Many theories exist about why children and some adults get myocarditis,
an inflammation of the heart muscle that can cause mild to severe disease,
including death or the need for heart transplantation. The theory of a
UNMC research team is featured as the cover story in the May 15 issue of
the Journal of Infectious Diseases.
What is significant about the teams discovery is for the first time,
it allows scientists to identify a piece of coxsackievirus B that controls
its ability to grow in heart cells. That will allow us to better understand
how the virus replicates and possibly develop better treatments or vaccines
for myocarditis, said José Romero, M.D., pediatric infectious disease
specialist and senior author of the article.
Coxsackievirus is classified as a human enterovirus that occurs naturally
among human populations. It can cause flu-like symptoms. But in its worst
form, it can cause acute myocarditis, aseptic meningitis, severe infections
in newborns and severe hepatitis.
He said this is only the second time for the family of 64 enteroviruses
that scientists were able to identify a region of the viral RNA that controls
its ability to cause disease. The polio virus was the first.
The teams quest is to understand why some strains of the coxsackievirus
B are harmful while others are not.
Beginning in the summer and lasting through October, the majority of
coxsackievirus myocarditis cases will strike from 5,000 to 7,000 people,
mostly children. One-third of them will die, Dr. Romero said.
Dr. Romero said the virus is the most frequent cause of acute viral
myocarditis, a serious disease that causes inflammation of the heart muscle,
and dilated cardiomyopathy, in which the heart becomes quite large. The
problem is that not much treatment is available. About one-third of those
diagnosed with myocarditis recover, another third recover but have some
or significant damage to the heart, and the other third die.
The condition is also the cause of death of a number of people each
year who suddenly collapse and die, such as athletes.
The study is a collaboration among Dr. Romero, and authors Steven Tracy,
Ph.D., Nora Chapman, Ph.D., and former graduate students, James J. Dunn,
Ph.D., and Shelton Bradrick, Ph.D. The journal, published by the Infectious
Diseases Society of America, is the premier publication in the Western
Hemisphere for original research on the pathogenesis, diagnosis, and treatment
of infectious diseases; on the microbes that cause them; and on disorders
of host immune mechanisms. It represents physicians, scientists and other
health care professionals who specialize in infectious diseases.
Drs. Romero, Tracy and Chapman have been studying coxsackievirus and
enteroviruses since the 1980s. Several years ago, they set out to understand
why one strain of the coxsackievirus causes disease but another strain
doesnt.
In the study, they swapped the viral genetic matter (RNA) of myocarditis-causing
coxsackievirus strains with that of non-myocarditis-causing coxsackievirus
strains. Dr. Romero said the virus that could cause myocarditis grew well
in the mouse heart, whereas the non-cardiovirulent strain did not grow.
They found different strains of the virus perform differently in the mouse
heart.
A crucial interaction must occur between the virus and the heart cell
in order to cause disease, Dr. Romero said. All of these findings indicate
where we should be looking to understand more about this disease. It also
tells us whats different about different cells. We think it may be that
the virus cant copy its RNA well. It tells
us theres something inside the heart muscle cells that the virus needs
to grow.
Dr. Chapman, associate professor, pathology and microbiology, said the
team has found a tiny structure in the RNA genome critical for allowing
the virus to cause heart disease.
She said the reason the findings are important is a lot of the virus
strains dont cause disease. One of the things we want to know is if someone
gets infected with coxsackievirus, are they more likely to end up with
myocarditis, Dr. Chapman said.
One of the problems with myocarditis is few treatments are available.
An experimental drug exists, but mostly, Dr. Romero said, patients are
given supportive care such as drugs that make the heart beat stronger or
take the load off the heart. Artificial devices such as an extracorporeal
membrane oxygenation (ECMO) machine or ventricular assist device that perform
functions of the heart, also are used.
Dr. Romero said the team used a novel approach to study the virus. He
said while most experiments done for decades on the virus relied on laboratory
strains of coxsackievirus, the strains are no longer found. The team instead
used strains in the lab from humans who had disease.
The question always arises if findings in the lab really apply to clinical
situations, Dr. Romero said. Our idea was to use wild strains from
people to test and figure out what part of the virus causes cardiomyopathy.
One of the things that drew Dr. Romero to UNMC in 1993 was the research
of Drs. Tracy and Chapman. He saw several opportunities to work and learn
from them, he said.
For Dr. Romero, whose clinical and research interests have focused on
enteroviruses, specifically coxsackievirus and myocarditis, the discovery
means a lot.
What weve done is found the switch. Now we want to figure out how
the switch turns the virus on or off, he said.
The team currently is in the process of applying for funding from the
National Institutes of Health to identify the mechanism that determines
the causes of cardiomyopathy, how many cases there are, the causes and
outcomes.
Photo cutline: Murine heart histology resulting from infection with
a cardiovirulent strain of coxsackievirus B3.