From: Subject: Single host gene may hold key to treating both ebola and anthrax infections Date: Sat, 22 Aug 2009 10:37:34 -0700 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_000E_01CA2314.8FA39160" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_000E_01CA2314.8FA39160 Content-Type: text/html; charset="iso-8859-1" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.eurekalert.org/pub_releases/2009-08/uamr-shg082009.php Single host gene may hold key to treating both ebola = and anthrax infections

=20 Public release date: 20-Aug-2009
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Contact: Caree Vander Linden
Caree.Vanderlinden@us.army= .mil
301-619-2285
US Army = Medical Research=20 Institute of Infectious Diseases

Single host gene may hold key to treating both ebola = and anthrax=20 infections

Research published by Army scientists indicates that a minor = reduction in=20 levels of one particular gene, known as CD45, can provide protection = against two=20 divergent microbes: the virus that causes Ebola hemorrhagic fever and = the=20 bacterium that causes anthrax. Taken together, the results suggest a = common host=20 restriction factor and a promising approach to drug development for = treating two=20 completely different infections.

Writing in the August 20 online issue of Cell Host and = Microbe,=20 scientists at the U.S. Army Medical Research Institute of Infectious = Diseases=20 (USAMRIID) reported that mice expressing reduced levels of CD45 (between = 11 and=20 77 percent) were protected against Ebola virus. In addition to an = overall=20 survival rate of 90 to 100 percent, these mice had reduced levels of = virus load=20 in the major organs, and had completely cleared the virus 10 days after=20 challenge.

In contrast, mice that had naturally occurring levels of CD45=97or = none at all=97=20 failed to clear the virus and succumbed to infection within 7 to 8 days=20 following challenge.

The protein encoded by CD45 is a member of the protein tyrosine = phosphatase=20 (PTP) family. PTPs are known to be signaling molecules that regulate a = variety=20 of cellular processes, including cell growth, cell division, and the = development=20 of malignancies that can lead to tumor formation.

Scientists created various "knockdown" mice, which expressed reduced = levels=20 of CD45, to determine how those changes may alter the body's immune = response to=20 microbial pathogens such as Ebola virus. According to the authors, the=20 "knockdown" mice retained greater control of gene expression and immune = cell=20 proliferation following Ebola virus infection. These factors contributed = to=20 enhanced viral clearance, increased protection against the virus, and a=20 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 immune system, = which can=20 be determined by the levels of a single regulator gene.

Ebola virus, which causes hemorrhagic fever with human case fatality = rates up=20 to 80 percent, is a global health concern and a potential biological = threat.=20 Currently there are no available vaccines or therapies. Scientists at = USAMRIID=20 study the Ebola virus to support development of medical products to = prevent and=20 treat infection.

The recently published work builds upon a related study that appeared = in the=20 Journal of Biological Chemistry in May of this year. That research = showed that=20 CD45 also plays a role in protection from Bacillus anthracis, the = causative=20 agent of anthrax. Specifically, the USAMRIID team demonstrated that in = mice=20 expressing 62 percent of the CD45 gene, about 70 percent were protected=20 following exposure to anthrax.

Bacillus anthracis causes three types of disease=97cutaneous, = gastrointestinal,=20 and inhalational=97depending upon the route of exposure. A licensed = vaccine is=20 available, and is protective if administered before exposure. = Inhalational=20 anthrax is difficult to diagnose early, and despite antibiotic therapy, = has a=20 high fatality rate. In addition, because anthrax spores can remain in = the body=20 for extended periods, antibiotic treatment is typically recommended for = 60 days=20 or more following exposure.

"This report demonstrates the critical connection between basic = research and=20 the potential development of medical products," said COL John P. = Skvorak,=20 commander of USAMRIID. "Understanding pathogenesis of disease and host = response=20 is critical to the Department of Defense's investment in broad spectrum=20 countermeasures."

The next step for investigators is to look at the mechanism of action = to=20 better understand how reduced expression of this gene regulates the = pathogenesis=20 of both diseases. That information could one day lead to the = identification and=20 discovery of additional promising compounds for treating Ebola and = anthrax=20 infections.

###

Both studies were supported by grants from the Defense Threat = Reduction=20 Agency, the National Institutes of Health, the National Cancer = Institute, and=20 the National Institute of Allergy and Infectious Diseases.

USAMRIID, located at Fort Detrick, Maryland, is the lead medical = research=20 laboratory for the U.S. Biological Defense Research Program, and plays a = key=20 role in national defense and in infectious disease research. The = Institute=20 conducts basic and applied research on biological threats resulting in = medical=20 solutions (such as vaccines, drugs and diagnostics) to protect the = warfighter.=20 While USAMRIID's primary mission is focused on the military, its = research often=20 has applications that benefit society as a whole. USAMRIID is a = subordinate=20 laboratory of the U.S. Army Medical Research and Materiel Command. For = more=20 information, visit www.usamriid.army.mil.

References:

Rekha G. Panchal, Steven B. Bradfute, Brian D. Peyser, Kelly L. = Warfield,=20 Gordon Ruthel, Douglas Lane, Tara A. Kenny, Arthur O. Anderson, William = C.=20 Raschke and Sina Bavari. "Reduced Levels of Protein Tyrosine Phosphatase = CD45=20 Protect Mice from the Lethal Effects of Ebola Virus Infection," Cell = Host and=20 Microbe (August 2009).

Rekha G. Panchal, Ricky L. Ulrich, Steven B. Bradfute, Douglas Lane, = Gordon=20 Ruthel, Tara A. Kenny, Patrick L. Iversen, Arthur O. Anderson, Rick = Gussio,=20 William C. Raschke, and Sina Bavari. "Reduced Expression of CD45=20 Protein-tyrosine Phosphatase Provides Protection against Anthrax = Pathogenesis,"=20 Journal of Biological Chemistry (May 2009).

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