Molecular 'on/off switch' controls immune defenses against viruses

[Guest guest]

Thanks Pam

Molecular 'on/off switch' controls immune defenses

> against

> viruses

>

> Molecular 'on/off switch' controls immune defenses against viruses

>

>

> >From staff reports

> (Created: Tuesday, December 26, 2006 10:59 PM CST)

>

> DALLAS - Much like flipping a light switch, the hepatitis C virus turns

> on human immune defenses upon entering the body but also turns off those

> defenses by manipulating interaction of key cellular proteins, UT

> Southwestern Medical Center researchers have found.

>

> This same molecular " on/off switch " controls immunity against many

> viruses, highlighting a potential new target for novel therapeutics to

> fight viruses, the researchers report.

>

> In a study available online and in an upcoming issue of the " Proceedings

> of the National Academy of Sciences, " UT Southwestern scientists

> describe how the proteins RIG-I and LGP2 normally interact to turn on

> and off immune response to hepatitis C.

>

> It's known that when a virus invades a cell, the RIG-I protein triggers

> the body to generate an immune response. Once the virus has been cleared

> out, the LGP2 protein turns off the RIG-I signals.

>

> This interaction between RIG-I and LGP2 is vital for properly regulating

> immunity, but viruses such as hepatitis C can disrupt the normal process

> to shut down immune defenses early, the research team found.

>

> " This knowledge will help us design drugs that mimic the viral effects

> on these proteins to either activate a host's immune response or shut it

> down, " said Dr. Gale, associate professor of microbiology and

> the study's senior author. " This holds great potential in developing new

> disease therapies, because the tactics employed by hepatitis C to

> trigger immune response are similar to those employed by other viruses

> such as West Nile, influenza and the common cold. "

>

> Dr. Gale's research centers on studying the mechanisms viruses use to

> evade immune defenses. Of particular interest is the hepatitis C virus,

> a blood-borne infection transmitted by intravenous drug use, blood

> transfusions and sexual contact. It affects 4 million U.S. residents and

> is the nation's leading cause of cirrhosis and liver cancer.

>

> In 2005 Dr. Gale, of Carrollton, and his team completed several

> breakthrough studies on hepatitis C, discovering that the RIG-I protein

> binds to viral genetic material. Then, RIG-I changes its shape and sends

> signals to other proteins that spur production of interferon, a molecule

> that stops viral replication. The researchers also found that the virus

> launches a counterattack on RIG-I, producing a protein called a protease

> to disrupt the signaling process, preventing interferon production and

> allowing viral replication.

>

> Just how RIG-I signaling is normally regulated, however, hadn't been

> known.

>

> In the current study, UT Southwestern researchers found that RIG-I and

> LGP2 each contain a repressor domain, a sort of docking site that

> controls the actions of each protein. The domain is the key site that

> regulates the ability of RIG-I to bind to its signaling partners,

> including LGP2, acting as a switch for controlling immune response, Dr.

> Gale said.

>

> " Hepatitis C and others viruses hijack this signaling pathway to stop

> immune defenses, " he said.

>

> His research team and others are working to design novel therapeutics

> and drugs that could mimic viral effects on RIG-I to spur antiviral

> response or, conversely, mimic viral effects on LGP2 to shut down RIG-I

> activity. RIG-I shutdown would be necessary in cases when the immune

> system's response to a virus is dangerously overactive, which happened

> in many flu cases during the 1918 pandemic.

>

> " Fine-tuning immune response to infection is where antiviral or immune

> regulatory drugs are headed, " said Dr. Gale, a Cain and A.

> Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell.

>

> Other UT Southwestern researchers involved in the study were

> microbiology postdoctoral researcher and lead author Dr. Takeshi Saito;

> microbiology postdoctoral researcher Dr. Yueh-Ming Loo; graduate student

> researchers and Owen; and Dr. Sangita Sinha, an

> instructor in internal medicine. Researchers from Kyoto University and

> Osaka University in Japan also were involved in the study.

>

> The National Institutes of Health, the Burroughs Wellcome Fund and Mr.

> and Mrs. R. Batcheldor supported the study.

>

>

>

http://www.carrolltonleader.com/articles/2006/12/29/carrollton_leader/news/5insi\

de.txt

>

>

[Guest guest]

Wow, This is fascinating research Liz. Wouldn't it be great if Hep

C research led to a cure for the common cold and who knows what else.

Thanks for the post.

