ScienceDaily
Your source for the latest research news
Follow Facebook Twitter LinkedIn Subscribe RSS Feeds Newsletters
New:
  • Black Death Shaped Evolution of Immunity Genes
  • Methane-Eating 'Borgs' Taking Earth's Microbes
  • Pain Relief Without Side Effects and Addiction
  • Accounting For Dark Energy and Dark Matter
  • Meet the First Neanderthal Family
  • Physicists Confirm Hitch in Proton Structure
  • Five Hours' Sleep a Night: Disease Risk
  • Energetics of Piercing Fangs and Claws
  • Hair Straightening Chemicals and Uterine Cancer
  • Ostriches With Similar Interests Form Groups
advertisement
Follow all of ScienceDaily's latest research news and top science headlines!
Science News
from research organizations

1

2

How dormant infections caused by childhood chicken pox can -- decades later -- trigger shingles

Date:
June 4, 2015
Source:
Bar-Ilan University
Summary:
Scientists report on a novel experimental model that, for the first time, successfully mimics the 'sleeping' and 'waking' of the varicella-zoster virus. Based on neurons generated from human embryonic stem cells, and not requiring the use of experimental animals, the model allows scientists to test drugs and develop therapies to prevent shingles. It may also contribute to the fight against other viruses -- such as herpes and polio -- that target the human nervous system.
Share:
FULL STORY

The red, itchy rash caused by varicella-zoster -- the virus that causes chickenpox -- usually disappears within a week or two. But once infection occurs, the varicella-zoster virus, or VZV, remains dormant in the nervous system, awaiting a signal that causes this "sleeper" virus to be re-activated in the form of an extremely unpleasant but common disease: herpes zoster, or shingles.

advertisement

In a study recently published in PLOS Pathogens, scientists at Bar-Ilan University report on a novel experimental model that, for the first time, successfully mimics the "sleeping" and "waking" of the varicella-zoster virus. Based on neurons generated from human embryonic stem cells, and not requiring the use of experimental animals, the model allows scientists to test drugs and develop therapies to prevent shingles. It may also contribute to the fight against other viruses -- such as herpes and polio -- that target the human nervous system.

A Painful Awakening

"Most adults harbor latent VZV in their nervous system -- a 'souvenir' from a bout with childhood chickenpox," says Prof. Ronald Goldstein, a member of BIU's Mina and Everard Goodman Faculty of Life Sciences. "In one-third of people over 50, or in those with weakened immune systems, VZV re-activation triggers the localized rash, itchiness and pain of shingles. In one-third of these cases, however, shingles symptoms are far more serious, causing debilitating pain that can last for months or even years." Goldstein explains that, while an anti-shingles vaccine exists, it provides effective protection in only 50% of cases, and cannot be given to immune-compromised patients -- such as transplant recipients -- who are at particularly high risk for shingles onset.

The new model -- which makes it possible to establish stable, latent-state VZV in neurons derived from human embryonic stem cells, or hESCs -- was created by Amos Markus, a PhD student in Goldstein's lab. A major contributor to the model is Prof. Paul "Kip" Kinchington of the Departments of Ophthalmology and of Microbiology and Molecular Genetics at the University of Pittsburgh, with whom Goldstein has been collaborating closely for the past five years. An authority on the genetic modification of VZV, Kinchington made key discoveries about proteins involved in VZV activity.

The significance of this advance is in its potential impact on biomedical research; the model makes it possible to experimentally trigger re-activation of the dormant virus, to characterize the molecular processes involved, and to identify potential targets for shingles-prevention therapies.

advertisement

"We have now demonstrated hESC-derived neurons can host VZV in its dormant state in a petri dish for a period of up to seven weeks," Goldstein says, adding that dormant infections were achieved using two different methods. In the first, neurons were exposed to small amounts of viral material together with anti-viral drugs. In the second method, a drug-free micro-fluidic set-up allowed the controlled infection of neural axons, something that more closely mimics the uptake of VZV by the human nervous system in chicken pox.

