Print ArticleWashington University of St Louis report that researchers developed a method to gros norovirus in-lab, which is a first. It will lead to a better understanding of the virus and the diseases it induce (gastroenteritis or "stomach flu"). The virus is a very common cause of food poisoning. Using the in vitro cultured virus, researchers were able to determine that it had specific tropism for Macrophages and Dendritic cells, components of the immune system responsible of warning T and B cells that something is wrong (by presenting antigens, usually small peptides of degraded pathogens) and activating the immune response.
Noroviruses (genus Norovirus, family Caliciviridae) are a group of related, single-stranded RNA, nonenveloped viruses that cause acute gastroenteritis in humans. Norovirus was recently approved as the official genus name for the group of viruses provisionally described as “Norwalk-like viruses” (NLV). PLoS biology announcement
PLos Biology Paper : Replication of Norovirus in Cell Culture Reveals a Tropism for Dendritic Cells and Macrophages
More information about norovirus.
Usual Press release :
Scientists first to grow common cause of food poisoning in the lab
Nov. 30, 2004 — Scientists at Washington University School of Medicine
in St. Louis have become the first to successfully grow a norovirus in
the lab. In humans, noroviruses are a highly contagious source of
diarrhea, vomiting and other stomach upset that made headlines two
years ago after a series of repeated outbreaks on cruise ships. These
viruses are a major cause of human disease worldwide.
Researchers showed that the mouse norovirus MNV-1 could be grown inside
cells from mice with defective immune systems. Their findings make it
much easier to learn about the mouse virus and may help other
researchers seeking to duplicate the accomplishment with human forms of
the virus.
In a study published this week in the online journal Public Library of
Science-Biology, scientists who developed the new technique report it
may already have led them to a good target for vaccine development.
"By looking at the mouse virus we'd grown in the lab, we were able to
identify a part of the capsid, the virus' protein shell, that is
essential to its ability to cause disease," says senior author Skip
Virgin, M.D., Ph.D., professor of pathology and immunology and of
molecular microbiology. "If this part of the capsid has an equivalent
in human noroviruses, altering or disabling it may give us a way to
produce forms of the viruses that are weak enough to serve as
vaccines."
According to the U.S. Centers for Disease Control and Prevention,
noroviruses are involved in about half of all food poisoning cases and
annually cause about 23 million cases of acute gastroenteritis in the
United States.
Norovirus disease is characterized by frequent vomiting and diarrhea
over the course of one to two days. The most infamous norovirus, the
Norwalk virus, was first identified after a 1968 outbreak at a school
in Norwalk, Ohio. The Norwalk virus also caused a series of repeated
outbreaks on cruise ships in 2002 and in military personnel in
Afghanistan.
Although such infections rarely lead to serious or life-threatening
illness in the United States and other Western countries, they spread
rapidly, are difficult to prevent from spreading and can create
considerable discomfort. Dehydration from the diarrhea and vomiting
induced by the virus sometimes leads to hospitalization in the elderly,
the young or those with weakened immune systems. In the developing
world, these viruses are a major cause of human illness.
All previous attempts to culture human noroviruses in tissues in the
laboratory have been unsuccessful.
"As a group, noroviruses have defied characterization for decades
because there just hasn't been a way to get the virus to grow outside
of a human host," Virgin says.
In 2003, Christianne Wobus, Ph.D., and Stephanie Karst, Ph.D., two
postdoctoral fellows in Virgin's lab, identified MNV-1, the first known
mouse norovirus. Virgin's group showed that the mice's ability to fight
MNV-1 relied heavily on the innate immune system, the branch of the
immune system that attacks invaders soon after they enter the body.
In the new paper, Virgin's group reveals that MNV-1 likes to infect
cells of the innate immune system. In tests in mice, the researchers
found the virus thrived in macrophages, immune system cells that
normally engulf and destroy pathogens, and in dendritic cells,
sentry-like cells that pick up and display proteins from pathogens.
"We think there may be dendritic cells just beneath the lining of the
human gut that are providing the gateway the virus needs to cause
disease," Virgin says.
To grow the virus in the lab, researchers took dendritic cells and
macrophages from mice with defective innate immune systems and exposed
them to the virus.
"The virus grew beautifully," Virgin says. "It's a very facile and
robust system."
Comparisons of MNV-1 and human noroviruses have revealed many
similarities in gene sequence, structure and overall arrangement of the
genome. But Virgin acknowledges that differences between mouse and
human physiology may significantly alter MNV-1's interactions with its
host. For example, mice do not appear to be able to vomit.
Additionally, researchers aren't sure yet whether MNV-1 can make mice
with normal immune systems sick.
"The bottom line is that this mouse model provides us with a very
useful way to examine certain similar aspects of the noroviruses,"
Virgin says. "Among other things, we'll be using it to look at how the
capsid protein enables infection, viral replication processes and the
receptors on host cells that enable the virus to infect specific cell
types."
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