Virus-like particle

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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 proteins, 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]


Virus research[edit]

VLPs are used in studies to identify viral protein components.

Therapeutic and Imaging Agents[edit]

VLPs are a candidate delivery system for genes or other therapeutics.[3] These drug delivery agents have been shown to effectively target cancer cells in vitro.[4] It is hypothesized that VLPs may accumulate in tumor sites due to the enhanced permeability and retention effect, which could be useful for drug delivery or tumor imaging [5]


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.[6] 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.[7] More recently, VLPs were used to develop a pre-clinical vaccine against chikungunya virus.[6]

Research suggests that VLP vaccines against influenza virus could provide stronger and longer-lasting protection against flu viruses than conventional vaccines.[8] 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.[9] Novavax and Medicago Inc. have run clinical trials of their VLP flu vaccines.[10][11]


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.[citation needed]

Lipoparticle technology[edit]

The VLP Lipoparticle was developed to aid the study of integral membrane proteins.[12] 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.[13] [14]


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.[15] Study also reveals that in vitro assembly of VLPs competes with aggregation[16] and certain mechanisms exist inside the cell to prevent the formation of aggregates while assembly is ongoing.[17]

Linking targeting groups to VLP surfaces[edit]

Attaching proteins, nucleic acids, or small molecules to the VLP surface, such as for targeting a specific cell type or for raising an immune response is useful. In some cases a protein of interest can be genetically fused to the viral coat protein.[18] However, this approach sometimes leads to impaired VLP assembly and has limited utility if the targeting agent is not protein-based. An alternative is to assemble the VLP and then use chemical crosslinkers,[19] reactive unnatural amino acids[20] or SpyTag/SpyCatcher reaction[21][22] in order to covalently attach the molecule of interest. This method has shown to be very effective at directing the immune response against the attached molecule, thereby inducing high levels of neutralizing antibody titers and breaking immune self-tolerance.[22]


  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.
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  4. ^ Galaway, F. A. & Stockley, P. G. MS2 viruslike particles: A robust, semisynthetic targeted drug delivery platform. Mol. Pharm. 10, 59–68 (2013).
  5. ^ Kovacs, E. W. et al. Dual-surface-modified bacteriophage MS2 as an ideal scaffold for a viral capsid-based drug delivery system. Bioconjug. Chem. 18, 1140–1147 (2007).
  6. ^ 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.
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  8. ^ "Creating a Mutant Strain of Streptococcus Free of All Integrated Viruses" (Press release). American Society for Microbiology. May 27, 2010. Retrieved June 8, 2010.
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  10. ^ John Gever (12 September 2010). "ICAAC: High Antibody Titers Seen With Novel Flu Vaccine".
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