By Hemesh Patel
Daily Bruin Staff
After Michael Sausser was diagnosed as HIV positive in 1988, he
started taking anti-viral drug cocktails that made him feel healthy
again.
Because he felt better, he decided to stop taking the drugs for
nine months, and as a consequence, he said the number of infected
cells in his body went through the roof.
Researchers have not been able to provide a clear explanation
for this phenomenon ““ until now.
Jerome Zack, associate director for basic sciences at the UCLA
AIDS Institute, along with David Brooks, a third-year graduate
student in the department of microbiology, immunology and molecular
genetics, have bred a mouse that allowed them to see why this
occurs.
Anti-viral medication stops the spread of infected T-cells,
often leaving a patient with undetectable levels of HIV.
T-cells normally function in the body to fight off invasions by
foreign particles. The cells develop in the thymus and travel to
other parts of the body where they remain latent, waiting to be
activated by invasive particles. HIV kills and damages cells in the
immune system.
When a patient stops taking anti-viral medication, the infected
latent T-cells, which have been growing in number all the time,
become active and the virus multiplies substantially.
The mouse Brooks and Zack developed generates a high number of
infected latent T-cells.
Zack and Brooks’ research found that, when HIV infects a
T-cell, the virus becomes latent along with the T-cell as it
travels out of the thymus.
“Nobody had shown before and identified a mechanism for
latency because these cells are so sparse,” Brooks said.
According to Zack, one in a million T-cells in a patient’s
blood is both latent and infected with the virus, but in his mouse
model, one in 10 have the virus.
Zack and his colleagues published their results in this
month’s issue of Nature Medicine.
“In the past we weren’t very sure where the virus
introduced itself into the cell to become latent,” said
Thomas Folks, chief of the HIV and Retro-virology branch of the
Center for Disease Control and Prevention.
Folks said understanding latency will be the next big hurdle
scientists must overcome in their attempts to eradicate HIV.
“To get rid of the virus, we would need to extract that
gene out,” Folks said. “We can’t get rid of a
gene in the body.”
In addition to providing scientists with a greater understanding
of virally infected latent cells, new research using the mice may
lead to drugs that will stop the spread of the virus in the
body.
“Because of this new model, we can study how the virus
behaves and we can find ways to eliminate the latent virus,”
Zack said.
Patients in the future may not have to continually take harmful
anti-viral cocktails, which lead to a number of side effects.
Zack said these drug cocktails are expensive to patients,
costing $15,000 over a 10-year span.
Sausser currently takes a combination of 27 medications, six of
which are anti-virus drugs. He takes the other 21 to counteract the
side effects of the anti-viral drugs.
When Sausser initially went off the drugs in 1988, he developed
dementia and was arrested for felony vandalism.
As a result of both the drugs he takes and the virus itself,
Sausser has developed incontinence, nausea, fatigue and is wasting
away in his arms and legs, he said.
“I’ve become disabled and I had to stop
working,” he said.
Research using the mice would hopefully find a way to eliminate
infected latent cells.
“In the absence of (drug) therapy, latency is
irrelevant,” Zack said. “It becomes a problem when a
patient gets drugs ““ it’s the low level of latency that
keeps the virus there.”
As a result, another drug could be added to the cocktail, which
would get rid of latent cells and potentially leave patients
without having to take medication.
Current anti-viral medication does not get rid of HIV, but
instead prevents it from spreading to other areas of the body.
The procedure involved transplanting human thymus cells into
mice that were bred without an immune system. Researchers then
infected the thymus tissue in the mice with HIV and used the
concentrated latent cells in their experiments.
“Understanding latent cells is really the key to finding a
cure for this disease,” Sausser said.
Mechanism for Latently Infected T-Cells Zach’s
research found a way to study this mechanism using mice. It has
potential to find new drugs to fight HIV. Original graphic by
CONNIE WU/Daily Bruin Senior Staff Web adaptation by MIKE
OUYANG/Daily Bruin