Featured Research

from universities, journals, and other organizations

Discovery in how HIV thwarts the body's natural defense opens up new target for drug therapies

Date:
November 21, 2010
Source:
Rush University Medical Center
Summary:
Researchers have solved a 20-year puzzle: why natural killer cells fail to protect the body against HIV. The discovery opens up a new target for drug therapies.

Natural killer cells are major weapons in the body's immune system. They keep the body healthy by knocking off tumors and cells infected with viruses, bombarding them with tiny lethal pellets. But natural killer cells are powerless against HIV, a fact that has bedeviled science for over 20 years.

Now, researchers at Rush University Medical Center have discovered the reason why.

The study, posted online this week in the peer-reviewed journal Cell Host & Microbe, marks the "beginning of a fascinating story that will shed new light on an important but still poorly understood aspect of the interaction of HIV with natural killer cells," according to an editorial in the journal.

"With this information, we now have a major new target for drug therapies that could potentially stop HIV and allow the body's natural killer cells to do what they are designed to do -- protect the body from this lethal virus," said Edward Barker, PhD, associate professor of immunology and microbiology at Rush University and lead author of the study.

HIV, like any virus, is bent on producing progeny. It infects a cell, replicates itself over and over, and spreads throughout the body by using its "accessory" proteins to both take over the machinery of the cells it inhabits and thwart the arsenal of immunological cells that might destroy it.

Oddly, some of these proteins work at cross purposes. One, the Vpr protein, initiates what is called DNA damage repair, stopping the host cell in its tracks so that the virus can take over. But that action also sends a message to the cell surface that something is amiss. A ligand, called ULBP, is sent to the surface of the cell, which the prowling natural killer cells recognize and latch onto -- the initial steps just before moving in for a kill.

Meanwhile, another protein produced by HIV prevents the cytotoxic T cells of the immune system from homing in on the HIV-infected cell and obliterating it. But this same protein also provokes the natural killer cells into action by shutting down an inhibitory mechanism that would hold the killer cells back.

If all worked as it should to protect the body from HIV, the natural killer cells would start firing their lethal pellets. But they don't, and that is what has puzzled scientists for so long.

"The barrel of the shotgun is loaded, but the trigger still has to be pulled," said Barker.

Barker and his colleagues now know why the trigger is not pulled: because yet another protein, called NTB-A (for Natural killer T-cell and B-cell Antigen), has virtually disappeared from the surface of the infected cell. Without NTB-A in place, the natural killer cells don't start firing the guns.

The culprit, the researchers found, is a protein made by HIV called Vpu, which holds NTB-A inside the cell and prevents it from reaching the cell surface.

When the researchers altered the Vpu protein, allowing NTB-A to migrate to the cell membrane, the natural killer cells blasted the HIV-infected cells -- proof that both the ULBP ligand and NTB-A are needed before the natural killer cells will start shooting.

Barker said that the finding is extremely exciting not only because it resolves a longstanding puzzle in how HIV is able to evade the body's innate immune response but also because it opens up new possibilities for combating HIV.

Other researchers at Rush involved in the study were Anker Shah, PhD, Bharatwaj Sowrirajan, BS, Zachary Davis, BS, and Jeffrey Ward, MD, PhD. Scientists at Loyola University and the University of Utah were also involved. The research was funded by a grant from the National Institutes of Health.


Story Source:

The above story is based on materials provided by Rush University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Ankur H. Shah, Bharatwaj Sowrirajan, Zachary B. Davis, Jeffrey P. Ward, Edward M. Campbell, Vicente Planelles, Edward Barker. Degranulation of Natural Killer Cells Following Interaction with HIV-1-Infected Cells Is Hindered by Downmodulation of NTB-A by Vpu. Cell Host & Microbe, Volume 8, Issue 5, 397-409, 18 November 2010 DOI: 10.1016/j.chom.2010.10.00

Cite This Page:

Rush University Medical Center. "Discovery in how HIV thwarts the body's natural defense opens up new target for drug therapies." ScienceDaily. ScienceDaily, 21 November 2010. <www.sciencedaily.com/releases/2010/11/101119100010.htm>.
Rush University Medical Center. (2010, November 21). Discovery in how HIV thwarts the body's natural defense opens up new target for drug therapies. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2010/11/101119100010.htm
Rush University Medical Center. "Discovery in how HIV thwarts the body's natural defense opens up new target for drug therapies." ScienceDaily. www.sciencedaily.com/releases/2010/11/101119100010.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
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