Navigation Links
Ebola protein blocks early step in body's counterattack on virus
Date:8/13/2014

One of the human body's first responses to a viral infection is to make and release signaling proteins called interferons, which amplify the immune system response to viruses. Over time, many viruses have evolved to undermine interferon's immune-boosting signal, and a paper published today in the journal Cell Host & Microbe describes a mechanism unique to the Ebola virus that defeats attempts by interferon to block viral reproduction in infected cells.

The newly published study explains for the first time how the production by the virus of a protein called Ebola Viral Protein 24 (eVP24) stops the interferon-based signals from ramping up immune defenses. With the body's first response disabled, the virus is free to mass produce itself and trigger the too-large immune response that damages organs and often becomes deadly as part of Ebola virus disease (EVD).

The study was led by scientists from Washington University School of Medicine in St. Louis in collaboration with researchers from the Icahn School of Medicine at Mount Sinai and the University of Texas Southwestern Medical Center.

"Our study is the first to show how Ebola viral protein 24 defeats the signal sent by interferons, the key signaling molecules in the body's early response to Ebola virus infection," said Christopher F. Basler, PhD, Professor of Microbiology at the Icahn School of Medicine at Mount Sinai, and an author of the newly published paper. "These newfound details of Ebola biology are already serving as the foundation of a new drug development effort, albeit in its earliest stages," said Dr. Basler, also a researcher within the Mount Sinai Global Health and Emerging Pathogens Institute.

"We've known for a long time that infection with Ebola virus obstructs an important arm in our immune system that is activated by molecules called interferons," said senior author Gaya Amarasinghe, PhD, Assistant Professor of Pathology and Immunology at Washington University School of Medicine in St. Louis. "By determining the structure of an eVP24 in complex with a cellular transporter, we learned how Ebola does this."

Ebola Defeats Immune Defenses Early in Infection

The study spotlights the part of the body's defense system that fights infection called innate immunity, the mix of proteins and cells that most quickly recognizes an invasion by a virus. This part of immunity keeps a virus from quickly reproducing inside cells.

To trigger an effective, early response to viral infection, interferons must pass on their signal to other cells. This occurs through other messengers inside cells as part of interferon signaling pathways, with the last of these messengers turning on genes inside the nuclei of cells to drive the immune response.

The current study determined the structure of eVP24 when bound to its cellular targets, transport proteins called karyopherins. The study used these structures to show how, in place of interferon's natural downstream signal carrier phosphorylated STAT1, eVP24 docks into the karyopherins meant to escort STAT1 into cell nuclei where it turns on interferon-targeted genes. By elegantly interfering at this stage, eVP24 cripples innate immunity to cause EVD.

In 2006, Dr. Basler and colleagues found that the Ebola virus suppresses the human immune response through eVP24, but not how. Through of combination of molecular biology techniques, cell studies and tests that reveal protein structures, the current team led by Dr. Amarasighe defined the molecular basis for how eVP24 achieves this suppression.

Understanding exactly how the Ebola virus targets the interferon pathway could help guide drug development moving forward. Dr. Basler describes how it may be possible to find an antibody or molecule that interferes with eVP24, or that works around its competition with STAT1, such that treatment of patients with extra interferon, long used against the hepatitis C virus for instance, might become useful against the Ebola virus.

"We feel the urgency of the present situation, but still must do the careful research to ensure that any early drug candidates against the Ebola virus are proven to be safe, effective and ready for use in future outbreaks," said Dr. Basler, who is also principal Investigator of an NIH-funded Center of Excellence for Translational Research (CETR) focused on developing drugs to treat Ebola virus infections.


'/>"/>
Contact: Greg Williams
newsmedia@mssm.edu
212-241-9200
The Mount Sinai Hospital / Mount Sinai School of Medicine
Source:Eurekalert

Related biology news :

1. Sierra Leone samples: Ebola evidence in West Africa in 2006
2. Ebola vaccine success highlights dilemma of testing on captive chimps to save wild apes
3. Inserm and the Institut Pasteur identify a new variant of Ebola virus in Guinea
4. NIH grants up to $28 million to group led by Scripps Research for work on ebola treatment
5. UTMB collaborates on program targeting potential bioterrorist pathogens Ebola and Marburg
6. Recent study suggests bats are reservoir for ebola virus in Bangladesh
7. From eons to seconds, proteins exploit the same forces
8. Reduction of tau protein improves symptoms in model of severe childhood epilepsy
9. Protecting newborns: milk protein could save millions from harm
10. Discovery of new form of dystrophin protein could lead to therapy for some DMD patients
11. OncoPlex Diagnostics Announces the Addition of the Androgen Receptor Protein to Their Quantitative Breast Cancer Proteomic Panel
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:11/30/2016)... CHICAGO , Nov. 30, 2016  higi ... a new partnership initiative targeting national brands, industry ... and reward their respective audiences for taking steps ... Since its inception in 2012, higi has built ... US, impacting over 38 million people who have ...
(Date:11/29/2016)... France , November 29, 2016 Nearly one ... Continue Reading ... ... is part of an efficient Identity Management. (PRNewsFoto/DERMALOG Identification Systems) ... DERMALOG is Germany's largest Multi-Biometric supplier: ...
(Date:11/22/2016)... , November 22, 2016 According to the ... IRIS, Palm Print, Face, Vein, Signature, Voice), Multi-Factor), Component (Hardware and Software), ... published by MarketsandMarkets, the market is expected to grow from USD 10.74 ... CAGR of 16.79% between 2016 and 2022. ... ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... 2016  Soligenix, Inc. (OTCQB: SNGX) (Soligenix or ... developing and commercializing products to treat rare diseases ... today the long-term follow-up data from its Phase ... Innate Defense Regulator (IDR), in the treatment of ... patients undergoing chemoradiation therapy (CRT).  The additional 12-month ...
(Date:12/8/2016)... 8, 2016 Savannah River Remediation LLC ... selected NewTechBio,s NT-MAX Lake & Pond Sludge ... bacteria, in conjunction with Hexa Armor/ Rhombo cover ... National Pollutant Discharge Elimination System requirements. ... steady history of elevated pH levels, above 8.5, ...
(Date:12/8/2016)... , Dec. 8, 2016   Biocept, ... leading commercial provider of clinically actionable liquid biopsy ... announces that clinical data featuring its Target Selector™ ... tissue biopsy for the detection of actionable biomarkers ... from research sponsored by Sara Cannon Research Institute ...
(Date:12/7/2016)... ... December 07, 2016 , ... Huffman Engineering, Inc. ... a Wonderware Certified System Integrator Partner. Huffman Engineering is the only Nebraska-based ... “The System Integrator Partner certification gives customers confidence that our engineers are fully ...
Breaking Biology Technology: