Featured Research

from universities, journals, and other organizations

Human Protein May Offer Novel Target For Blocking HIV Infection: Successful In Lab

Date:
April 29, 2008
Source:
NIH/National Human Genome Research Institute
Summary:
A research group has uncovered a new route for attacking the human immunodeficiency virus that may offer a way to circumvent problems with drug resistance. Researchers have blocked HIV infection in the test tube by inactivating a human protein expressed in key immune cells.

Researchers report that they have blocked HIV infection in the test tube by inactivating a human protein expressed in key immune cells.
Credit: NIH

A research group supported by the National Institutes of Health (NIH) has uncovered a new route for attacking the human immunodeficiency virus (HIV) that may offer a way to circumvent problems with drug resistance. In findings published April 28 in the online edition of the Proceedings of the National Academy of Sciences, the researchers report that they have blocked HIV infection in the test tube by inactivating a human protein expressed in key immune cells.

Most of the drugs now used to fight HIV, which is the retrovirus that causes acquired immune deficiency syndrome (AIDS), target the virus's own proteins. However, because HIV has a high rate of genetic mutation, those viral targets change quickly and lead to the emergence of drug-resistant viral strains. Doctors have tried to outmaneuver the rapidly mutating virus by prescribing multi-drug regimens or switching drugs. But such strategies can increase the risk of toxic side effects, be difficult for patients to follow and are not always successful. Recently, interest has grown in attacking HIV on a new front by developing drugs that target proteins of human cells, which are far less prone to mutations than are viral proteins.

In the new study, Pamela Schwartzberg, M.D., Ph.D., a senior investigator at the National Human Genome Research Institute (NHGRI), part of NIH; Andrew J. Henderson, Ph.D., of Boston University; and their colleagues found that when they interfered with a human protein called interleukin-2-inducible T cell kinase (ITK) they inhibited HIV infection of key human immune cells, called T cells. ITK is a signaling protein that activates T cells as part of the body's healthy immune response.

"This new insight represents an important contribution to HIV research," said NHGRI Scientific Director Eric D. Green, M.D., Ph.D. "Finding a cellular target that can be inhibited so as to block HIV validates a novel concept and is an exciting model for deriving potential new HIV therapies."

When HIV enters the body, it infects T cells and takes over the activities of these white blood cells so that the virus can replicate. Eventually, HIV infection compromises the entire immune system and causes AIDS. The new work shows that without active ITK protein, HIV cannot effectively take advantage of many signaling pathways within T cells, which in turn slows or blocks the spread of the virus.

"We were pleased and excited to realize the outcome of our approach," Dr. Schwartzberg said. "Suppression of the ITK protein caused many of the pathways that HIV uses to be less active, thereby inhibiting or slowing HIV replication."

In their laboratory experiments, the researchers used a chemical inhibitor and a type of genetic inhibitor, called RNA interference, to inactivate ITK in human T cells. Then, the T cells were exposed to HIV, and the researchers studied the effects of ITK inactivation upon various stages of HIV's infection and replication cycle. Suppression of ITK reduced HIV's ability to enter T cells and have its genetic material transcribed into new virus particles. However, ITK suppression did not interfere significantly with T cells' normal ability to survive, and mice deficient in ITK were able to ward off other types of viral infection, although antiviral responses were delayed.

"ITK turns out to be a great target to examine," said Dr. Schwartzberg, noting that researchers had been concerned that blocking other human proteins involved in HIV replication might kill or otherwise impair the normal functions of T cells.

According to Dr. Schwartzberg, ITK already is being investigated as a therapeutic target for asthma and other diseases that affect immune response. In people with asthma, ITK is required to activate T cells, triggering lung inflammation and production of excess mucus.

"There are several companies who have published research about ITK inhibitors as part of their target program," Schwartzberg said. "We hope that others will extend our findings and that ITK inhibitors will be pursued as HIV therapies."

NHGRI researchers received support for this work from the NIH Intramural AIDS Targeted Antiviral Program. Chemical compounds used in the research were synthesized at the NIH Chemical Genomics Center, which was established through the NIH Roadmap for Medical Research and is administered by NHGRI. The Boston University group originally participated in the research while at Pennsylvania State University, where they received support from Penn State Tobacco Formula Funds, and where Dr. Henderson received support from the National Institute of Allergy and Infectious Diseases (NIAID).


Story Source:

The above story is based on materials provided by NIH/National Human Genome Research Institute. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Human Genome Research Institute. "Human Protein May Offer Novel Target For Blocking HIV Infection: Successful In Lab." ScienceDaily. ScienceDaily, 29 April 2008. <www.sciencedaily.com/releases/2008/04/080428175345.htm>.
NIH/National Human Genome Research Institute. (2008, April 29). Human Protein May Offer Novel Target For Blocking HIV Infection: Successful In Lab. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2008/04/080428175345.htm
NIH/National Human Genome Research Institute. "Human Protein May Offer Novel Target For Blocking HIV Infection: Successful In Lab." ScienceDaily. www.sciencedaily.com/releases/2008/04/080428175345.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
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