"Once the infection took place, fluorescent markers allowed us to differentiate between those neurons with an active viral infection, and those in which the virus was present, but was not actively spreading," Goldstein continues. "The green-glowing cells, which were infected with dormant VZV, became our target. Our goal was to break down the cellular defenses that keep VZV quiescent -- essentially, to wake up the virus as a way of modeling what happens when latent VZV wakes up, and attacks the body in the form of shingles."

Shingles and Cellular "Shock"

According to Goldstein, shingles is frequently associated with the some immune-compromising, system-shocking event -- a linkage he has incorporated into his cell-based, experimental platform.

"Shock causes our bodies' natural defenses to falter -- whether the shock is a physical event like surgery, a ski accident, or even an emotional event, like divorce," Goldstein says. "We therefore 'shocked' the dormant virus into action by introducing events that caused the sleeping virus to wake up and become active. For VZV, this is the first time that such re-activation has been achieved in a laboratory environment."

Some Like it Cool

advertisement

A key factor in VZV re-activation revealed by the study was the critical role of temperature.

"At first, we had difficulty obtaining a robust re-activation in tissue culture," Goldstein says. "We then remembered that -- in both chicken pox and shingles -- viral replication takes place in blisters on the surface of the skin, not in internal organs. To more accurately mimic the re-activation process as it occurs in the body, we cooled our dormantly-infected human neurons down to 34 degrees centigrade -- three degrees lower than normal internal body temperature. We found that, under these cooler conditions, VZV re-activation proceeded at a much more rapid pace, with many more neurons affected.

Hitting the Snooze Button

The current model builds on previous work in which Goldstein -- a former President of the Israel Stem Cell Society who was the first researcher to successfully coax human embryonic stem cells (hESCs) into generating human peripheral sensory neurons -- showed that hESC-derived neurons can host active, infectious VZV. In these earlier studies, Goldstein also produced microscopic movies showing -- for the first time -- how VZV rapidly takes up residence within living human neurons in culture, just as it does in children with chicken pox.

Now, by creating an experimental model that mimics the transition between latency and active infection, Goldstein and his colleagues have taken another important step forward.

"We hope to use this model to develop a therapeutic method based on gene editing, which would prevent the virus from waking up and causing shingles," he says. "Such a method could be used in the treatment of patients with elevated shingles risk, such as people whose immunity has been compromised due to trauma, disease, or immunosuppressant therapies."

Goldstein points out that for the past 20 years, chicken pox vaccinations used in the West contain a live virus that can, and has, re-activated to cause shingles. The new model, in addition to providing an experimental platform for the development of a safer VZV vaccine and genetic therapies to prevent shingles, may also be useful for testing drugs and genetic engineering strategies designed to combat any virus that attacks the human nervous system.

The above-described research is supported by the US National Institutes of Health, the Israel Academy of Sciences, the US-Israel Binational Science Foundation.

make a difference: sponsored opportunity

Story Source:

Materials provided by Bar-Ilan University. Note: Content may be edited for style and length.


Journal Reference:

  1. Amos Markus, Ilana Lebenthal-Loinger, In Hong Yang, Paul R. Kinchington, Ronald S. Goldstein. An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons. PLOS Pathogens, 2015; 11 (6): e1004885 DOI: 10.1371/journal.ppat.1004885

Cite This Page:

  • MLA
  • APA
  • Chicago
Bar-Ilan University. "How dormant infections caused by childhood chicken pox can -- decades later -- trigger shingles." ScienceDaily. ScienceDaily, 4 June 2015. <www.sciencedaily.com/releases/2015/06/150604162557.htm>.
Bar-Ilan University. (2015, June 4). How dormant infections caused by childhood chicken pox can -- decades later -- trigger shingles. ScienceDaily. Retrieved October 20, 2022 from www.sciencedaily.com/releases/2015/06/150604162557.htm
Bar-Ilan University. "How dormant infections caused by childhood chicken pox can -- decades later -- trigger shingles." ScienceDaily. www.sciencedaily.com/releases/2015/06/150604162557.htm (accessed October 20, 2022).

  • RELATED TOPICS
    • Health & Medicine
      • Viruses
      • HIV and AIDS
      • Vaccines
      • Infectious Diseases
    • Plants & Animals
      • Virology
      • Developmental Biology
      • Biotechnology and Bioengineering
      • Microbiology
advertisement

  • RELATED TERMS
    • Chickenpox
    • Stem cell
    • Adult stem cell
    • Polio
    • Embryonic stem cell
    • Gene therapy
    • Epstein-Barr virus
    • Neurobiology
advertisement

  Print   Email   Share

advertisement

1

2

3

4

5
Most Popular
this week

PLANTS & ANIMALS
Eating Late Increases Hunger, Decreases Calories Burned, and Changes Fat Tissue
Dogs Can Smell When We're Stressed, Study Suggests
A New Species of Deep-Sea Fish Discovered in the Atacama Trench
EARTH & CLIMATE
Battery Tech Breakthrough Paves Way for Mass Adoption of Affordable Electric Car
Dinosaur-Killing Asteroid Triggered Global Tsunami That Scoured Seafloor Thousands of Miles from Impact Site
Collision May Have Formed the Moon in Mere Hours, Simulations Reveal
FOSSILS & RUINS
Learning About the First Animals on Earth from Life at the Poles
Reign of Papua New Guinea Highland's Megafauna Lasted Long After Humans Arrived
How Fluctuating Oxygen Levels May Have Accelerated Animal Evolution
advertisement

Strange & Offbeat
 

PLANTS & ANIMALS
How Evolution Overshot the Optimum Bone Structure in Hopping Rodents
Model Calculates Energetics of Piercing Fangs, Claws and Other Biological Weapons
The Mona Lisa Effect: How Eyespots Deter Predators That Approach from Different Directions
EARTH & CLIMATE
Methane-Eating 'Borgs' Have Been Assimilating Earth's Microbes
Impact That Killed the Dinosaurs Triggered 'Mega-Earthquake' That Lasted Weeks to Months
Ground-Breaking Research Finds Pelagic Seabirds Fly Into the Eye of the Storm When Faced With Extreme Weather Conditions
FOSSILS & RUINS
Dinosaur 'Mummies' Might Not Be as Unusual as We Think
Reign of Papua New Guinea Highland's Megafauna Lasted Long After Humans Arrived
Sound Reveals Giant Blue Whales Dance With the Wind to Find Food
Explore More
from ScienceDaily

RELATED STORIES

Common Viruses May Be Triggering the Onset of Alzheimer's Disease
July 29, 2022 — Two common viruses lie dormant in neurons -- herpes simplex virus (HSV), and varicella zoster virus (VZV). Lab models of the human brain show that activation or re-infection of VZV can trigger ...
Human Blood Cells Can Be Directly Reprogrammed Into Neural Stem Cells
Dec. 21, 2018 — Scientists have succeeded for the first time in directly reprogramming human blood cells into a previously unknown type of neural stem cell. These induced stem cells are similar to those that occur ...
Newfound Protein May Prevent Viral Infection, Herpes-Induced Cancer
Nov. 28, 2017 — A human protein has been identified that could prevent cancer by restricting a type of herpes virus from replicating. Most people are infected by several herpes viruses by the time they reach ...
Hush Little Virus, Don't Say a Word: How Scientists Investigate Sleeping Viruses
Oct. 26, 2017 — Four in five adults are infected with herpes simplex virus, say researchers, but most don't show symptoms like cold sores because the virus infection is 'latent' -- sleeping -- within the nervous ...
advertisement


