Virus-like particle

Virus-like particles resemble viruses, but are non-infectious because they contain no viral genetic material. The expression of viral structural proteins, such as Envelope or Capsid, can result in the self-assembly of virus like particles (VLPs). VLPs derived from the Hepatitis B virus and composed of the small HBV derived surface antigen (HBsAg) were described in 1968 from patient sera.[1] VLPs have been produced from components of a wide variety of virus families including Parvoviridae (e.g. adeno-associated virus), Retroviridae (e.g. HIV), Flaviviridae (e.g. Hepatitis C virus) and bacteriophages (e.g. Qβ, AP205). VLPs can be produced in multiple cell culture systems including bacteria, mammalian cell lines, insect cell lines, yeast and plant cells.[2]

Applications

Virus research

VLPs are used in studies to identify viarl protein components.

Gene therapy

VLPs are a candidate delivery system for genes or other therapeutics.[3]

Vaccines

VLPs are useful as vaccines. VLPs contain repetitive, high density displays of viral surface proteins that present conformational viral epitopes that can elicit strong T cell and B cell immune responses.[4] Since VLPs cannot replicate, they provide a safer alternative to attenuated viruses. VLPs were used to develop FDA-approved vaccines for Hepatitis B and human papillomavirus.[5] More recently, VLPs were used to develop a pre-clinical vaccine against chikungunya virus.[4]

Research suggests that VLP vaccines against influenza virus could provide stronger and longer-lasting protection against flu viruses than conventional vaccines.[6] Production can begin as soon as the virus strain is sequenced and can take as little as 12 weeks, compared to 9 months for traditional vaccines. In early clinical trials, VLP vaccines for influenza appeared to provide complete protection against both the Influenza A virus subtype H5N1 and the 1918 flu pandemic.[7] Novavax and Medicago Inc. have run clinical trials of their VLP flu vaccines.[8][9]

Mycoviruses

Some fungi contain mycoviruses that lack the ability to be transmitted in cell free preparations and may be classified as VLPs. These are important in phytopathology, as they can cause hypovirulence in some species of phytopathogenic fungi.

Lipoparticle technology

The VLP Lipoparticle was developed to aid the study of integral membrane proteins.[10] Lipoparticles are stable, highly purified, homogeneous VLPs that are engineered to contain high concentrations of a conformationally intact membrane protein of interest. Integral Membrane proteins are involved in diverse biological functions and are targeted by nearly 50% of existing therapeutic drugs. However, because of their hydrophobic domains, membrane proteins are difficult to manipulate outside of living cells. Lipoparticles can incorporate a wide variety of structurally intact membrane proteins, including G protein-coupled receptors (GPCR)s, ion channels and viral Envelopes. Lipoparticles provide a platform for numerous applications including antibody screening, production of immunogens and ligand binding assays.[11] [12]

Assembly

The understanding of self-assembly of VLPs was once based on viral assembly. This is rational as long as the VLP assembly takes place inside the host cell (in vivo), though the self-assembly event was found in vitro from the very beginning of the study about viral assembly.[13] Study also reveals that in vitro assembly of VLPs competes with aggregation[14] and certain mechanisms exist inside the cell to prevent the formation of aggregates while assembly is ongoing.[15]

Linking proteins to VLP surfaces

Attaching proteins to the VLP surface, such as for targeting a specific cell type or for raising an immune response is useful. In some cases the protein of interest can be genetically fused to the viral coat protein but this approach sometimes leads to impaired VLP assembly. An alternative is to assemble the VLP and then use chemical crosslinkers,[16] reactive unnatural amino acids[17] or SpyTag/SpyCatcher reaction[18] to covalently attach the protein of interest.

