Study of Ebola-like Virus Affecting Fish May Lead
To Model for Predicting Viral Mutations

(WILLIAMSBURG, VA) A study of IHNV -- an Ebola-like virus that affects
fish -- may result in the development of a sophisticated model to predict
mutations of viruses, a marine scientist at the College of William and Mary
suggests. Vaccines could then be developed based on the model's
prediction of the next mutation of the virus, says Professor Stephen
Kaattari, of the college's Virginia Institute for Marine Science/School of
Marine Science (VIMS).
Death is mercifully swift for fish infected with IHNV, infectious
hematopoietic necrosis virus. Spread easily among juvenile trout and
salmon through the water, the disease kills within two weeks of initial
infection by attacking the tissues and organs and eventually causing
massive bleeding. The symptoms brought on by IHNV are almost identical to
those produced by its cousin Ebola, one of the most deadly viruses to
humans known to exist. That the viruses affect their hosts similarly may be
related to similarities in their genetic and physical structure, according
to Kaattari.
"If you stick two IHNV viruses end on end, you get what looks like
an Ebola virus," he said.
Ebola, of course, has made limited inroads into the human
population. IHNV, however, regularly ravages fish hatcheries where trout
and salmon are raised in the western United States. In any given year, the
disease can infect up to one-quarter of the hatcheries and can wipe out
entire stocks. When fish are found infected with the virus, hatchery
operators often times have no other alternative but to eliminate all the
fish and bring in a new stock. It's an approach that costs the industry
tens of millions of dollars each year in potential revenue.
For almost two years, Kaattari has been leading a team of
researchers, including graduate students, on a quest to turn the tide on
IHNV. The group is slowly beginning to uncover the dynamics of the deadly
pathogen.
Kaattari brings an array of experience in immunology to the IHNV
battle. Before coming to VIMS three years ago, Kaattari spent 11 years at
Oregon State University working on vaccines for a host of diseases that
affect fish.
While a graduate student at the University of California-Davis, Kaattari
also worked on several vaccines for humans, including a trial vaccine for a
form of ovarian cancer. The drug successfully curbed a form of cancer in
dogs, but failed to produce similar results in humans.
Those experiences provided Kaattari with a solid foundation for his
research into IHNV and the comparably destructive oyster disease Dermo,
which he is also studying intensively.
Like Dermo, IHNV is adept at thwarting vaccines and the natural
defense mechanisms of fish. Attempts at developing vaccines to protect fish
against the pathogen have failed, largely because of the virus' tendency to
mutate which can rise to a new strain. As many as 20 strains of IHNV are
known to exist. The single vaccine currently in use for IHNV protects
against only one of these strains.
Kaattari has focused much of his team's research of IHNV at the
molecular level, where the virus' weaknesses probably lie. In particular,
the scientists are trying to understand how changes in viral proteins give
rise to new strains of the virus that are resistant to the antibodies in
the fish. Their ultimate hope is to develop a model that will predict with
reasonable accuracy the next mutation of the pathogen.
To accomplish this, Kaattari's team has begun the long process of
identifying the range of antibody responses that the various IHNV strains
provoke in fish. Their goal is to isolate the antibodies, which can
neutralize the most virulent strains of the virus.
In perhaps as few as five years, Kaattari believes vaccines could
be developed based on a prediction of the next mutation of the virus.
"We think that by understanding the pressures causing the virus to
mutate, a vaccine could be designed in advance of the disease itself," said
Kaattari. "We can use this vaccine like a firebreak to cut the virus off. A
point could possibly be reached where IHNV has nowhere to go."
Kaattari, whose work is funded by a host of government agencies
including the National Institutes of Health and the U.S. Department of
Agriculture, envisions the potential for eradicating IHNV in much the same
way that smallpox was wiped out 20 years ago.
Such an approach to fighting viruses has not been employed widely
in vaccine research involving fish and humans. With this in mind, Kaattari
said his work may ultimately have a benefit to people.
"We could potentially apply the same principles in predicting the
next mutation of a virus in the fish to the development of vaccines that
protect against multiple strains of a virus in humans," said Kaattari. He
pointed to the close genetic similarity between IHNV and Ebola as evidence
that a model for predicting mutations in the fish virus could also be used
for its cousin.
Kaattari noted that the immune systems of fish respond to vaccines
in much the same way as do the immune systems of humans. Like humans, fish
also experience epidemics of disease.
The successful development of a vaccine to protect fish against
multiple strains of IHNV, added Kaattari, has potential application not
only to combating rare viruses like Ebola, but much more prevalent
pathogens such as the flu.
"Each year, new strains of influenza emerge, for which we're
constantly having to develop new vaccines," explained Kaattari. "But what
if we were to anticipate the next mutation and develop a vaccine that
addressed it and other possible new strains of the virus? We could reduce
the incidence of the disease tremendously."
While IHNV has been one of the most intensively studied fish
viruses, the body of knowledge on most fish pathogens is limited. "There
are a lot of other fish viruses just as deadly or even more so than IHNV,"
said Kaattari. "We have barely begun to scratch the surface."
Sporadic cases of IHNV have been reported in hatcheries on the East
Coast, but the disease has yet to migrate en masse from the western United
States. Kaattari and his colleagues don't know how much longer that holdoff
will last. Of greater concern to the scientists and hatchery managers is
the potential introduction of the more virulent European cousin of IHNV to
America. The virus known as VHSV, or viral
hemorrhagic septicemia virus, is thought to be more lethal to fish than
IHNV.
"It may just be a matter of luck that VHSV hasn't made it over here
yet," said Kaattari. "If it does, we could have a big problem on our
hands."

For More Information: William T. Walker, College of William and Mary (757)
221-2624.

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