Researchers discover key mechanism by which lethal viruses Ebola and Marburg cause disease

Discovery is expected to lead to new drugs for treatment of certain viral hemorrhagic fevers in humans and apes

Researchers in the Greene Infectious Disease Laboratory at Columbia University's Mailman School of Public Health, the Centers for Disease Control and Prevention, and the Caribbean Primate Research Center have discovered a key mechanism by which the Filoviruses, Ebola and Marburg, cause disease. The identification of an amino acid sequence in Filoviruses that results in the rapid depression of immunological response is described in the December 2006 issue of The FASEB Journal. Using this information, researchers can begin to develop new drugs to stop these devastating diseases.

Filoviruses, named for their threadlike appearance in electron microscopy (filo= thread in Latin), are associated with outbreaks of fatal hemorrhagic fever in sub-Saharan Africa. Viral hemorrhagic fevers are of specific concern because they are associated with high morbidity and mortality (up to 80% mortality rates) and the potential for rapid dissemination through human-to-human transmission. The term "viral hemorrhagic fever" characterizes a severe multisystem syndrome associated with fever, shock, and bleeding caused by infection with one of a number of viruses, including the Filoviruses Ebola and Marburg.

Both humans and apes are susceptible to viral hemorrhagic fevers, and it is speculated that filovirus infections account at least in part for the recent decline in the gorilla and chimpanzee population in central Africa. There is no cure or approved vaccine for either Marburg or Ebola virus. Immunosuppression occurs early after infection and allows the viruses to reproduce rapidly and cause disease.

"Currently, there is no way to treat most viral hemorrhagic fever outbreaks, and increased international travel, trafficking in wildlife, political instability, and terrorism have made emerging infectious diseases a global concern," stated W. Ian Lipkin, MD, director of the Greene Infectious Disease Laboratory at the Mailman School's Department of Epidemiology and professor of Epidemiology, Neurology, and Pathology at Columbia University. "The identification of this new mechanism for immunosuppression is anticipated to lead to new drugs for intervention in filoviral hemorrhagic fevers of humans and apes."

In the study, researchers describe a series of amino acids in Ebola and Marburg viruses that resemble proteins in retroviruses known to suppress the immune system. By targeting these amino acids, new drugs could disrupt the ability of these viruses to shut down immune systems and make them vulnerable to the body's natural defenses.

"This brilliant study shows that many viruses, including HIV, use a similar mechanism to disarm their victims," said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. "The Columbia study has shown us new ways to fight against deadly viruses the world over."

The method for discovering this protein underscores the power of bioinformatics for addressing the challenges of emerging infectious diseases. The investigators are currently exploring whether insights derived from understanding the potency of these immunosuppressive peptides can be exploited to treat autoimmune diseases.

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About the Mailman School of Public Health

The only accredited school of public health in New York City, and among the first in the nation Columbia University's Mailman School of Public Health provides instruction and research opportunities to more than 950 graduate students in pursuit of masters and doctoral degrees. Its students and more than 270 multi-disciplinary faculty engage in research and service in the city, nation, and around the world, concentrating on biostatistics, environmental health sciences, epidemiology, health policy and management, population and family health, and sociomedical sciences.

About the Jerome L. and Dawn Greene Infectious Disease Laboratory

The Jerome L. and Dawn Greene Infectious Disease Laboratory is located at the Mailman School of Public Health. In addition to establishing methods for diagnosis, prevention, and treatment of acute outbreaks of infectious disease, Laboratory scientists investigate links between infection and a wide range of chronic diseases including autism, attention deficit hyperactivity disorder, obsessive compulsive disorders, depression, schizophrenia, diabetes mellitus, and cancer that have their origins in early or even prenatal life.

About The FASEB Journal

The FASEB Journal (www.fasebj.org) is published by the Federation of American Societies for Experimental Biology (FASEB) and is consistently ranked among the top three biology journals worldwide by the Institute for Scientific Information. FASEB comprises 21 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB's mission is to enhance the ability of biomedical and life scientists to improve through their research the health, well-being and productivity of all people. FASEB serves the interests of these scientists in those areas related to public policy, facilitates coalition activities among member societies and disseminates information on biological research through scientific conferences and publications.


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