reyes A, Antonio M, Saha D, Ikumapayi UN, Adeyemi M et al.. Discovery of STL polyomavirus, a polyomavirus of ancestral recombinant origin that encodes a unique T antigen by alternative splicing. Virology. 2013; 436(2):295-303.
• [15]Korup S, Rietscher J, Calvignac-Spencer S, Trusch F, Hofmann J, Moens U et al.. Identification of a novel human polyomavirus in organs of the gastrointestinal tract. PLoS One. 2013; 8(3): Article ID e58021
• [16]Siebrasse EA, Reyes A, Lim ES, Zhao G, Mkakosya RS, Manary MJ et al.. Identification of MW polyomavirus, a novel polyomavirus in human stool. J Virol. 2012; 86(19):10321-6.
• [17]Yu G, Greninger AL, Isa P, Phan TG, Martinez MA, de la Luz Sanchez M et al.. Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS One. 2012; 7(11): Article ID e49449
• [18]Mishra N, Pereira M, Rhodes RH, An P, Pipas J, Jain K et al.. Identification of a novel polyomavirus in a pancreatic transplant recipient with retinal blindness and vasculitic myopathy. J Infect Dis. 2014; 210(10):1595-9.
• [19]Dalianis T, Hirsch HH. Human polyomaviruses in disease and cancer. Virology. 2013; 437(2):63-72.
• [20]Moens U, Van Ghelue M, Song X, Ehlers B. Serological cross-reactivity between human polyomaviruses. Rev Med Virol. 2013; 23:250-64.
• [21]Knowles WA. Serendipity – the discovery of BK virus. In: Human polyomaviruses: molecular and clinical perspectives. Khalili K, Stoner GL, editors. Wiley-Liss, Inc, New York; 2001: p.45-52.
• [22]Pinto M, Dobson S. BK and JC virus: a review. J Infect. 2014; 68 Suppl 1:S2-8.
• [23]Ferenczy MW, Marshall LJ, Nelson CD, Atwood WJ, Nath A, Khalili K et al.. Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev. 2012; 25:471-506.
• [24]Ho J, Jedrych JJ, Feng H, Natalie AA, Grandinetti L, Mirvish E, et al. Human polyomavirus 7-associated pruritic rash and viremia in transplant recipients. J Infect Dis. 2014. doi:. 10. 1093/infdis/jiu524 webcite
• [25]Munoz LJ, Ludena D, Gedvilaite A, Zvirbliene A, Jandrig B, Voronkova T et al.. Lymphoma outbreak in a GASH:Sal hamster colony. Arch Virol. 2013; 158(11):2255-65.
• [26]Cheng J, DeCaprio JA, Fluck MM, Schaffhausen BS. Cellular transformation by Simian Virus 40 and Murine Polyoma Virus Tantigens. Semin Cancer Biol. 2009; 19(4):218-28.
• [27]Shen PS, Enderlein D, Nelson CD, Carter WS, Kawano M, Xing L, Swenson RD et al.. The structure of avian polyomavirus reveals variably sized capsids, nonconserved inter-capsomere interactions, and a possible location of the minor capsid protein VP4. Virology. 2011; 411:142-52.
• [28]Salunke DM, Caspar DL, Garcea RL. Self-assembly of purified polyomavirus capsid protein VP1. Cell. 1986; 46:895-904.
• [29]Sasnauskas K, Buzaite O, Vogel F, Jandrig B, Razanskas R, Staniulis J et al.. Yeast cells allow the high-level expression and formation of polyomavirus-like particles. Biol Chem. 1999; 380:381-6.
• [30]Sasnauskas K, Bulavaite A, Hale A, Jin L, Gedvilaite A, Dargeviciute A et al.. Generation of recombinant virus-like particles of human and non-human polyomaviruses in yeast Saccharomyces cerevisiae. Intervirology. 2002; 45:471-82.
• [31]Teunissen EA, de Raad M, Mastrobattista E. Production and biomedical applications of virus-like particles derived from polyomaviruses. J Control Release. 2013; 172(1):305-21.
• [32]Nelson CD, Derdowski A, Maginnis MS, O’Hara BA, Atwood WJ. The VP1 subunit of JC polyomavirus recapitulates early events in viral trafficking and is a novel tool to study polyomavirus entry. Virology. 2012; 428(1):30-40.
• [33]Nicol JT, Robinot R, Carpentier A, Carandina G, Mazzoni E, Tognon M et al.. Age-specific seroprevalences of merkel cell polyomavirus, human polyomaviruses 6, 7, and 9, and trichodysplasia spinulosa-associated polyomavirus. Clin Vaccine Immunol. 2013; 20(3):363-8.
• [34]Nicol JT, Leblond V, Arnold F, Guerra G, Mazzoni E, Tognon M et al.. Seroprevalence of Human Malawi Polyomavirus. J Clin Microbiol. 2014; 52(1):321-3.
