|How the white-footed mouse can help humans fight diseases|
Clues sought for treatment of flaviviruses by studying cells
By ADAEZE IZUOGU | SPECIAL TO THE BLADE
Published on June 6, 2016
Adaeze Izuogu is a PhD student in the department of medical microbiology and immunology at the University of Toledo college of medicine.
Have you ever wondered if animals get sick with the same infections that affect humans?
In recent years, the world has been threatened with dangerous disease-causing viruses such as Ebola, Dengue, SARS, and currently, Zika virus. These viruses all infect animals before transmission to humans. Curiously, most infected animals do not get sick despite infection. It is a puzzle to researchers that these animals resist the viral diseases and suggests that the animals have some survival secrets that we humans do not.
A group of viruses called flaviviruses presents an even more complex picture of human virus infection and disease. These include many widespread viruses such as West Nile, Zika, Powassan, and tick-borne encephalitis virus. An insect vector is required to transmit these viruses from animals to humans, which most often occurs by the bite of a mosquito or tick that had previously bitten an infected animal.
The human disease that develops from the infected insect could involve a simple fever or a very severe multi-organ illness or even brain damage with possible long-term consequences. Unfortunately, there is currently no specific treatment for infection with this group of viruses, and up to 60 percent of people who develop disease can die from infection.
Our studies, conducted in the laboratory of Dr. Travis Taylor at the University of Toledo College of Medicine and Life Sciences, are seeking clues for treatment of flaviviruses by studying cells of a natural animal host: the white-footed mouse (Peromyscus leucopus). This is the most common wild rodent in North America.
Ticks infected with flavivirus that bite a white-footed mouse can pass the flavivirus to that mouse. The mouse remains infected for a long time but without disease symptoms. Any other tick that then bites this mouse for a blood meal can acquire the flavivirus infection and transmit it to a human.
The main goal of our research is to identify how the white-footed mouse remains free of disease while infected with the flavivirus, unlike humans. If we can find the exact process of defense against disease in the white-footed mouse, we may be able to use a similar approach to combat flavivirus disease in humans.
We discovered that the flavivirus grows to much lower numbers in cells in culture from the white-footed mouse as compared to cells from the house mouse (Mus musculus), which is not resistant to flavivirus disease symptoms.
We have now tested several strains of tick-borne flaviviruses. Every strain tested exhibits the same low numbers in cells of the white-footed mouse. Further research revealed that flavivirus growth in the white-footed mouse is blocked when the virus attempts to make more copies of itself within the cell, which is why there are fewer virus particles in the cell culture as compared to the house mouse.
So why is the same flavivirus more dangerous in some species than others? We believe this difference is because the white-footed mouse’s higher immune system activity defends against virus particles. Generally, the higher the activity of your immune system, the better your defense against disease will be.
The next step was to identify the main biochemical pathway involved in defense. We used molecular tools to block the interferon response, which is the body’s process of sensing viral infection and activating an immune defense. We discovered that when this pathway is blocked in cells of the white-footed mouse, there are many more virus particles in these cells. This suggests that the white-footed mouse cell defense activity suppresses virus growth.
We’ve learned that virus detection and interferon activation prevent the growth of flaviviruses in the white-footed mouse. The next step is to identify specific proteins in this mouse that are triggered by the interferon pathway to inhibit flavivirus disease after infection. We anticipate that these specific proteins will help in drug design by mimicking the survival strategy of the white-footed mouse.
Adaeze Izuogu is a PhD student in the Department of Medical Microbiology and Immunology in the University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Adaeze is doing her research in the laboratory of Dr. Travis Taylor. For more information, contactAdaeze.Izuogu@rockets.utoledo.edu
RELATED ITEMS: ADAEZE IZUOGU , UNIVERSITY OF TOLEDO , ZIKA VIRUS , DENGUE , SARS , EBOLA , WEST NILE VIRUS , DR. TRAVIS TAYLOR , FORMER MEDICAL COLLEGE OF OHIO