SD
  • SD
    • Home Page
    • Top Science News
    • Latest News
  • Home
    • Home Page
    • Top Science News
    • Latest News
  • Health
    • View all the latest top news in the health sciences,
      or browse the topics below:
      Health & Medicine
      • Allergy
      • Alternative Medicine
      • Birth Control
      • Cancer
      • Diabetes
      • Diseases
      • Heart Disease
      • HIV and AIDS
      • Obesity
      • Stem Cells
      • ... more topics
      Mind & Brain
      • ADD and ADHD
      • Addiction
      • Alzheimer's
      • Autism
      • Depression
      • Headaches
      • Intelligence
      • Psychology
      • Relationships
      • Schizophrenia
      • ... more topics
      Living Well
      • Parenting
      • Pregnancy
      • Sexual Health
      • Skin Care
      • Men's Health
      • Women's Health
      • Nutrition
      • Diet and Weight Loss
      • Fitness
      • Healthy Aging
      • ... more topics
  • Tech
    • View all the latest top news in the physical sciences & technology,
      or browse the topics below:
      Matter & Energy
      • Aviation
      • Chemistry
      • Electronics
      • Fossil Fuels
      • Nanotechnology
      • Physics
      • Quantum Physics
      • Solar Energy
      • Technology
      • Wind Energy
      • ... more topics
      Space & Time
      • Astronomy
      • Black Holes
      • Dark Matter
      • Extrasolar Planets
      • Mars
      • Moon
      • Solar System
      • Space Telescopes
      • Stars
      • Sun
      • ... more topics
      Computers & Math
      • Artificial Intelligence
      • Communications
      • Computer Science
      • Hacking
      • Mathematics
      • Quantum Computers
      • Robotics
      • Software
      • Video Games
      • Virtual Reality
      • ... more topics
  • Enviro
    • View all the latest top news in the environmental sciences,
      or browse the topics below:
      Plants & Animals
      • Agriculture and Food
      • Animals
      • Biology
      • Biotechnology
      • Endangered Animals
      • Extinction
      • Genetically Modified
      • Microbes and More
      • New Species
      • Zoology
      • ... more topics
      Earth & Climate
      • Climate
      • Earthquakes
      • Environment
      • Geography
      • Geology
      • Global Warming
      • Hurricanes
      • Ozone Holes
      • Pollution
      • Weather
      • ... more topics
      Fossils & Ruins
      • Ancient Civilizations
      • Anthropology
      • Archaeology
      • Dinosaurs
      • Early Humans
      • Early Mammals
      • Evolution
      • Lost Treasures
      • Origin of Life
      • Paleontology
      • ... more topics
  • Society
    • View all the latest top news in the social sciences & education,
      or browse the topics below:
      Science & Society
      • Arts & Culture
      • Consumerism
      • Economics
      • Political Science
      • Privacy Issues
      • Public Health
      • Racial Disparity
      • Religion
      • Sports
      • World Development
      • ... more topics
      Business & Industry
      • Biotechnology & Bioengineering
      • Computers & Internet
      • Energy & Resources
      • Engineering
      • Medical Technology
      • Pharmaceuticals
      • Transportation
      • ... more topics
      Education & Learning
      • Animal Learning & Intelligence
      • Creativity
      • Educational Psychology
      • Educational Technology
      • Infant & Preschool Learning
      • Learning Disorders
      • STEM Education
      • ... more topics
  • Quirky
    • Top News
    • Human Quirks
    • Odd Creatures
    • Bizarre Things
    • Weird World
Free Subscriptions

Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

  • Email Newsletters
  • RSS Feeds
Follow Us

Keep up to date with the latest news from ScienceDaily via social networks:

  • Facebook
  • Twitter
  • LinkedIn
Have Feedback?

Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?

  • Leave Feedback
  • Contact Us
About This Site  |  Staff  |  Reviews  |  Contribute  |  Advertise  |  Privacy Policy  |  Editorial Policy  |  Terms of Use
Copyright 1995-2022 ScienceDaily or by other parties, where indicated. All rights controlled by their respective owners.
Content on this website is for information only. It is not intended to provide medical or other professional advice.
Views expressed here do not necessarily reflect those of ScienceDaily, its staff, its contributors, or its partners.
Financial support for ScienceDaily comes from advertisements and referral programs, where indicated.
— CCPA: Do Not Sell My Information — GDPR: Privacy Settings —