• [35]Norkiene M, Gedvilaite A. Influence of codon bias on heterologous production of human papillomavirus type 16 major structural protein L1 in yeast. Sci World J. 2012; 2012:979218.
• [36]Angov E, Hillier CJ, Kincaid RL, Lyon JA. Heterologous protein expression is enhanced by harmonizing the codon usage frequencies of the target gene with those of the expression host. PLoS One. 2008; 3(5): Article ID e2189
• [37]Rodgers RE, Chang D, Cai X, Consigli RA. Purification of recombinant budgerigar fledgling disease virus VP1 capsid protein and its ability for in vitro capsid assembly. J Virol. 1994; 68(5):3386-90.
• [38]Knowles WA, Pipkin P, Andrews N, Vyse A, Minor P, Brown DW et al.. Population-based study of antibody to the human polyomaviruses BKVand JCV and the simian polyomavirus SV40. J Med Virol. 2003; 71:15-123.
• [39]Erickson KD, Garcea RL, Tsai B. Ganglioside GT1b is a putative host cell receptor for the Merkel cell polyomavirus. J Virol. 2009; 83(19):10275-9.
• [40]Ou WC, Wang M, Fung CY, Tsai RT, Chao PC, Hseu TH et al.. The major capsid protein, VP1, of human JC virus expressed in Escherichia coli is able to self-assemble into a capsid-like particle and deliver exogenous DNA into human kidney cells. J Gen Virol. 1999; 80:39-46.
• [41]Voronkova T, Kazaks A, Ose V, Ozel M, Scherneck S, Pumpens P et al.. Hamster polyomavirus-derived virus-like particles are able to transfer in vitro encapsidated plasmid DNA to mammalian cells. Virus Genes. 2007; 34:303-14.
• [42]Liew MW, Rajendran A, Middelberg AP. Microbial production of virus-like particle vaccine protein at gram-per-litre levels. J Biotechnol. 2010; 150(2):224-31.
• [43]Middelberg AP, Rivera-Hernandez T, Wibowo N, Lua LH, Fan Y, Magor G et al.. A microbial platform for rapid and low-cost virus-like particle and capsomere vaccines. Vaccine. 2011; 29(41):7154-62.
• [44]Liew MW, Chuan YP, Middelberg AP. High-yield and scalable cell-free assembly of virus-like particles by dilution. Biochem Eng J. 2012; 67:88-96.
• [45]Simon C, Klose T, Herbst S, Han BG, Sinz A, Glaeser RM et al.. Disulfide linkage and structure of highly stable yeast-derived virus-like particles of murine polyomavirus. J Biol Chem. 2014; 289:10411-8.
• [46]Kean JM, Rao S, Wang M, Garcea RL. Seroepidemiology of human polyomaviruses. PLoS Pathog. 2009; 5(3): Article ID e1000363
• [47]van der Meijden E, Kazem S, Burgers MM, Janssens R, Bouwes Bavinck JN, de Melker H et al.. Seroprevalence of Trichodysplasia Spinulosa–associated Polyomavirus. Emerg Infect Dis. 2011; 17(8):1355-63.
• [48]Pastrana DV, Tolstov YL, Becker JC, Moore PS, Chang Y, Buck CB. Quantitation of human seroresponsiveness to Merkel cell polyomavirus. PLoS Pathog. 2009; 5(9): Article ID e1000578
• [49]Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S et al.. Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays. Int J Cancer. 2009; 125:1250-6.
• [50]Touze A, Gaitan J, Arnold F, Cazal R, Fleury MJ, Combelas N et al.. Generation of Merkel cell polyomavirus (MCV)-like particles and their application to detection of MCV antibodies. J Clin Microbiol. 2010; 48:1767-70.
• [51]Kumar A, Kantele A, Jarvinen T, Chen T, Kavola H, Sadeghi M et al.. Trichodysplasia spinulosa-associated polyomavirus (TSV) and Merkel cell polyomavirus: correlation between humoral and cellular immunity stronger with TSV. PLoS One. 2012; 7(9): Article ID e45773
• [52]Canganella F, Paganini S, Ovidi M, Vettraino AM, Bevilacqua L, Massa S et al.. A microbiology investigation on probiotic pharmaceutical products used for human health. Microbiol Res. 1997; 152:171-9.
• [53]Garrait G, Jarrige JF, Blanquet S, Beyssac E, Alric M. Recombinant Saccharomyces cerevisiae strain expressing a model cytochrome P450 in the rat digestive environment: viability and bioconversion activity. Appl Environ Microbiol. 2007; 73:3566-74.
• [54]Villa LL, Costa RL, Petta CA, Andrade RP, Ault KA, Giuliano AR et al.. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol. 2005; 6:271-8.
