In a ground breaking study in the UK researchers have identified a previously unknown mechanism that allows the immune system to fight viruses even after they have infected cells. Until now it was believed that antibodies can act only before the virus enters the cells. The team now has found that antibodies that attached themselves to a virus were able to follow it into cells and help to destroy the virus before it started to reproduce. This could open up new avenues of therapy.
The study was conducted by the researchers from the Laboratory of Molecular Biology in Cambridge and the Centre for Medical Molecular Virology in London, which are both funded by the Medical Research Council. It is soon to be published in the peer-reviewed scientific and medical journal Proceedings of the National Academy of Sciences of the USA.
For this study the team examined how viruses invade cells and how antibodies are involved in immune response that follows. Antibodies are small molecules in the immune system that attach to invading pathogens (bacteria and viruses) to help the body fight infection. The study focused on adenovirus, which can cause respiratory infections but not the ‘common cold’, although it can cause cold-like symptoms. The study did not involve any people or animals.
The scientists already knew of a protein called ‘tripartite motif-containing 21’ (TRIM21) that could bind to antibody molecules. However, TRIM21 is found inside cells and antibodies are usually found outside. To see whether antibodies come into contact with TRIM21 inside cells, the researchers took adenoviruses and coated them in antibodies. Then they introduced the viruses into cell lines that have the ability to continue growing in the laboratory. Using fluorescent dyes, they could see whether the antibodies also entered the cells and if TRIM21 was able to bind to them. They also tested how TRIM21 interacts with other immune system molecules and how it helps to degrade viruses once they enter cells.
The results showed that adenoviruses coated in antibodies were able to enter cells and it was here that they attracted TRIM21 molecules. Within cells, TRIM21 and antibodies acted to help the immune system fight the virus.
This, say researchers shows that “humoral immunity is not limited to extracellular protection but can neutralise a virus even after it has entered a cell.” They also report that the way in which TRIM21 helps the immune system “offers the possibility of ‘curing’ rather than killing an infected cell” due to the speed with which it neutralizes the virus before it has had the chance to replicate itself. The researchers noted that TRIM21 is found in most kinds of cell and not just in specialized immune cells.
Professor Earl Brown, a virologist at the University of Ottawa feels, “It's very hopeful for creating new vaccines, or for treating infections…over a period of decades, this will filter out to the clinic, where it will be applied.” Lead researcher Dr. Leo James and his team could take a decade to make this a reality in terms of therapy.
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