Featured Research

from universities, journals, and other organizations

An answer to a longstanding question: How HIV infection kills T cells

Date:
November 24, 2010
Source:
Cell Press
Summary:
Researchers appear to have an explanation for a longstanding question in HIV biology: how it is that the virus kills so many CD4 T cells, despite the fact that most of them appear to be "bystander" cells that are themselves not productively infected? That loss of CD4 T cells marks the progression from HIV infection to full-blown AIDS, explain the researchers who report their findings in studies of human tonsils and spleens.

Researchers appear to have an explanation for a longstanding question in HIV biology: how it is that the virus kills so many CD4 T cells, despite the fact that most of them appear to be "bystander" cells that are themselves not productively infected. That loss of CD4 T cells marks the progression from HIV infection to full-blown AIDS, explain the researchers who report their findings in studies of human tonsils and spleens in the Nov. 24 issue of Cell, a Cell Press publication.

"In [infected] primary human tonsils and spleens, there is a profound depletion of CD4 T cells," said Warner Greene of The Gladstone institute for Virology and Immunology in San Francisco. "In tonsils, only one to five percent of those cells are directly infected, yet 99 percent of them die."

Lymphoid tissues, including tonsils and spleen, contain the vast majority of the body's CD4 T cells and represent the major site where HIV reproduces itself. And it now appears that those dying T cells aren't bystanders exactly.

The HIV virus apparently does invade those T cells, but the cells somehow block virus replication. It is the byproducts of that aborted infection that trigger an immune response that is ultimately responsible for killing those cells.

More specifically, when the virus enters the CD4 T cells that will later die, it begins to copy its RNA into DNA, Greene and his colleague Gilad Doitsh explain. That process, called reverse transcription, is what normally allows a virus to hijack the machinery of its host cell and begin replicating itself. But in the majority of those cells, the new findings show that the process doesn't come to completion.

The cells sense partial DNA transcripts as they accumulate and, in a misguided attempt to protect the body, commit a form of suicide. Greene says that completed viral transcripts in cells that are productively infected probably don't provoke the same reaction because they are so rapidly shuttled into the nucleus and integrated into the host's own DNA.

The researchers narrowed down the precise "death window" of those so-called bystander cells by taking advantage of an array of HIV drugs that act at different points in the viral life cycle. Drugs that blocked viral entry or that prevented reverse transcription altogether stopped the CD4 T cell killing, they report. Those drugs that act later in the life cycle to prevent reverse transcription only after it has already begun did not save the cells from their death.

Those cells don't die quietly either, Greene says. The cells produce ingredients that are the hallmarks of inflammation and break open, spilling all of their contents. That may provide a missing link between HIV and the inflammation that tends to go with it.

"That inflammation will attract more cells leading to more infection," Greene said. "It's a vicious cycle."

The findings also show that the CD4 T cells' demise is a response designed to be protective of the host. All that goes awry in the case of HIV and "the CD4 T cells just get blown away," compromising the immune system.

Greene said that all the available varieties of anti-HIV drugs will still work to fight the infection by preventing the virus from spreading and reducing the viral load.

The findings may lead to some new treatment strategies, however. For instance, it may be possible to develop drugs that would act on the cell sensor that triggers the immune response, helping to prevent the loss of CD 4 T cells. His team plans to explore the identity of that sensor in further studies. They also are interested to find out if the virus has strategies in place to try and prevent the CD4 T cells' death.

"The cell death pathway is really not in the virus's best interest," Greene says. "It precludes the virus from replicating and the virus may have ways to repel it."


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Journal Reference:

  1. Gilad Doitsh, Marielle Cavrois, Kara G. Lassen, Orlando Zepeda, Zhiyuan Yang, Mario L. Santiago, Andrew M. Hebbeler, Warner C. Greene. Abortive HIV Infection Mediates CD4 T Cell Depletion and Inflammation in Human Lymphoid Tissue. Cell, 2010; 143 (5): 789-801 DOI: 10.1016/j.cell.2010.11.001

Cite This Page:

Cell Press. "An answer to a longstanding question: How HIV infection kills T cells." ScienceDaily. ScienceDaily, 24 November 2010. <www.sciencedaily.com/releases/2010/11/101124124022.htm>.
Cell Press. (2010, November 24). An answer to a longstanding question: How HIV infection kills T cells. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2010/11/101124124022.htm
Cell Press. "An answer to a longstanding question: How HIV infection kills T cells." ScienceDaily. www.sciencedaily.com/releases/2010/11/101124124022.htm (accessed September 20, 2014).

Share This



More Health & Medicine News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
How The 'Angelina Jolie Effect' Increased Cancer Screenings

How The 'Angelina Jolie Effect' Increased Cancer Screenings

Newsy (Sep. 19, 2014) Angelina's Jolie's decision to undergo a preventative mastectomy in 2013 inspired many women to seek early screenings for the disease. Video provided by Newsy
Powered by NewsLook.com
The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. 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