Viruses are parasites that infect cells and use cellular machinery to replicate. Viruses latch onto cells through their capsid, which is essentially a biological box made up of special proteins that protect the viral genome from damage and allow viruses to latch onto cells. The capsid is metastable, which means that it can disassemble in the right conditions and release the viral genome into the cell. Some viruses have miniature versions of DNA genomes like ours, but others have genomes made of RNA, which is very uncommon in nature. In the cell, viral genomes can be decoded to make messenger RNA (mRNA), which ribosomes subsequently decode into viral proteins. Some viruses have RNA genomes that bypass the first decoding step and are directly translated by ribosomes. Viral proteins can assemble into capsids that can receive newly-synthesized viral genomes. These new viruses leave the cell and latch onto other cells, repeating the infection cycle.
Viruses get a bad rap because they cause diseases popularized in the media (ex. Ebola, Zika, etc.). Virus-like particles (VLPs) mimic viruses, except they do not contain any viral DNA or RNA genomes. Instead, they are just empty shells made of protein. This means that they do not cause any infectious symptoms. However, their strong resemblance to authentic viruses means that they can be used as very safe and effective vaccines. Indeed, all three Human Papilloma Virus (HPV) vaccines are based on VLPs that trick the immune system to create antibodies that block later infection with authentic cancer-causing HPV strains. These remarkable vaccines have been available for the last decade, and there is already strong data indicating that they are greatly decreasing incidence of genital warts and cervical cancer. In fact, the Australian government has recently declared plans to eliminate cervical cancer in Australia through a comprehensive vaccination campaign. Inspired by the success of the HPV vaccines, other research groups have developed VLP-based vaccines for a variety of viruses, including the noroviruses that cause the dreaded ‘two-bucket disease’ experienced by cruise ship passengers.
Since VLPs by definition are empty boxes, scientists started dreaming up ways to fill the box with different useful cargo that can be delivered into a target cell. For example, a VLP loaded with chemotherapy drugs could be used to directly kill cancer cells. Different viruses have evolved to infect different cell types, which provides opportunities for selective targeting of different cell types for drug delivery. For example, Hepatitis B virus (HBV) infects human liver cells and causes a range of diseases that can ultimately lead to cancer. Scientists have modified HBV to create a safe nanoparticle similar to a VLP, which can be used to selectively deliver drugs into liver cells without causing disease.
VLPs are an exciting technology that takes advantage of the useful properties of viral capsids as strong and simply-assembled boxes that can disassemble following interactions with a specific cell type. As more viruses are modified to create VLPs, we may discover new applications beyond vaccines and gene delivery.
Summary written by: Emily Yang (Hawaii iGEM Team)
To read the full articles, please click the following links:
The Life-Cycle of the HIV-1 Gag–RNA Complex
Virus-like particles as vaccines and vessels for the delivery of small molecules
