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Virus-like particle

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Virus-like particles resemble viruses, but are non-infectious because they do not contain any 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 over 40 years ago from patient sera.[1] More recently, VLPs have been produced from components of a wide variety of virus families including Parvoviridae (e.g. adeno-associated virus), Retroviridae (e.g. HIV), and Flaviviridae (e.g. Hepatitis C virus). VLPs can be produced in a variety of cell culture systems including mammalian cell lines, insect cell lines, yeast, and plant cells.[2]

Applications of VLPs

Virus research
VLPs are often used in studies to identify protein components required for viral assembly.
Gene therapy
efforts are focused on utilizing VLPs as a delivery system for genes or other therapeutics.[3]

Vaccines

VLPs are a useful tool for the development of vaccines. VLPs contain repetitive high density displays of viral surface proteins which present conformational viral epitopes that can elicit strong T cell and B cell immune responses.[4] Additionally, since VLPs lack genetic material, they provide a safer alternative to attenuated viruses. VLPs have already been used to develop FDA approved vaccines for Hepatitis B and human papillomavirus.[citation needed] More recently, VLPs have been used to develop a pre-clinical vaccine against chikungunya virus.[4]

Influenza vaccines

Research suggests that VLP vaccines against influenza virus could provide stronger and longer lasting protection against flu viruses than conventional vaccines.[5] Production may begin as soon as the genetic sequence of the virus strain becomes available and it may 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.Journal of Virology Novavax and Medicago Inc. have both run clinical trials of their VLP flu vaccines.[6][7]

Mycovirus VLPs

Some fungi contain mycoviruses that lack the ability to be transmitted in cell free preparations and may be classified as virus like particles. These VLPs are important in phytopathology, as they have been shown to cause hypovirulence in some species of phytopathogenic fungi.[citation needed]

Lipoparticle Technology

Recently, a specialized VLP, called the ‘Lipoparticle’, has been developed to aid the study of integral membrane proteins.[8] 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.[9] [10]

Assembly of VLPs

Previously, the understanding of self-assembly of VLPs was 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.[11] Study also reals that in vitro assembly of VLPs competes with aggregation,[12] and some believe certain mechanism exist inside the cell to prevent the formation of aggregates while assembly is ongoing.[13]

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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b 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. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  5. ^ "Creating a Mutant Strain of Streptococcus Free of All Integrated Viruses" (Press release). American Society for Microbiology. May 27, 2010. Retrieved June 8, 2010.
  6. ^ http://www.medpagetoday.com/MeetingCoverage/ICAAC/22129
  7. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  8. ^ Lipoparticle Application Note
  9. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. ^ 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.
  12. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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