Featured Research

from universities, journals, and other organizations

Scientists Learn How Kaposi’s Sarcoma Virus Sabotages Immune System

Date:
July 5, 2000
Source:
University Of California, San Francisco
Summary:
A virus that causes a common form of AIDS-related cancer sabotages the body's immune system in a novel and previously unsuspected way, UCSF scientists have discovered.

A virus that causes a common form of AIDS-related cancer sabotages the body's immune system in a novel and previously unsuspected way, UCSF scientists have discovered.

When the virus associated with Kaposi's sarcoma (KS) invades a cell, two of the KS virus genes direct the cell to remove sentries posted on the cell surface and ship them to the interior for destruction, the researchers report.

The sentries -- proteins of the major histocompatibility complex, or MHC-1 -- constitute one of the cell's major lines of defense, and would otherwise tag the invaders for quick attack by the host immune system.

Other viruses sometimes disarm this line of defense too, but typically by blocking deployment of the sentries rather than getting the cell to recall them and target them for internal destruction. The approach evolved by the Kaposi's-associated herpesvirus (KSHV) is a novel strategy in the arms race between viruses and the immune system, says Donald Ganem, MD, an investigator of the Howard Hughes Medical Institute and professor of microbiology and immunology at UCSF. Ganem is senior author on a study describing the new research.

In the virus-immune system arms race, each new deployment by one side is met with a riposte from the other, Ganem says. "And there's every reason to believe this race isn't over. With every new strategy for host defense comes a selective pressure for the virus to find a way to circumvent that defense."

The research describing the KS virus genes and their function in immune sabotage is published in the current issue of the Proceedings of the National Academy of Sciences. First author is Laurent Coscoy, PhD, an HHMI postdoctoral researcher in Ganem's lab.

One of the intriguing findings in the new research is the discovery that the two proteins responsible for sequestering the MHC sentries and tagging them for destruction -- the process known as endocytosis -- do not act at the site where this action occurs, not even in the same subcellular compartment, the scientists report.

"We were surprised to discover that whereas the MHC-1 is engulfed by structures called endosomes near the surface of the cell, the viral proteins are localized in the interior of the cell, in the endoplasmic reticulum," said Coscoy.

Coscoy suggests two models for how this could occur: Either a very small population of the viral proteins -- too small to be detected experimentally -- travels to the cell membrane to cause MHC-1 to become vulnerable to the cell's endocytic machinery, or -- in a more radical proposal -- the proteins may trigger a signaling pathway from their internal location that induces the cell's surface proteins to carry out the sequestering of MHC-1.

Ganem's lab has studied KSHV since its discovery seven years ago, and was the first to successfully grow the virus in culture. In the current research, the UCSF scientists systematically examined a collection of genes that they suspected to play a role in disease induction by the virus. They tested the ability of each of these genes to reduce levels of MHC-1 in cultured cells. This identified two viral genes, called K3 and K5, that reduced MHC-1 proteins at the cell surface by 20- to 30-fold. The two genes are about 40 percent identical to one another, but are not related to any other known genes, they report.

Ganem and Coscoy are now looking at other aspects of immune function that might be modulated by the two virus genes they identified, as well as continuing to search for additional viral proteins that might impair host immunity in other ways.

Until the advent of modern antiretroviral therapies for AIDS, Kaposi's sarcoma was the most common cancer of AIDS patients. Therapies that now control the AIDS virus have also controlled KS, Ganem pointed out, because as patients become less immunodeficient they can better control the replication of KSHV -- despite the ability of KSHV to encode functions like K3 and K5. But when host defenses are somewhat impaired, further immune sabotage by proteins like K3 and K5 can help KSHV spread more widely in the patient and ultimately lead to formation of a tumor.


Story Source:

The above story is based on materials provided by University Of California, San Francisco. Note: Materials may be edited for content and length.


Cite This Page:

University Of California, San Francisco. "Scientists Learn How Kaposi’s Sarcoma Virus Sabotages Immune System." ScienceDaily. ScienceDaily, 5 July 2000. <www.sciencedaily.com/releases/2000/06/000625232411.htm>.
University Of California, San Francisco. (2000, July 5). Scientists Learn How Kaposi’s Sarcoma Virus Sabotages Immune System. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2000/06/000625232411.htm
University Of California, San Francisco. "Scientists Learn How Kaposi’s Sarcoma Virus Sabotages Immune System." ScienceDaily. www.sciencedaily.com/releases/2000/06/000625232411.htm (accessed July 24, 2014).

Share This




More Health & Medicine News

Thursday, July 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
China's Ageing Millions Look Forward to Bleak Future

China's Ageing Millions Look Forward to Bleak Future

AFP (July 24, 2014) China's elderly population is expanding so quickly that children struggle to look after them, pushing them to do something unexpected in Chinese society- move their parents into a nursing home. Duration: 02:07 Video provided by AFP
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