Featured Research

from universities, journals, and other organizations

St. Jude Researchers Discover Genetic Reason Why Some Patients Resist HIV Therapy

Date:
September 2, 1999
Source:
St. Jude Children's Research Hospital
Summary:
The gene MRP4 appears to help T cells, key components of the human immune system, "pump out" certain anti-HIV drugs and may allow the development of drug-resistant strains of HIV, report a team of St. Jude Children's Research Hospital scientists in the September issue of Nature Medicine.

Study sheds light on how cells evade anti-HIV drugs in absence of drug-resistant virus

(August 30, 1999) The gene MRP4 appears to help T cells, key components of the human immune system, "pump out" certain anti-HIV drugs and may allow the development of drug-resistant strains of HIV, report a team of St. Jude Children's Research Hospital scientists in the September issue of Nature Medicine.

"We have found a significant clue to explain why some HIV-infected patients resist therapy even when they have no detectable levels of drug-resistant strains of the virus," said John Schuetz, Ph.D., St. Jude pharmaceutical sciences, principal investigator of the study. Resistance to nucleoside drugs, which are the backbone of anti-HIV and other anti-viral therapy, is a serious threat to HIV patients. The team's findings could lead to developing new therapies to fight HIV infection, several viral diseases and certain cancers.

Scientists have known that drug-resistant HIV strains caused by genetic mutation have thwarted the effectiveness of drug therapy. However, for the past few years, scientists have noted HIV patients with normal forms of the virus have not responded to the standard therapy, which includes the drugs AZT, ddC, ddI, d4T, 3TC and abacavir. St. Jude scientists began looking into the cellular reasons why.

"It's like gazing into a black box. What could it be?" Schuetz said.

Their hunt for answers led them to the gene MRP4. This study is the first to describe its function. "It was just a sequence in the database prior to this," Schuetz said.

While studying T cells that were resistant to AZT and the experimental drug PMEA, researchers found that overexpression and amplification of MRP4 was responsible for drug resistance. The MRP4 protein "pumps out" nucleoside drugs from cells. Normally when nucleoside drugs enter T cells, an enzyme adds on a phosphate group -- keeping the drug in the cell so it can prevent HIV replication. In the resistant T-cells, the nucleoside drugs with mono-phosphate groups escaped from the cells, leading to lower levels of the drug. These lower concentrations of active drug are less effective in preventing replication of HIV and lead to uncontrollable proliferation of the deadly virus. Another implication of these findings -- individuals with high levels of MRP4 in their T cells may fail standard HIV drug therapy while those with low MRP4 may respond successfully to treatment.

"Now we've been able to put a handle on something," Schuetz said. "We have a bonafide cellular reason why some cells are non-responsive to conventional HIV therapy."

Now that scientists have pinpointed the problem, they can begin the search for an inhibitor that will stop MRP4 from purging drugs from T cells. This study could also shed light on the responsiveness of other diseases to nucleoside drug therapy, including Hepatitis B, cytomegalovirus, herpesvirus and cancer, Schuetz said.

St. Jude Children’s Research Hospital, in Memphis, Tennessee, was founded by the late entertainer Danny Thomas. The hospital is an internationally recognized biomedical research center dedicated to finding cures for catastrophic diseases of childhood. The hospital’s work is supported through funds raised by the American Lebanese Syrian Associated Charities (ALSAC). All St. Jude patients are treated regardless of their ability to pay. ALSAC covers all costs of treatment beyond those reimbursed by third party insurers, and total costs for families who have no insurance.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "St. Jude Researchers Discover Genetic Reason Why Some Patients Resist HIV Therapy." ScienceDaily. ScienceDaily, 2 September 1999. <www.sciencedaily.com/releases/1999/09/990902080234.htm>.
St. Jude Children's Research Hospital. (1999, September 2). St. Jude Researchers Discover Genetic Reason Why Some Patients Resist HIV Therapy. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/1999/09/990902080234.htm
St. Jude Children's Research Hospital. "St. Jude Researchers Discover Genetic Reason Why Some Patients Resist HIV Therapy." ScienceDaily. www.sciencedaily.com/releases/1999/09/990902080234.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins