(Press-News.org) The pain and itching associated with shingles and herpes may be due to the virus causing a "short circuit" in the nerve cells that reach the skin, Princeton researchers have found.
This short circuit appears to cause repetitive, synchronized firing of nerve cells, the researchers reported in the journal Proceedings of the National Academy of Sciences. This cyclical firing may be the cause of the persistent itching and pain that are symptoms of oral and genital herpes as well as shingles and chicken pox, according to the researchers.
These diseases are all caused by viruses of the herpes family. Understanding how these viruses cause discomfort could lead to better strategies for treating symptoms.
The team studied what happens when a herpes virus infects neurons. For research purposes the investigators used a member of the herpes family called pseudorabies virus. Previous research indicated that these viruses can drill tiny holes in neurons, which pass messages in the form of electrical signals along long conduits known as axons.
The researchers' findings indicate that electrical current can leak through these holes, or fusion pores, and spread to nearby neurons that were similarly damaged, causing the neurons to fire all at once rather than as needed. The pores were likely created for the purpose of infecting new cells, the researchers said.
The investigators observed the cyclical firing of neurons in a region called the submandibular ganglia between the salivary glands and the brain in mice using a technique called 2-photon microscopy and dyes that flash brightly when neurons fire.
The team found that two viral proteins appear to work together to cause the simultaneous firing, according to Andréa Granstedt, who received her Ph.D. in molecular biology at Princeton in 2013 and is the first author on the article. The team was led by Lynn Enquist, Princeton's Henry L. Hillman Professor in Molecular Biology and a member of the Princeton Neuroscience Institute.
The first of these two proteins is called glycoprotein B, a fusion protein that drills the holes in the axon wall. A second protein, called Us9, acts as a shuttle that sends glycoprotein B into axons, according to the researchers. "The localization of glycoprotein B is crucial," Granstedt said. "If glycoprotein B is present but not in the axons, the synchronized flashing won't happen."
The researchers succeeded in stopping the short circuit from occurring in engineered viruses that lacked the gene for either glycoprotein B or Us9. Such genetically altered viruses are important as research tools, Enquist said.
Finding a way to block the activity of the proteins could be a useful strategy for treating the pain and itching associated with herpes viral diseases, Enquist said. "If you could block fusion pore formation, you could stop the generation of the signal that is causing pain and discomfort," he said.
Granstedt conducted the experiments with Jens-Bernhard Bosse, a postdoctoral research associate in molecular biology. Assistance with 2-photon microscopy was provided by Stephan Thiberge, director of the Bezos Center for Neural Circuit Dynamics at the Princeton Neuroscience Institute.
The team previously observed the synchronized firing in laboratory-grown neurons (PLoS Pathogens, 2009), but the new study expands on the previous work by observing the process in live mice and including the contribution of Us9, Granstedt said.
Shingles, which is caused by the virus herpes zoster and results in a painful rash, will afflict almost one out of three people in the United States over their lifetime. Genital herpes, which is caused by herpes simplex virus-2, affects about one out of six people ages 14 to 49 years in the United States, according the Centers for Disease Control and Prevention.
INFORMATION:
This research was funded by National Institutes of Health (NIH) Grants NS033506 and NS060699. The Imaging Core Facility at the Lewis-Sigler Institute is funded by NIH National Institute of General Medical Sciences Center Grant PM50 GM071508.
Granstedt, Andréa E., Jens B. Bosse, Stephan Y. Thiberge, and Lynn W. Enquist. 2013. In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins. PNAS 2013 ; published ahead of print August 26, 2013, doi:10.1073/pnas.1311062110
END
Treatment with two common drugs reduced viral replication and lung damage when given to monkeys infected with the virus that causes Middle East Respiratory Syndrome. The condition is deadly pneumonia that has killed more than 100 people, primarily in the Middle East.
Middle East Respiratory Syndrome, or MERS, was first reported in Saudi Arabia last year. The infection is caused by a coronavirus, called MERS-CoV, which is closely related to several coronaviruses that infect bats. About half of patients who developed the syndrome have died. Currently, there is no proven ...
Paying doctors for how they perform specific medical procedures and examinations yields better health outcomes than the traditional “fee for service” model, where everyone gets paid a set amount regardless of quality or patient outcomes, according to new research conducted by UC San Francisco and the New York City Department of Health and Mental Hygiene.
