Map of herpes virus protein suggests a new drug therapy
The mechanism by which a herpes virus invades cells has remained a mystery to scientists seeking to thwart this family of viruses. 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.
- A collaboration solves the herpes virus protein structure providing new drug therapy directionsMon, 26 Jul 2010, 13:30:45 EDT
- A drug against AIDS could be effective against the herpes virusThu, 23 Sep 2010, 10:45:14 EDT
- VAI study rules out transcriptional coactivators as useful herpes antiviral drug targetsWed, 25 Mar 2009, 17:58:47 EDT
- Researchers visualize herpes virus' tactical maneuverThu, 6 Jan 2011, 18:03:34 EST
- Antiviral therapy associated with fewer recurring eye problems from herpes simplex virusMon, 13 Sep 2010, 17:23:04 EDT
- Map of herpes virus protein suggests a new drug therapyfrom Science CentricWed, 7 Jul 2010, 9:42:12 EDT
- Map of herpes virus protein suggests a new drug therapyfrom Science DailyTue, 6 Jul 2010, 12:28:24 EDT
- Map of herpes virus protein suggests a new drug therapyfrom Science BlogTue, 6 Jul 2010, 11:21:19 EDT
- Map of herpes virus protein suggests a new drug therapyfrom PhysorgTue, 6 Jul 2010, 11:07:26 EDT
- Map of Herpes Virus Protein Suggests a New Drug Therapyfrom Newswise - ScinewsTue, 6 Jul 2010, 10:35:33 EDT
Latest Science NewsletterGet the latest and most popular science news articles of the week in your Inbox! It's free!
Learn more about
Check out our next project, Biology.Net
From other science news sites
Popular science news articles
- Even with defects, graphene is strongest material in the world
- Detection of the cosmic gamma ray horizon: Measures all the light in the universe since the Big Bang
- Genetic engineering alters mosquitoes' sense of smell
- Allosaurus fed more like a falcon than a crocodile, new study finds
- 'Popcorn' particle pathways promise better lithium-ion batteries