New research funded by the National Institutes of Health and published online in advance of print in Nature Structural & Molecular Biology reveals the unusual structure of the protein complex that allows a herpes virus to invade cells. This detailed map of a key piece of the herpes virus “cell-entry machinery” gives scientists a new target for antiviral drugs.
“Most viruses need cell-entry proteins called fusogens in order to invade cells. We have known that the herpes virus fusogen does not act alone and that a complex of two other viral cell-entry proteins is always required. We expected that this complex was also a fusogen, but after determining the structure of this key protein complex, we found that it does not resemble other known fusogens,” said senior author Ekaterina Heldwein, PhD, assistant professor in the molecular biology and microbiology department at Tufts University School of Medicine.
“This unexpected result leads us to believe that this protein complex is not a fusogen itself but that it regulates the fusogen. 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,” Heldwein continued. Heldwein is also a member of the biochemistry and molecular microbiology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.
“Katya Heldwein’s work has resulted in a map of the protein complex needed to trigger herpes virus infection. The NIH Director's New Innovator Awards are designed to support such breakthroughs. This research not only adds to what we know about how herpes viruses infect mammalian cells, but also sets the stage for new therapeutics that restrict herpes virus’s access to the cell,” said Jeremy M. Berg, PhD, director of the National Institute of General Medical Sciences (NIGMS) at the National Institutes of Health.
“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. Knowing the structures of cell-entry proteins will help us find the best strategy for interfering with this pervasive family of viruses,” said first author Tirumala K. Chowdary, PhD, a postdoctoral associate in the department of molecular biology and microbiology at TUSM and member of Heldwein’s lab.
Currently, 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), which causes cold sores, by the time they reach their 20s. Currently, about one in six Americans is infected with herpes simplex virus type 2 (HSV-2), 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 newborn infants.
Heldwein teamed up with colleagues at University of Pennsylvania and used x-ray crystallography along with cell microscopy techniques to study the structure and function of this cell-entry protein complex in HSV-2. Heldwein is currently developing a molecular movie that illustrates how herpes virus enters the cell.
Additional authors are Tina Cairns, PhD, a research specialist; Doina Atanasiu, a research associate; and Gary Cohen, PhD, professor and chair, all in the department of microbiology at the University of Pennsylvania School of Dental Medicine; and Roselyn Eisenberg, PhD, professor in the department of microbiology at the University of Pennsylvania School of Veterinary Medicine.
This work was funded by the Office of the Director of the National Institutes of Health, through a New Innovator Award in 2007 to Ekaterina Heldwein. The New Innovator Awards, part of the NIH Roadmap for Medical Research initiative, are awarded to support early-career scientists who take innovative – and potentially transformative – approaches to major challenges in biomedical research. The work was also funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Pew Scholar Program in Biomedical Sciences.
Chowdary TK, Cairns TM, Atanasiu D, Cohen GH, Eisenberg RJ, Heldwein EE. Nature Structural & Molecular Biology. 2010. “Crystal structure of the conserved herpesvirus fusion regulator complex gH-gL.” Published online July 4, 2010, doi: 10.1038/nsmb.1837About Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences
Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.
Siobhan Gallagher | Newswise Science News
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
17.08.2018 | Event News
08.08.2018 | Event News
27.07.2018 | Event News
17.08.2018 | Physics and Astronomy
17.08.2018 | Information Technology
17.08.2018 | Life Sciences