Key clue to fighting viruses

crabsallover says 'a spectacular jump in our level of understanding of how viruses infect us. Proteosomes are the final molecule IN the cell that destroys the virus. View the video.'

reposted from:  NHS

NHS Choices Tue Nov 02 2010 10:25:00 GMT+0000 (GMT Standard Time) Share

view 8 photos showing attachment of antibodies to virus WITHIN the cell

A cure for the common cold may be on the way after “a remarkable discovery in a Cambridge laboratory”, The Independent has reported. The newspaper said that new research has identified a previously unkown mechanism that allows the immune system to fight viruses even after they have infected cells.

In the study, researchers 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 is in contrast to the previous understanding that antibodies did not enter cells and were only effective at fighting infection before viruses invade cells.

This study provides an interesting insight into how viruses and antibodies behave in the body, and uncovers mechanisms that could be targeted by future treatments or therapies. It is not known, however, how quickly or successfully this knowledge will result in remedies or treatments becoming available. This would require development and testing of new drugs, an uncertain process that usually takes a number of years.

Where did the story come from?

The study was carried out by 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.

The story was reported in a variety of ways by the newspapers. The Guardian’s coverage focused on the way in which the discovery may enable new strategies for fighting infections, while other newspapers made bolder claims about any potential new treatments based on this knowledge being available within a few years. TheDaily Mirror’s statement that “colds can be cleared up days faster with a simple nasal spray”, was not supported by the findings of the study.

The original research paper makes no claims as to the potential medical benefits of the discovery so the origin of such claims about the potential uses of this knowledge is unclear. However, press coverage has generally made it clear that this was exploratory lab research in isolated cells and explained the way that viruses affect the body.

What kind of research was this?

Viruses are tiny infectious particles that can cause a number of different illnesses, including influenza, hepatitis, chickenpox and the common cold. However, unlike bacteria, they do not have the ability to replicate outside of cells, but instead replicate by entering cells and taking them over, making them produce more viral particles that can then spread and infect other cells.

In this laboratory study, the researchers 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.

It had previously been thought that antibodies do not enter cells, and are therefore only effective against viruses if they can reach the virus before it invades a cell. This study demonstrated that this is not always the case.

In order for this discovery to lead to a ‘cure for the common cold’, the researchers would need to check whether the same process was true for other respiratory viruses. It would then be necessary to develop new drugs that would need to be tested in clinical trials. This process is likely to take a number of years.

What did the research involve?

It was already known that a protein called ‘tripartite motif-containing 21’ (TRIM21) 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.

The researchers undertook further experiments to explore the role of TRIM21 in helping the immune system fight viruses once they had invaded cells. They also tested how TRIM21 interacts with other immune system molecules and how it helps to degrade viruses once they enter cells.

What were the basic results?

The researchers found 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. They found that TRIM21 helped neutralise the viruses, which were then degraded by processes inside the cell. This happened quickly, which meant that the virus was neutralised before it had even had the chance to trigger the replication process in the cell it had infected.

The way in which TRIM21 works inside a cell was found to be different to other immune system mechanisms, as it enables cells to kill a virus without needing external help from specialist immune system cells.

How did the researchers interpret the results?

The researchers say their results show that “humoral immunity is not limited to extracellular protection but can neutralise a virus even after it has entered a cell.” This means that the part of the immune system that uses antibodies as a line of defence is active inside of cells as well as outside. This goes against previous thinking, as antibody-based defences were only believed to operate outside of cells.

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 neutralises 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 specialised immune cells.

Conclusion

This study reports an interesting development in understanding of the role that antibodies play in helping the body to fight viral infections. When considering the likelihood of this leading to a ‘cure for the common cold’, it should be noted that:

• This was a laboratory study undertaken in cells. A cure for or treatment of any viral disease will require a lot more research into drug development, safety assessment and clinical trials in animal and then human populations. This process would be lengthy and may not necessarily prove successful.
• The researchers did not actually use the virus that causes the ‘common cold’ (rhinovirus) in this study, but rather one that can cause other respiratory illnesses (adenovirus) often with similar symptoms.
• Viruses can vary in their structure and properties. The findings would need to be replicated with other types of viruses to know whether the antibody response is the same. However, the researchers did observe the effect in a number of different cells types and antibodies.

This is promising research that may lead to a number of useful medical developments. However, it should be emphasised that these may be a long way off.

Links To The Headlines

A cure for the common cold may finally be achieved as a result of a remarkable discovery in a Cambridge laboratory. The Independent, November 2 2010

Cure for common cold on cards after medical breakthrough. The Daily Telegraph, November 2 2010

Cure for the common cold breakthrough raises hope. Daily Mail, November 2 2010

Immune discovery opens up new line of attack against viruses. The Guardian, November 2 2010

Cold comfort. Daily Mirror, November 2 2010

Links To Science

Mallery, DL, McEwan, WA, Bidgood, SR, et al. Antibodies Q:1 mediate intracellular; 2 immunity through tripartite motif-containing 21 (TRIM21). PNAS 2010


http://www.guardian.co.uk/science/2010/nov/01/viruses-immune-system-antibody

Three you don't want to catch

The common cold Caused by the human rhinovirus and named after the Greek for nose, it affects more people than any other virus. There are around 200 different viruses that cause the cold and it is this variability, combined with its ability to mutate, that makes the common cold so hard to cure. Adults can expect to catch two to four colds a year. Children, who have less-developed immune systems, typically get three to eight colds a year.

Gastroenteritis This is the leading cause of severe diarrhoea and dehydration in children in developed and developing countries and is caused by the rotavirus, which infects the stomach and bowel. The World Health Organisation estimates that the rotavirus is to blame for between 20% and 70% of hospital admissions due to diarrhoea.

Winter vomiting disease Caused by norovirus, or "small round structured virus", it is highly infectious and spreads quickly through hospitals, schools, nursing homes, and on cruise ships – where people are in closely-confined environments. The illness is generally mild but can take people two or three days to get over. Unlike rotavirus, people are susceptible to norovirus at any age, because immunity to the bug is short-lived.