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The ubiquitous human herpesvirus 6 may play a
critical role in impeding the brain’s ability to
repair itself in diseases like multiple sclerosis.
The findings, which appear in the journal Scientific
Reports, may help explain the differences in
severity in symptoms that many people with the
disease experience.
“While latent HHV-6—which can be found in cells
throughout the brain—has been associated with
demyelinating disorders like multiple sclerosis it
has not been clear what role, if any, it plays in
these diseases,” says coauthor Margot Mayer-Proschel,
an associate professor at the University of
Rochester Medical Center department of biomedical
genetics.
“These findings show that, while in the process of
hiding from the immune system, the virus produces a
protein that has the potential to impair the normal
ability of cells in the brain to repair damaged
myelin.”
It is estimated that more than 80 percent of people
have been exposed to HHV-6 at some point during
their early childhood.
HHV-6 is the most common human herpesvirus and
infections that occur during childhood often go
unnoticed but the virus can cause roseola, which is
characterized by a fever and rash in infants.
A much smaller number—one percent of people—have
congenital HHV-6, where a single copy of the virus
is acquired through either the father’s sperm or
mother’s egg and is passed on to the developing
child.
While the immune system fights off the most active
forms of the infection, the virus never truly leaves
our bodies and can reactivate later in life.
The herpesvirus 6 accomplishes this form of latency
by integrating itself into our genetic code and thus
hiding in cells and evading the immune system.
One of the first studies to show an association
between latent HHV-6 infection and demyelinating
disorders took place in 2003 by URMC researchers
David Mock, M.D., who is a co-author of the current
study, Andrew Goodman, M.D. and others.
The researchers noted that HHV-6 genetic code could
be found in the brain cells of individuals with
severe forms of multiple sclerosis.
Viruses have long been suspected to contribute to
multiple sclerosis, a disorder in which the body’s
own immune system attacks and destroys myelin — the
fatty tissue that insulates the connections between
nerve cells.
However, while the 2003 study indicated that the
herpes virus played some role in multiple sclerosis,
it has subsequently become clear that the virus is
unlikely to trigger the disease.
The researchers in the current paper took a new
approach and asked instead whether the virus could
have an impact on a critical support cell found in
the brain called oligodendrocyte progenitor cells (OPCs).
These cells play an important role in maintaining
the brain’s supply of myelin.
When myelin is lost to disease, age, or injury, OPCs
are activated, migrate to where they are needed, and
mature into myelin-producing cells which repair the
damage.
The researchers examined the impact of the latent
HHV-6 on the activity of human OPCs, which was
possible through the work of Chris Proschel, a
coauthor of the paper with expertise in the
generation of human OPCs.
One of the ways the virus stays hidden in cells is
by expressing a protein called U94 that helps it
keep its place in the human DNA and remain
undetected from the immune system.
By studying human cells and transplanting human OPCs
into animal models, the team discovered that when
U94 was expressed in OPCs, the cells stopped
migrating to where they were needed.
What is still not fully understood is the
relationship between the extent of the viral
infection in the brain and the severity of diseases
like multiple sclerosis and other demyelinating
diseases such as leukodystrophies and Vanishing
White Matter disease.
For example, do the number of infected cells need to
reach a certain threshold before OPC function is
impeded?
Are individuals who have congenital HHV-6 more
vulnerable to severe forms of these diseases?
Additional coauthors are from URMC and Harvard
Medical School.
For more information
Scientific Reports
Expression of the Human Herpesvirus 6A
Latency-Associated Transcript U94A Disrupts Human
Oligodendrocyte Progenitor Migration
Andrew Campbell, Jessica M. Hogestyn, Christopher J.
Folts, Brittany Lopez, Christoph Pröschel, David
Mock & Margot Mayer-Pröschel.
Link...
University of Rochester
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