References

  1. ↑ Bayer ME, Blumberg BS, Werner B (June 1968). "Particles associated with Australia antigen in the sera of patients with leukaemia, Down's Syndrome and hepatitis". Nature 218 (5146): 1057–9. doi:10.1038/2181057a0. PMID 4231935.
  2. ↑ Santi L, Huang Z, Mason H (September 2006). "Virus like particles production in green plants". Methods 40 (1): 66–76. doi:10.1016/j.ymeth.2006.05.020. PMC 2677071. PMID 16997715.
  3. ↑ Petry H, Goldmann C, Ast O, Lüke W (October 2003). "The use of virus-like particles for gene transfer". Current Opinion in Molecular Therapeutics 5 (5): 524–8. PMID 14601522.
  4. 1 2 Akahata W, Yang ZY, Andersen H, et al. (March 2010). "A VLP vaccine for epidemic Chikungunya virus protects non-human primates against infection". Nature Medicine 16 (3): 334–8. doi:10.1038/nm.2105. PMC 2834826. PMID 20111039.
  5. ↑ Zhang X, Xin L, Li S, Fang M, Zhang J, Xia N, Zhao Q. (2015). "Lessons learned from successful human vaccines: Delineating key epitopes by dissecting the capsid proteins". Human Vacc Immunother 11 (5): 1277. doi:10.1080/21645515.2015.1016675. PMC 4514273. PMID 25751641.
  6. ↑ "Creating a Mutant Strain of Streptococcus Free of All Integrated Viruses" (Press release). American Society for Microbiology. May 27, 2010. Retrieved June 8, 2010.
  7. ↑ Perrone, L. A.; Ahmad, A.; Veguilla, V.; Lu, X.; Smith, G.; Katz, J. M.; Pushko, P.; Tumpey, T. M. (25 March 2009). "Intranasal Vaccination with 1918 Influenza Virus-Like Particles Protects Mice and Ferrets from Lethal 1918 and H5N1 Influenza Virus Challenge". Journal of Virology 83 (11): 5726–5734. doi:10.1128/JVI.00207-09.
  8. ↑ John Gever (12 September 2010). "ICAAC: High Antibody Titers Seen With Novel Flu Vaccine".
  9. ↑ Landry, N; Ward, BJ; Trépanier, S; Montomoli, E; Dargis, M; Lapini, G; Vézina, LP (2010). Fouchier, Ron A. M., ed. "Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza". PLoS ONE 5 (12): e15559. doi:10.1371/journal.pone.0015559. PMC 3008737. PMID 21203523.
  10. ↑ "Integral Molecular" (PDF).
  11. ↑ Willis S, Davidoff C, Schilling J, Wanless A, Doranz BJ, Rucker J (July 2008). "Use of virus-like particles as quantitative probes of membrane protein interactions". Biochemistry 47 (27): 6988–90. doi:10.1021/bi800540b. PMC 2741162. PMID 18553929.
  12. ↑ Jones JW, Greene TA, Grygon CA, Doranz BJ, Brown MP (June 2008). "Cell-free assay of G-protein-coupled receptors using fluorescence polarization". Journal of Biomolecular Screening 13 (5): 424–9. doi:10.1177/1087057108318332. PMID 18567842.
  13. ↑ Adolph KW, Butler PJG (November 1976). "Assembly of a spherical plant-virus". Philosophical Transactions of the Royal Society B 276 (943): 113–. doi:10.1098/rstb.1976.0102.
  14. ↑ Ding Y, Chuan YP, He LZ, Middelberg APJ (October 2010). "Modeling the competition between aggregation and self-assembly during virus-like particle processing". Biotechnology and Bioengineering 107 (3): 550–560. doi:10.1002/bit.22821. PMID 20521301.
  15. ↑ Chromy LR, Pipas JM, Garcea RL (September 2003). "Chaperone-mediated in vitro assembly of Polyomavirus capsids". Proceedings of the National Academy of Sciences of the United States of America 100 (18): 10477–10482. doi:10.1073/pnas.1832245100. PMC 193586. PMID 12928495.
  16. ↑ Jegerlehner A, Tissot A, Lechner F, Sebbel P, Erdmann I, Kündig T, Bächi T, Storni T, Jennings G, Pumpens P, Renner WA, Bachmann MF. (2002). "A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses". Vaccine 20: 3104. doi:10.1016/S0264-410X(02)00266-9. PMID 12163261.
  17. ↑ Patel KG, Swartz JR. (2011). "Surface functionalization of virus-like particles by direct conjugation using azide-alkyne click chemistry". Bioconj Chem 22: 376. doi:10.1021/bc100367u. PMID 21355575.
  18. ↑ Brune KD, Leneghan DB, Brian IJ, Ishizuka AS, Bachmann MF, Draper SJ, Biswas S, Howarth M. (2016). "Plug-and-Display: decoration of Virus-Like Particles via isopeptide bonds for modular immunization". Sci Rep 6: 19234. doi:10.1038/srep19234. PMID 26781591.

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