Date Published: 28 August 2005
Researcher investigates what happens when a virus enters the body
It is widely accepted that viruses are involved in many diseases such as the 'common cold' to herpes, and AIDS. Some types of cancer have been also linked to viruses.
Leading immunologist and presenter Dr Polly Matzinger, currently leader of a laboratory of the National Institutes of Health (NIH) USA, has recently caused some controversy among experts in the understanding of the autoimmune system. Her "danger model," considers the possibility that the immune system is more concerned with damage detected on the death of biological cells than with the introduction of foreign invaders, such as viruses. If this is correct, then decades of scientific and medical diagnostic thinking may be reviewed.
A new NIH grant has recently been awarded to Amy Bell, an electrical and computer engineer (ECE), and Karen Duca, a research assistant professor at the Virginia Bioinformatics Institute (VBI), both of Virginia Tech. This will fund research that might lead to answers to some questions about the human body's responses to viruses.
Before Matzinger's "danger model", the general scientific concensus was that the body's cells recognize substances, such as 'germs' that do not come from within that body itself. It was generally accepted that such recognition triggered the immune system's attempt to render the invader harmless and remove it from the body. However, according to Matzinger, the body discriminates between things that are dangerous and things that are not. It does this by defining anything that does damage as dangerous. Through this selectivity process, the immune system does not respond to things that don't damage it. It is an idea that makes intuitive sense and is supported by various examples from nature - such as the body recognizes invading substances that are not dangerous, such as the development of a fetus during a woman's pregnancy and the production of milk by lactating women.
The question is: Do we really know what a body's host cell does when a virus infects it ?
Bell and Duca's collaboration is an attempt to profile the host-virus system using the electrical engineering concepts of signal and image processing. As Duca, a biophysicist, introduces viruses into cells in a laboratory dish, she infects only the cell's center. Then, she and Bell, who is also currently associated with VBI as one of its faculty fellows, study the response as the virus moves outward. Their method differs from conventional laboratory studies of viruses that generally involve infecting the entire dish at once. As the virus moves out from the center in its attempt to infect other healthy cells, Duca identifies and stains relevant markers from the virus and the host. Under ultraviolet lighting, the chemical stains become fluorescent, allowing Bell and Duca to capture images of the laboratory dish at regular time intervals as the infection progresses. The images then provide Bell and Duca with information about innate immune responses to viruses.
Using the NIH support of almost $400,000, Bell plans to next remove the noise from these low-resolution images, creating what she calls a clean immuno-fluorescent intensity signal. The noise she refers to is not audible to the human ear. From an electrical engineering standpoint, noise in this example includes the spurious artifacts that appear in the image due to the microscope's uneven source illumination. Noise can also result from the spectral overlap of the fluorescent markers that Duca uses.
Also, since the microscope cannot capture the entire laboratory dish at once, multiple sub-images must be taken quickly, then reassembled in the proper matrix. The "montage" artifact arises from the microscope's uneven illumination, which is brighter in the center and dissipates nearer the edges of the dish for each sub-image.
To compensate for this artifact or noise, Bell's lab has developed a method to remove the grid created by assembling the montage of sub-images.
" Our method ? based on a model we developed that reflects the physics of fluorescent microscopy ? also estimates and corrects the effect of the microscope's uneven illumination and the markers' spectral overlap," explained Bell.
As Bell and Duca are able to develop their composite images, they will be able to mathematically produce a quantitative description of the spreading of the virus as well as the host-virus interaction.
"The immuno-fluorescent intensity signals (IIS) depict how the virus and host are interacting over time, from the point of origin to the point of infection," said Bell.
This interdisciplinary team hope that their efforts will lead to a quantitative method that derives a characteristic profile or fingerprint from the IIS of any host-virus system. If their method can achieve results in hours instead of days, this technique could be used in clinical and field settings to quickly identify known viruses, or to map unknown viruses to existing profiles to better predict their behavior and start appropriate treatment.
Source: Virginia Polytechnic Institute and State University (USA).