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. 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.
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.
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. 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. More recently, VLPs have been used to develop a pre-clinical vaccine against chikungunya virus.
Research suggests that VLP vaccines against influenza virus could provide stronger and longer-lasting protection against flu viruses than conventional vaccines. 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. Novavax and Medicago Inc. have both run clinical trials of their VLP flu vaccines.
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.
Recently, a specialized VLP, called the ‘Lipoparticle’, has been developed to aid the study of integral membrane proteins. 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. 
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. Study also reals that in vitro assembly of VLPs competes with aggregation, and some believe that certain mechanism exists inside the cell to prevent the formation of aggregates while assembly is ongoing.
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