• [55]Kler S, Wang JC, Dhason M, Oppenheim A, Zlotnick A. Scaffold properties are a key determinant of the size and shape of self-assembled virus-derived particles. ACS Chem Biol. 2013; 8(12):2753-61.
• [56]Salunke DM, Caspar DL, Garcea RL. Polymorphism in the assembly of polyomavirus capsid protein VP1. Biophys J. 1989; 56:887-900.
• [57]Stehle T, Harrison S. Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragment. Structure. 1996; 4:183-94.
• [58]Rayment I, Baker TS, Caspar DL, Murakami WT. Polyoma virus capsid structure at 22.5 A resolution. Nature. 1982; 295:110-5.
• [59]Nilsson J, Miyazaki N, Xing L, Wu B, Hammar L, Li TC et al.. Structure and assembly of a T = 1 virus-like particle in BK polyomavirus. J Virol. 2005; 79:5337-45.
• [60]Gedvilaite A, Aleksaite E, Staniulis J, Ulrich R, Sasnauskas K. Size and position of truncations at the carboxy-terminal region of major capsid protein VP1 of hamster polyomavirus expressed in yeast determine its assembly capacity. Arch Virology. 2006; 151(9):1811-25.
• [61]Siray H, Ozel M, Jandrig B, Voronkova T, Jia W, Zocher R et al.. Capsid protein-encoding genes of hamster polyomavirus and properties of the viral capsid. Virus Genes. 1999; 18(1):39-47.
• [62]Knowles WA, Sasnauskas K. Comparison of cell culture-grown JC virus (primary human fetal glial cells and the JCI cell line) and recombinant JCV VP1 as antigen for the detection of anti-JCV antibody by haemagglutination inhibition. J Virol Methods. 2003; 109(1):47-54.
• [63]O’Hara SD, Stehle T, Garcea R. Glycan receptors of the Polyomaviridae: structure, function, and pathogenesis. Curr Opin Virol. 2014; 7:73-8.
• [64]Maginnis MS, Nelson CD, Atwood WJ. JC polyomavirus attachment, entry, and trafficking: unlocking the keys to a fatal infection. J Neurovirol. 2014. [Epub ahead of print].
• [65]Stehle T, Yan Y, Benjamin TL, Harrison SC. Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment. Nature. 1994; 369(6476):160-3.
• [66]Breau WC, Atwood WJ, Norkin LC. Class I major histocompatibility proteins are an essential component of the simian virus 40 receptor. J Virol. 1992; 66(4):2037-45.
• [67]Neu U, Woellner K, Gauglitz G, Stehle T. Structural basis of GM1 ganglioside recognition by simian virus 40. Proc Natl Acad Sci U S A. 2008; 105:5219-24.
• [68]Ewers H, Romer W, Smith AE, Bacia K, Dmitrieff S, Chai W et al.. GM1 structure determines SV40-induced membrane invagination and infection. Nat Cell Biol. 2010; 12(1):11-8.
• [69]Magaldi TG, Buch MH, Murata H, Erickson KD, Neu U, Garcea RL et al.. Mutations in the GM1 binding site of simian virus 40 VP1 alter receptor usage and cell tropism. J Virol. 2012; 86:7028-42.
• [70]Neu U, Hengel H, Blaum BS, Schowalter RM, Macejak D, Gilbert M et al.. Structures of Merkel cell polyomavirus VP1 complexes define a sialic acid binding site required for infection. PLoS Pathog. 2012; 8(7): Article ID e1002738
• [71]Khan ZM, Liu Y, Neu U, Gilbert M, Ehlers B, Feizi T et al.. Crystallographic and glycan microarray analysis of human polyomavirus 9 VP1 identifies N-glycolyl neuraminic acid as a receptor candidate. J Virol. 2014; 88(11):6100-11.
• [72]Stroh LJ, Neu U, Blaum BS, Buch MH, Garcea RL, Stehle T. Structure analysis of the major capsid proteins of human polyomaviruses 6 and 7 reveals an obstructed sialic acid binding site. J Virol. 2014; 88(18):10831-9.
• [73]Neu U, Wang J, Macejak D, Garcea RL, Stehle T. Structures of the major capsid proteins of the human Karolinska Institutet and Washington University polyomaviruses. J Virol. 2011; 85:7384-92.
• [74]Sambrook J, Russell DW. Molecular cloning, a laboratory manual. Cold Spring Harbor Press, Cold Spring Harbour; 2001.
• [75]Pleckaityte M, Zvirbliene A, Sezaite I, Gedvilaite A. Production in yeast of pseudotype virus-like particles harboring functionally active antibody fragments neutralizing the cytolytic activity of vaginolysin. Microb Cell Fact. 2011; 10:109. BioMed Central Full Text