- New Research
"Do HIV-Infected Blobs Run
Amok in AIDS?"
Science News (12/19/98-12/26/98)
Vol. 145, Nos. 25 and 26, P. 391;
Some researchers believe that mobile syncytia --
collective masses of cells that aggregate during HIV infection in vitro -- may be
responsible for a number of HIV - associated disorders. While many researchers
believe that syncytia are a laboratory phenomenon, others believe the cells can lead to
leaky blood vessels and destroyed lymph nodes.
Sarah S. Frankel of the Armed Forces Institute of
Pathology in Washington, D.C., and colleagues showed in 1996 that some HIV-infected
patients had virus-containing syncytia in their adenoid tissue. Recently, Frankel
and others presented evidence at the American Society for Biology meeting in San Francisco
indicating that similar syncytia are found in lymph node and blood samples taken from HIV
- infected people. Mobile syncytia could disrupt collagen and punch holes in
endothelial tissue lining blood vessels. David R. Soll of the University of Iowa in
Iowa City explains that "syncytia are short-lived, but they're
self-perpetuating." The masses may also attract immune cells through the use of
proteins, thereby slowing down the immune system.
(SC) Study Offers New Theory On
How HIV Attacks Cells Findings contradict widely held view
San Francisco Chronicle -
Tuesday, January 5, 1999
Carl T. Hall, Chronicle Science Writer
Using a new technique for tracking the life and death of
immune cells, Bay Area AIDS researchers have found that HIV causes the deadly disease
primarily by blocking the production and shortening the survival time of
infection-fighting T cells.
That runs counter to the widely held view among AIDS
scientists that HIV strikes mainly by killing T cells, the body's front-line defenders, as
fast as the immune system can produce them.
The controversial new findings include the first direct
measurements showing how the human immune system becomes locked in a lethal battle with
the AIDS virus.
The results challenge a core tenet in the scientific
dogma of AIDS, a view that has dominated the field ever since a landmark 1995 study
co-authored by famed New York AIDS expert David Ho. The Ho group's research pictured the
AIDS virus as a virulent attacker that destroys immune cells by the millions, which spurs
a flood of new cells --which also become infected and die.
In the end, according to this view, the immune system
collapses from exhaustion. That leaves the infected victims vulnerable to all the deadly
opportunistic diseases that mark the AIDS syndrome.
The new study, published yesterday in the journal Nature
Medicine, suggests a fundamentally different process at work. The study appears along with
two separate reports on promising but very early-stage experimental approaches to treating
Taken together, the studies foretell a new generation of
immune- system targeted AIDS therapies, experts said. Given the the growing problem of
drug-resistant strains of HIV, they note, such new weapons in the AIDS battle are vitally
"We definitely need new approaches," said Dr.
Warner Greene, director of the Gladstone Institute of Virology and Immunology at the
University of California at San Francisco.
Researchers affiliated with the Gladstone Institute and
the University of California at Berkeley suggest that the previous theory, with its
presumed flurry of T-cell output, was an illusion of faulty assumptions and poor
The Bay Area scientists used a newly developed molecular
tag to track the ebb and flow of helper T cells. They spent more than a year studying
immune systems in healthy people and in 21 AIDS patients being treated at San Francisco
This produced what the authors described as the first
direct clinical measurements of immune-system activity both in AIDS patients and an
uninfected control group.
Results found no T-cell speed-up- and-collapse pattern
in the infected people. What researchers found instead was that, along with reduced cell
longevity, the virus caused slower cell production -- the opposite of what had been
assumed to occur
during this critical stage of the disease.
Just how the AIDS virus might damage T-cell production
has yet to be unraveled. And there are as yet no proven therapies to address the new view
of the disease, which would call for treatments that defend the immune system, insulating
it from HIV or making it robust enough to withstand the virus. By comparison, today's
therapies take direct aim at stopping the virus from reproducing.
AIDS experts emphasized that nothing in the study
suggests people with HIV should change their current therapy, and certainly no one should
stop taking anti-viral drug combinations now in widespread use.
But the experts said the new picture of the
"dynamics" of the disease suggests new research priorities.
"No one had really done the study in humans to
answer the true physiological questions of AIDS," said lead author Marc Hellerstein.
"Is it mainly a disease of cell production or destruction? The answer can totally
change your biological focus."
Dr. Paul Volberding, a veteran AIDS specialist at San
Francisco General, called the new cell- tracking system at the heart of the study a
"tremendously exciting" tool.
The method uses a harmless sugar molecule that can be easily detected in the DNA of the
target cells, avoiding the health risks of radioactive or chemical markers in human test
"This gives us a tool we've been waiting for for a
very long time," Volberding said.
Anthony Fauci, head of the infectious-disease branch of
the National Institutes of Health and a noted AIDS expert, said the new study is drawing
close scrutiny and could be widely influential -- if the results, which run counter to
those from other well-respected laboratories, hold up.
"This is a controversial area," Fauci said.
"I think it will remain a controversial area. It's a good paper, using an interesting
technique . . . but the jury is still out."
An editorial in Nature Medicine portrayed the
UCSF-Berkeley study as definitive evidence, but Ho indicated through a spokeswoman at the
Aaron Diamond AIDS research center in New York that he is not yet convinced. Greene, by
contrast, called the new study a "paradigm shift."
"This completely alters the way we think about the
pathogenesis of AIDS," he said.
By all accounts, the AIDS virus infects and kills T
cells. The argument is whether that's the main cause of fatal illness or if something else
is at play.
"This study tells us HIV does two things,"
said UCSF researcher Joseph McCune. "It does destroy cells, but its main affect
appears to be on the systems of cell production. What that tells us is that we have to get
rid of the virus, no question about that, but we really need to focus our attention on the
systems of cell production."
New studies of HIV at work suggest a different view of
how the virus can lead to a collapse of immune function in advanced AIDS. In the new view,
the virus directly reduces the immune system's capacity for producing new disease-fighting
T cells, rather than leading to an overactive system that ultimately exhausts itself:
Old view 1. Multiplying HIV particles
infect T cells. 2. Immune system responds by cranking up production of new T cells in an
effort to keep pace with the virus. 3. In the end stage of disease, the immune system
collapses from exhaustion.
New view 1. HIV infects mature T cells,
but not in sufficient numbers to explain how the disease progresses 2. Reseachers suspect
that the virus may attack the immune system's cell-making capacity. 3. Final stage of
disease caused primarily by collapse of immune system and reduced lifespan of T cells.