Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Collaboration Solves Structure of Herpes Virus Protein, Provides New Drug Directions

The mechanism by which a herpes virus invades cells has remained a mystery to scientists, but now research from Tufts University and the University of Pennsylvania reveals the unusual structure of a key member of the protein complex that allows a herpes virus to invade cells.

The new map details an essential piece of the herpes virus “cell-entry machinery,” providing scientists with a new target for antiviral drugs.

The research was published online in the journal Nature Structural & Molecular Biology.

Researchers at Tufts and Penn used X-ray crystallography along with cell microscopy techniques to study the structure and function of the cell-entry protein fusion events carried out by HSV-2. The research has resulted in a map of an important protein complex required to trigger herpes virus infection, setting the stage for new therapeutics that may prevent the virus's access to cells.

Most viruses need cell-entry proteins called fusogens in order to invade cells. Scientists have known that the herpes virus fusogen does not act alone, requiring a complex of two other viral cell-entry proteins. In this study, researchers determined the structure of this key protein complex and realized it did not resemble the structure of other known fusogens.

“This unexpected result leads us to believe that this protein complex is not a fusogen itself but that it regulates the fusogen,” said senior author Ekaterina Heldwein, assistant professor of molecular and microbiology at Tufts University School of Medicine. “We also found that certain antibodies interfere with the ability of this protein complex to bind to the fusogen, evidence that antiviral drugs that target this interaction could prevent viral infection.”

“We hope that determining the structure of this essential piece of the herpes virus cell-entry machinery will help us answer some of the many questions about how herpes virus initiates infection,” said first author Tirumala K. Chowdary, a postdoctoral associate at Tufts. “Knowing the structures of cell-entry proteins will help us find the best strategy for interfering with this pervasive family of viruses.”

There is no cure for herpes viruses. Upon infection, the viruses remain in the body for life and can stay inactive for long periods of time. When active, however, different herpes viruses can cause cold sores, blindness, encephalitis or cancers. More than half of Americans are infected with herpes simplex virus type 1, HSV-1, by the time they reach their 20s. About one in six Americans is infected with herpes simplex virus type 2, HSV-2, which is the virus responsible for genital herpes. Complications of HSV-2, a sexually-transmitted disease, include recurrent painful genital sores, psychological distress and, if transmitted from mother to child, potentially fatal infections in newborns.

Herpes viruses, which cause many incurable diseases, infect cells by fusing viral and cellular membranes. Whereas most other enveloped viruses use a single viral catalyst called a fusogen, herpes viruses inexplicably require two conserved fusion-machinery components, gB and the heterodimer gH-gL, plus other nonconserved components. gB is a class III viral fusogen, but, unlike other members of its class, it does not function alone.

“We determined the crystal structure of the gH ectodomain bound to gL from herpes simplex virus 2,” said Roselyn J. Eisenberg, professor of microbiology at the University of Pennsylvania School of Veterinary Medicine. “gH-gL is an unusually tight complex with a unique architecture that, unexpectedly, does not resemble any known viral fusogen.”

“We propose that gH-gL activates gB for fusion, possibly through direct binding,” said Gary Cohen, professor of microbiology at the University of Pennsylvania School of Dental Medicine. “Formation of a gB-gH-gL complex is critical for fusion and is inhibited by a neutralizing antibody, making the gB-gH-gL interface a promising antiviral target.”

The study was conducted by Heldwein and Chowdary of Tufts School of Medicine; Cohen, Tina Cairns and Doina Atanasiu of the Department of Microbiology at Penn Dental Medicine; and Eisenberg at Penn Vet.

Research was funded by the National Institutes of Health, the National Institute of Allergy and Infectious Diseases and the Pew Scholar Program in Biomedical Sciences.

Jordan Reese | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>