Featured Research

from universities, journals, and other organizations

Duke Researchers Discover Potent Ability Of Specific Immune System Cell Against HIV

Date:
March 28, 2000
Source:
Duke University Medical Center
Summary:
Scientists have long known that immune system cells known as "killer CD8" cells attack the AIDS virus after it enters the body by killing virus-infected cells. They also have known that CD8 cells can stop the virus from infecting new cells. Researchers now have found that CD8 cells continue to fight the virus after it enters another kind of immune system cell and begins to reproduce.

DURHAM, N.C. - Scientists have long known that immune system cells known as "killer CD8" cells attack the AIDS virus after it enters the body by killing virus-infected cells. They also have known that CD8 cells can stop the virus from infecting new cells. Researchers now have found that CD8 cells continue to fight the virus after it enters another kind of immune system cell and begins to reproduce.

Related Articles


In fact, Duke University Medical Center researchers have discovered that CD8 cells can stop human immunodeficiency virus (HIV) in its tracks even when they are added to the immune cells known as CD4 cells, which are cousins of CD8 cells in the T-cell family, after HIV has already entered the cells.

Previous work has suggested that the potency of virus suppression or number of suppressive CD8 cells could determine how quickly symptoms of AIDS develop. The new findings, reported in the March 28 issue of the Proceedings of the National Academy of Science, might point to novel protective strategies, the researchers say.

"We have known that CD8 cells are important in controlling the level of virus in the bloodstream and keeping some patients in an asymptomatic state," said Dr. Michael Greenberg of the Duke University Center for AIDS Research.

"Now for the first time, we have shown that CD8 suppressive activity also works later in the infection process, at the stage of gene expression during virus replication. Furthermore, this ability is independent of the HIV protective envelope protein.

"Stimulating the production of these virus-suppressive CD8 cells, by a vaccine or other means, could be a novel way to keep the spread of the virus under control," he said.

The Duke team's research was supported by numerous grants from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH).

An experimental system developed by a young investigator on Greenberg's team, Dr. Georgia Tomaras, was employed to provide a clearer timeline of what actually happens during an HIV infection.

After HIV enters the human body, it infects helper CD4 immune system cells because the viral envelope protein - called the gp120 glycoprotein - has a special affinity for the CD4 receptor found on these cells.

Once inside a CD4 cell, the virus' genetic material is copied into DNA and enters the nucleus, where it integrates into the host cell's DNA. From here the virus takes over the genetic machinery of the cell, directing it to produce many copies of HIV that eventually flood into the bloodstream to infect other CD4 cells. As a result of the destructive nature of HIV, the number of CD4 cells in the blood drops.

However, not all people who are infected with HIV react the same way to the virus, and much of the variability may depend on the activity of these CD8 cells.

"HIV can act very differently from person to person - some people progress to full-blown disease in a relatively short period of time, while others remain asymptomatic for many years after infection," Greenberg said. "In many of these asymptomatic patients, there appears to be strong CD8 activity. Similarly, patients who progress quickly to AIDS have very little CD8 activity."

In their experiments, the Duke researchers used blood samples taken from asymptomatic patients from Duke's Infectious Disease Clinic. The researchers developed a unique laboratory analysis that allowed them to follow in minute detail a single cycle of infection in individual CD4 cells.

In asymptomatic patients, CD8 cells can identify infected CD4 cells, latch on to them, and release compounds that cause the infected cell to burst, killing it. This cytolytic, or cell-killing, ability has been well documented.

Scientists have also known, since the discovery by Drs. Christopher Walker, Jay Levy, and colleagues at the University of California-San Francisco in the mid-1980s, that CD8 cells also possess a non-cytolytic weapon as well. However, what scientists did not know was how this non-cytolytic weapon worked to stop HIV replication.

"Experiments have shown that when the cytolytic action of CD8 cells has been blocked experimentally, viral replication is still suppressed, so the CD8 cells are still doing something," Greenberg said.

Important work by Dr. Robert Gallo's group at the University of Maryland-Baltimore demonstrated that CD8 cells release beta-chemokines that can block entry of HIV into cells. However, work by Dr. Anthony Fauci at NIH, as well as work by Levy and Greenberg, have shown that CD8 cells can also suppress HIV replication by other means. Until now, it was not known how CD8 cells accomplished this.

Greenberg's new experiments show that CD8 cells affect the virus after it has already entered the CD4 cell, which is very different from the way beta-chemokines work. The CD8 cells somehow stopped HIV from hijacking the CD4 cell's genetic machinery to reproduce itself.

To further prove this case, the Duke researchers used a system where the genetic material of HIV was encased with an envelope protein taken from a very different virus. The CD8 activity was just as strong against this "pseudotyped virus," Greenberg said, indicating that CD8's action was independent of the HIV envelope and specific to the HIV genetic material.

"These experiments are the first to show that the viral suppression occurs well after the virus enters the cell and is independent of the entry process," Greenberg explained.

The exact mechanism by which CD8 cells are able to non-cytolytically suppress viral replication is not known. According to Greenberg, the agent could be a soluble factor or a molecule on the surface of CD8 cells that transmits a biochemical signal to the CD4 cells, or a combination of both. For the first time researchers now know where in the virus life cycle to look for it, Greenberg said.

This single-cycle experimental system also yielded a rough timeline of what happens to a cell infected by HIV, and when the non-cytolytic activity of CD8 occurs. Prior experiments used systems with multiple replication cycles, making it difficult to follow actions within a single round of infection. The Duke researchers were interested in following a single life cycle.

They found that within the first two to six hours, HIV entry into CD4 cells has already been completed. Secondly, reverse transcription of the viral genetic material was finished by 10 to 14 hours. Finally, expression of early HIV genes occurs mostly between 14 to 48 hours.

With this life cycle chronology understood, the researchers could determine when during the infection process the non-cytolytic activity of the CD8 cells took place. They found if CD8 cells were added from the time of infection up to six hours after infection, viral replication was completely halted, and even after 24 hours, could achieve a significant reduction in replication.

"These experiments demonstrate that the suppressive activity of CD8 occurs later in the virus life cycle - after the virus inserts its genetic material into the genome of the target cell, but before it is completely expressed," Greenberg said. "These findings have clarified the protective role of CD8 cells."

The Duke team hopes that these findings will open new doors for scientists working on developing novel therapeutics and vaccines for HIV.

Greenberg's colleagues in the study include, from Duke, Charlene McDanal, Guido Ferrari and Kent Weinhold. Also part of the team is Simon Lacey, from the City of Hope, Duarte, Calif.


Story Source:

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


Cite This Page:

Duke University Medical Center. "Duke Researchers Discover Potent Ability Of Specific Immune System Cell Against HIV." ScienceDaily. ScienceDaily, 28 March 2000. <www.sciencedaily.com/releases/2000/03/000328085104.htm>.
Duke University Medical Center. (2000, March 28). Duke Researchers Discover Potent Ability Of Specific Immune System Cell Against HIV. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2000/03/000328085104.htm
Duke University Medical Center. "Duke Researchers Discover Potent Ability Of Specific Immune System Cell Against HIV." ScienceDaily. www.sciencedaily.com/releases/2000/03/000328085104.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) Video provided by AP
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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