Featured Research

from universities, journals, and other organizations

Bowman Gray Scientists Find Novel Way To Block AIDS Virus

Date:
October 2, 1997
Source:
Bowman Gray/Baptist Hospital Medical Center
Summary:
In what could be the most exciting advance in the treatment of AIDS to date, Bowman Gray School of Medicine scientists today reported a novel way to block the deadly HIV virus from ever invading white blood cells.

WINSTON-SALEM -- In what could be the most exciting advance in the treatment of AIDS to date, Bowman Gray School of Medicine scientists today reported a novel way to block the deadly HIV virus from ever invading white blood cells.

This new strategy, described in the Oct. 1 issue of the journal Nature Medicine, points to a fundamental new way to treat patients with HIV-1 infection or patients with Acquired Immune Deficiency Syndrome (AIDS).

This study, by Si.-Yi Chen, M.D., Ph.D., assistant professor of cancer biology, and his colleagues at Bowman Gray School of Medicine, describes how a critical co-receptor on the surface of particular white blood cells called lymphocytes is blocked, making the cells immune to infection by HIV-1.

HIV-1 virus causes AIDS by invading and destroying the white blood cells whose functions are essential to maintain the human immune system.

Chen's advance is based on the recent discovery of the critical role of chemokine receptors on the surface of the lymphocyte, as the doorway B or co-receptor B for the HIV invasion into lymphocytes.

After virus invasion, the now familiar steps in the development of AIDS follow: multiplication of the virus in the infected cells and the killing of the infected cells, progeny virus spreading to other normal lymphocytes, the decline of the disease-fighting CD4 lymphocytes and the progression to AIDS, and its ultimate downward spiral.

Last year, in another dramatic discovery, a genetic defect in a chemokine coreceptor was found to protect individuals with this defect from HIV-1 infection. These genetically defective individuals remain healthy, because the usual functions of a defective chemokine receptor can be taken over by other receptors because of redundancies in the chemokine family.

So, Chen reasoned, "genetic inactivation of the chemokine co-receptors should protect lymphocytes from HIV-1 infection and have therapeutic implications."

Chen and his colleagues set out to mimic the natural resistance of the genetically defective individuals. They designed a novel approach, termed "intracellular chemokine" -- intrakine for short -- to genetically inactivate a CXC-chemokine coreceptor, or CXCR4 for short. This CXCR4 co-receptor plays a critical role in HIV-1 fusion and entry into permissive cells, especially for T-cell line tropic HIV-1 viruses that are frequently isolated in late stages of HIV-1 infection and AIDS.

In their studies, Chen and his colleagues were able to inactivate CXCR4 through a series of steps B steps that prevent newly-produced CXCR4 deep within the lymphocyte from ever reaching the cell surface. The key is the alteration of what is known as the SDF-intrakine, which binds to the CXCR4 and traps the molecules inside the lymphocyte.

Hence there is no place on which the HIV-1 virus can land to infect the cell.

"The genetically modified lymphocytes are immune to T-tropic virus infection but appear to maintain normal biological activities," he said.

Chen said that in treating people with AIDS or HIV infection, if the process proves out, human lymphocytes would be removed from an infected patient, genetically modified with intrakine, and periodically reinfused back into patients to delay or prevent the disease progression.

"This intrakine strategy likely is superior to currently described anti-HIV approaches," said Chen, for two main reasons:

* The intrakine approach is aimed at preventing virus entry into the cell, rather than interfering with virus multiplication. Therefore, the lymphocytes protected by this approach would be truly virus-free. In contrast, all other currently described genetically based anti-HIV-1 approaches can only inhibit virus multiplication after virus infection. * This anti-HIV-1 intrakine targets a cellular chemokine receptor, rather than HIV-1 viral components. "This approach may provide a new paradigm for the treatment of HIV-1 infection, that is, to protect cells from HIV-1 infection, rather than to inhibit HIV-1 replication," Chen said. "As long as this approach can protect sufficient amounts of lymphocytes to maintain immune functions, the HIV-1-infected individuals would be healthy, even if HIV-1 viruses still replicate in the individuals." He said that since genetically modified lymphocytes can live for many months or years, "this gene-based intrakine therapy should have a potent and long-lasting anti-HIV effect."

In contrast to Chen's approach, the best current HIV treatment is with combinations or "cocktails" of drugs. While these combinations of medications shows promise of extending the lives of patients with HIV-1, Chen said, "such an approach induces toxic side effects, selects for resistant mutants, and is unlikely to completely eliminate HIV-1 from infected individuals."

Chen said, "A strategy of genetic modification of host cells, the lymphocytes or stem cells, for resistance to HIV-1 infection, together with drug therapy, may hold the ultimate hope for HIV treatment."

His group is now in the stage of pre-clinical study to further evaluate the efficacy and safety of this intrakine approach. But he said clinical trials in people are a year or more away.

The research scientists in Chen's team include Jidai Chen, M.D., Ph.D. and An-gang Yang, M.D., Ph.D. both post-doctoral fellows, and Xuefai Bai, Ph.D., a research fellow.


Story Source:

The above story is based on materials provided by Bowman Gray/Baptist Hospital Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Bowman Gray/Baptist Hospital Medical Center. "Bowman Gray Scientists Find Novel Way To Block AIDS Virus." ScienceDaily. ScienceDaily, 2 October 1997. <www.sciencedaily.com/releases/1997/10/971002065550.htm>.
Bowman Gray/Baptist Hospital Medical Center. (1997, October 2). Bowman Gray Scientists Find Novel Way To Block AIDS Virus. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/1997/10/971002065550.htm
Bowman Gray/Baptist Hospital Medical Center. "Bowman Gray Scientists Find Novel Way To Block AIDS Virus." ScienceDaily. www.sciencedaily.com/releases/1997/10/971002065550.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Man Floats for 31 Hours in Gulf Waters

Man Floats for 31 Hours in Gulf Waters

AP (Sep. 16, 2014) A Texas man is lucky to be alive after he and three others floated for more than a day in the Gulf of Mexico when their boat sank during a fishing trip. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Study Links Male-Pattern Baldness To Prostate Cancer

Study Links Male-Pattern Baldness To Prostate Cancer

Newsy (Sep. 16, 2014) New findings suggest men with a certain type of baldness at age 45 are 39 percent more likely to develop aggressive prostate cancer. 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