A research team led by UCR Associate Professor of Biomedical Sciences Dr. Ilhem Messaoudi recently made a breakthrough in the management and detection of yellow fever, a tropical disease responsible for 200,000 infections and 30,000 deaths annually.
According to Dr. Messaoudi, the goal of the project was to gain a better understanding of the mechanisms by which the yellow fever virus can lead to death, which, she says are not currently well understood. The project was accomplished through the collaboration of Staff Research Associate Flora Engelmann and Associate Professor of Bioinformatics Thomas Girke of UC Riverside, along with several researchers from various other institutions.
Although the three-year project was completed at the end of 2013, the team spent several months organizing data and writing a manuscript, which were only reviewed and accepted by Public Library of Science, a literary science journal, on Nov. 20.
Yellow fever, an acute viral disease primarily transmitted by mosquitos, can also be transmitted between monkeys and humans. According to the World Health Organization, the number of yellow fever infections has increased over the past two decades, and all existing treatments can only alleviate the symptoms of yellow fever, such as fever and vomiting, but not their causes.
Lack of proper treatment has played a part in the virus’ often lethal nature, a problem which was addressed by the study, the results of which will “provide future targets for antiviral therapeutics and better diagnostics,” according to the author summary of the paper.
According to Messaoudi, the project, conducted on infected monkeys at Oregon Primate National Research Center, led to three major findings. Prior to the study, it was known that the virus targets the liver and causes severe organ damage, but the symptoms present during the first 48 hours are not specific to the disease, leading to delayed diagnoses.
The study showed that fatal yellow fever infection typically causes severe lymphopenia, the loss of white cells that defend against infections. According to Messaoudi, the presence of lymphopenia can serve as a “disease progression marker” for yellow fever, since it appears before certain changes in the liver. The findings provide researchers with an earlier window for detection, which would allow for more aggressive treatment against yellow fever.
The second finding, which Messaoudi describes as “the biggest surprise” of the study, was the number of differentially expressed genes very early on in infection, even before the onset of symptoms. Messaoudi explained that “the genes associated with the first line of defense (against disease), the innate immune system, were down regulated,” referring to the process by which a cell decreases the quantity of a certain cellular component in response to an external influence. This helps explain the immune system’s difficulty fighting the disease. It was also found that genes associated with inflammation were up regulated, helping to explain the organ damage the disease often causes. This leads to the study’s third major finding, which is that the virus only replicates in the liver, which suggests that the damage often seen in other organs is a result of the increase of inflammatory cytokines — proteins secreted by immune system cells — that come from the virus aggressively replicating in the liver.
Messaoudi feels that yellow fever is largely a “neglected tropical disease” and that its study can lead to “more insight into more deadly diseases such as ebola and hemorrhagic fever,” demonstrating the study’s relevance on a global scale.
Messaoudi and her colleagues hope to conduct future studies to further improve our understanding of the process by which the yellow fever virus causes disease and death.