Research published by Army scientists indicates that a minor reduction in levels of one particular gene, known as CD45, can provide protection against two divergent microbes: the virus that causes Ebola hemorrhagic fever and the bacterium that causes anthrax. Taken together, the results suggest a common host restriction factor and a promising approach to drug development for treating two completely different infections.
Writing in the August 20 online issue of Cell Host and Microbe, scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) reported that mice expressing reduced levels of CD45 (between 11 and 77 percent) were protected against Ebola virus. In addition to an overall survival rate of 90 to 100 percent, these mice had reduced levels of virus load in the major organs, and had completely cleared the virus 10 days after challenge.
In contrast, mice that had naturally occurring levels of CD45or none at all failed to clear the virus and succumbed to infection within 7 to 8 days following challenge.
The protein encoded by CD45 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, cell division, and the development of malignancies that can lead to tumor formation.
Scientists created various "knockdown" mice, which expressed reduced levels of CD45, to determine how those changes may alter the body's immune response to microbial pathogens such as Ebola virus. According to the authors, the "knockdown" mice retained greater control of gene expression and immune cell proliferation following Ebola virus infection. These factors contributed to enhanced viral clearance, increased protection against the virus, and a reduction in cell death.
The team's results suggest that host susceptibility to Ebola virus is dependent on the delicate balance of the body's natural i
|Contact: Caree Vander Linden|
US Army Medical Research Institute of Infectious Diseases