“‘Pay for performance’ programs shift the focus from basic care delivery to high quality care delivery,” said first author Naomi Bardach, MD, assistant professor in the UCSF Department of Pediatrics. “So they are ...
Move over, plaques and tangles.
Researchers at Emory University School of Medicine's Alzheimer's Disease Research Center have identified a previously unrecognized type of pathology in the brains of patients with Alzheimer's disease.
These tangle-like structures appear at early stages of Alzheimer's and are not found in other neurodegenerative diseases such as Parkinson's disease.
What makes these tangles distinct is that they sequester proteins involved in RNA splicing, the process by which instructional messages from genes are cut and pasted together. The researchers ...
The search for the cause of multiple sclerosis, a debilitating disease that affects up to a half million people in the United States, has confounded researchers and medical professionals for generations. But Steven Schutzer, a physician and scientist at Rutgers New Jersey Medical School, has now found an important clue why progress has been slow – it appears that most research on the origins of MS has focused on the wrong part of the brain.
Look more to the gray matter, the new findings published in the journal PLOS ONE suggest, and less to the white. That change of approach ...
COLUMBUS, Ohio – After a period of relative calm during the 1990s, rapid changes in American families began anew during the 2000s, a new analysis suggests.
Young people delayed marriage longer than ever before, permanent singlehood increased, and divorce and remarriage continued to rise during the first decade of the century.
(See the top 5 trends in American families during the 2000s:
http://researchnews.osu.edu/archive/5Trends.htm)
But the most troubling finding, researchers say, may be how American families have taken divergent paths: White people, the educated ...
Researchers have discovered the first inherited gene mutation linked exclusively to acute lymphoblastic leukemia (ALL) occurring in multiple relatives in individual families. The discovery of the PAX5 gene mutation was led by St. Jude Children's Research Hospital and others. The work appears in the current advance online edition of the scientific journal Nature Genetics.
The mutation was identified in two unrelated families in which pediatric ALL has been diagnosed in multiple generations. The mutation involved a single change in the DNA sequence of PAX5, a gene that ...
Dingoes have been unjustly blamed for the extinctions on the Australian mainland of the Tasmanian tiger (or thylacine) and the Tasmanian devil, a University of Adelaide study has found.
In a paper published in the journal Ecology, the researchers say that despite popular belief that the Australian dingo was to blame for the demise of thylacines and devils on the mainland about 3000 years ago, in fact Aboriginal populations and a shift in climate were more likely responsible.
"Perhaps because the public perception of dingoes as 'sheep-killers' is so firmly entrenched, ...
PORTLAND, Ore. — During a three-year period in seven metropolitan areas in the western United States, the emergency medical services system sent more than 85,000 injured patients to major trauma hospitals who didn't need to go there — costing the health care system more than $130 million per year, according to an Oregon Health & Science University study published today in the journal Health Affairs.
The study gathered data from emergency services calls from 94 EMS agencies in the seven metropolitan areas from January 2006 through December 2008. The agencies were using ...
Contact: Michael Bernstein
m_bernstein@acs.org
317-262-5907 (Indianapolis Press Center, Sept. 6-11)
202-872-6042
Michael Woods
m_woods@acs.org
317-262-5907 (Indianapolis Press Center, Sept. 6-11)
202-872-6293
American Chemical Society
American Chemical Society issues guidelines for safer research laboratories
INDIANAPOLIS, Sept. 10, 2013 — The world's largest scientific society today issued guidelines to better ensure the safety of the tens of thousands of personnel who work in research laboratories around the country. The American Chemical Society ...
Contact: Michael Bernstein
m_bernstein@acs.org
317-262-5907 (Indianapolis Press Center, Sept. 6-11)
202-872-6042
Michael Woods
m_woods@acs.org
317-262-5907 (Indianapolis Press Center, Sept. 6-11)
202-872-6293
American Chemical Society
The real reason to worry about bees
INDIANAPOLIS, Sept. 10, 2013 — Honeybees should be on everyone's worry list, and not because of the risk of a nasty sting, an expert on the health of those beneficial insects said here today at the 246th National Meeting & Exposition of the American Chemical Society (ACS), the world's ...
