- U.S. government researchers said Wednesday they have
uncovered an ingenious ploy by the shifty AIDS virus that for two decades
has thwarted intense international efforts to develop an effective vaccine
against the deadly scourge.
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- The human immunodeficiency virus, which causes acquired
immune deficiency syndrome, apparently changes shape of a critical component
of its coating to protect itself against any defenses the body can muster,
they found. The swiftly shifting strategy leaves the virus nearly invulnerable
to an antibody attack -- be it directed by the infection-intolerant immune
system or prodded by a vaccine, the scientists reported.
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- As primary defenders against disease, antibodies attach
themselves to invaders, such as HIV, each protein hooking up with its enemy
target. Just as a key fits a specific lock, so antibodies "bind"
to matching molecules on the foreign agent's surface, disabling the intruder
and sending signals to marshal other immune forces to finish the job.
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- To evade the antibody faction of the immune army, HIV
resorts to what researchers describe as conformational masking. The subterfuge
involves altering the shape of a crucial HIV protein, called gp120, throwing
up an energy barrier to sidetrack the antibodies sent to destroy it.
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- The survival tactic comes from HIV's large bag of tricks
aimed at confounding the immune system's complex network of cellular sentries,
which detect ailment- inflicting agents, and soldiers, which attack and
annihilate them, scientists said.
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- "The virus has mechanisms by which it can change
quickly to adapt to whatever immune pressures are placed upon it,"
lead study author Peter Kwong, a National Institutes of Health vaccine
researcher, said in a telephone interview. "It has such a high rate
of evolution, it may at this moment be evolving entirely new mechanisms."
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- Although the findings expose HIV as a formidable opponent,
they also suggest it is not an insurmountable one, researchers told United
Press International.
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- "These findings really develop a new concept for
immune system evasion by the virus, and researchers now have to develop
the right tools to test the concept and evaluate the possibilities for
a new vaccine," said Ted Jardetzky, Soretta and Henry Shapiro Research
Professor in Molecular Biology at Northwestern University in Evanston,
Ill., who analyzed the results.
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- "This could be a very large step towards a vaccine,
but we will only know after the ideas ... are put to the test," he
told UPI.
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- The search for a cure and an effective AIDS vaccine has
intensified with the lengthening of the global casualty list. Although
new AIDS diagnoses and deaths have plummeted in many developed countries,
the epidemic continues to rampage unabated through impoverished areas of
the Third World, particularly Sub- Saharan Africa, home to 95 percent of
the 40 million humans infected with HIV or living with the full-blown disease.
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- Last year, officials of the United States Agency for
International Development reported 5 million new HIV infections and 3 million
AIDS-related deaths worldwide. In 1999, the disease claimed 2.6 million
lives, a record at the time.
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- Since the human disease, and its monkey counterpart,
were identified in 1980, an estimated 60 million people have been infected
with the AIDS virus, and nearly half of them -- 24.8 million -- have died,
according to the U.N. AIDS program.
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- In the United States, the 20-year AIDS death toll stands
at 467,910, including 5,257 children under age 15. An estimated 320,000
Americans are living with the disease and another 500,000 are infected
with the virus, said a spokesman for the Centers for Disease Control and
Prevention in Atlanta.
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- Over the years, scientists fighting the war on AIDS have
devised an array of drug therapies that, although extending lives, do so
at a high cost -- both literally and figuratively. Expensive and causing
an array of severe side effects, the treatments exact a price that bespeaks
the need for an alternative approach.
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- Many scientists hold out hope for an AIDS vaccine that
would give the immune system a practice run in recognizing and fighting
off the hostile microbes so it could ward off the real invasion more readily.
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- Yet, this promising approach is beset with a plethora
of pitfalls.
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- "Despite two decades of research, HIV has defied
immunologists' best efforts to develop a broadly protective vaccine,"
Jardetzky pointed out.
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- Researchers using a variety of methods have developed
some two dozen experimental anti-HIV vaccines, some of which have gone
to clinical trial, but thus far the results have been disappointing.
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- In general, a vaccine should cause the immune system
to produce antibodies and/or special immune system blood cells that can
suppress or kill the infectious disease-causing organisms. In a report
published in the Dec. 12 issue of the British journal Nature, Kwong and
colleagues at the Vaccine Research Center at the National Institute of
Allergy and Infectious Diseases in Bethesda, Md., present a new explanation
of why that goal has proven elusive in AIDS vaccine research.
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- Working with human HIV and immune cells, they tracked
an unusual mechanism that appears at the root of the extraordinary evasiveness
of the resourceful and resilient organism.
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- "HIV clearly is a very unusual virus," Kwong,
chief of structural biology, told UPI. "There are not many persistent
viruses that evade the immune system to this degree."
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- A close-up look at antigenic properties of the HIV protein
gp120 provided a clue to the virus's seeming invulnerability. The protein
plays a key role in securing HIV's entry into human immune cells targeted
by the virus. The ravaging of these key infection fighters leads to a hallmark
of AIDS: a hapless defense system unable to ward off often lethal opportunistic
infections.
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- Normally, entry by an intruder triggers the production
of antibodies that recognize major features of the attacker and latch on
with a deadly grip. The rhinovirus, cause of the common cold, for instance,
stands not a prayer of surviving more than a week or two. Why don't antibodies
come to the rescue when HIV invades?
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- When in danger of being recognized by antibodies set
on its destruction, the gp120 protein changes contours at the site where
they could do the most harm, thereby diffusing the danger, the researchers
found.
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- "It took us over four years to figure this out,"
Kwong told UPI.
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- The investigators discovered a strategy that appears
to be unique to HIV: the virus erects an "energy barrier" impregnable
to the antibody contingent. By altering the shape of the viral envelope,
HIV fools the advancing antibodies and foils their attempt to put it out
of commission. The structural shift forces the antibodies to expend energy
that normally would be reserved for the attach-and-destroy mission into
recognizing and readjusting to the changed landscape at the landing site.
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- "You might compare this to countermeasures that
fighter jets use to confuse surface-to-air missile attacks," Jardetzky
explained. "If the virus is very sophisticated in its countermeasures,
we need to understand those countermeasures in detail to circumvent them
and develop new ways to attack the virus."
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- The finding marks a major advance against HIV, scientists
said.
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- "It is important for scientists, both at the fundamental
level of considering how the immune system and the virus work, and for
those scientists who are actively trying to develop practical vaccines,"
Jardetzky said. "The important message is that we are continuing to
reveal the mechanisms that make HIV so difficult to control, and this deeper
understanding of both the virus and the immune system will be important
to defeating this problem."
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