Lee

>

> Molecular 'on/off switch' controls immune defenses against viruses

>

> DALLAS — Dec. 25, 2006 — Much like flipping a light switch, the

> hepatitis C virus turns on human immune defenses upon entering the

> body but also turns off those defenses by manipulating interaction

of

> key cellular proteins, UT Southwestern Medical Center researchers

> have found.

>

> This same molecular " on/off switch " controls immunity against many

> viruses, highlighting a potential new target for novel

therapeutics

> to fight viruses, the researchers report.

>

> In a study available online this week and in an upcoming issue of

the

> Proceedings of the National Academy of Sciences, UT Southwestern

> scientists describe how the proteins RIG-I and LGP2 normally

interact

> to turn on and off immune response to hepatitis C.

>

> It's known that when a virus invades a cell, the RIG-I protein

> triggers the body to generate an immune response. Once the virus

has

> been cleared out, the LGP2 protein turns off the RIG-I signals.

>

> This interaction between RIG-I and LGP2 is vital for properly

> regulating immunity, but viruses such as hepatitis C can disrupt

the

> normal process to shut down immune defenses early, the research

team

> found.

>

> " This knowledge will help us design drugs that mimic the viral

> effects on these proteins to either activate a host's immune

response

> or shut it down, " said Dr. Gale, associate professor of

> microbiology and the study's senior author. " This holds great

> potential in developing new disease therapies, because the tactics

> employed by hepatitis C to trigger immune response are similar to

> those employed by other viruses such as West Nile, influenza and

the

> common cold. "

>

> Dr. Gale's research centers on studying the mechanisms viruses use

to

> evade immune defenses. Of particular interest is the hepatitis C

> virus, a blood-borne infection transmitted by intravenous drug

use,

> blood transfusions and sexual contact. It affects 4 million U.S.

> residents and is the nation's leading cause of cirrhosis and liver

> cancer.

>

> In 2005 Dr. Gale and his team completed several breakthrough

studies

> on hepatitis C, discovering that the RIG-I protein binds to viral

> genetic material. Then, RIG-I changes its shape and sends signals

to

> other proteins that spur production of interferon, a molecule that

> stops viral replication. The researchers also found that the virus

> launches a counterattack on RIG-I, producing a protein called a

> protease to disrupt the signaling process, preventing interferon

> production and allowing viral replication.

>

> Just how RIG-I signaling is normally regulated, however, hadn't

been

> known.

>

> In the current study, UT Southwestern researchers found that RIG-I

> and LGP2 each contain a repressor domain, a sort of docking site

that

> controls the actions of each protein. The domain is the key site

that

> regulates the ability of RIG-I to bind to its signaling partners,

> including LGP2, acting as a switch for controlling immune

response,

> Dr. Gale said.

>

> " Hepatitis C and others viruses hijack this signaling pathway to

stop

> immune defenses, " he said.

>

> His research team and others are working to design novel

therapeutics

> and drugs that could mimic viral effects on RIG-I to spur

antiviral

> response or, conversely, mimic viral effects on LGP2 to shut down

RIG-

> I activity. RIG-I shutdown would be necessary in cases when the

> immune system's response to a virus is dangerously overactive,

which

> happened in many flu cases during the 1918 pandemic.

>

> " Fine-tuning immune response to infection is where antiviral or

> immune regulatory drugs are headed, " said Dr. Gale.

>

> Other UT Southwestern researchers involved in the study were

> microbiology postdoctoral researcher and lead author Dr. Takeshi

> Saito; microbiology postdoctoral researcher Dr. Yueh-Ming Loo;

> graduate student researchers and Owen; and

Dr.

> Sangita Sinha, an instructor in internal medicine. Researchers

from

> Kyoto University and Osaka University in Japan also were involved

in

> the study.

>

> The National Institutes of Health, the Burroughs Wellcome Fund and

> Mr. and Mrs. R. Batcheldor supported the study.

>

[Guest guest]

If they could it would be a great place to start ....so many diseases out there that need to be dealt with ..

Re: Molecular 'on/off switch' controls immune defenses against viruses

Wow, This is fascinating research Liz. Wouldn't it be great if Hep C research led to a cure for the common cold and who knows what else.Thanks for the post.Lee>> Molecular 'on/off switch' controls immune defenses against viruses> > DALLAS — Dec. 25, 2006 — Much like flipping a light switch, the > hepatitis C virus turns on human immune defenses upon entering the > body but also turns off those defenses by manipulating interaction of > key cellular proteins, UT Southwestern Medical Center researchers > have found.> > This same molecular "on/off switch" controls immunity against many > viruses, highlighting a potential new target for novel therapeutics > to fight viruses, the researchers report.> > In a study available online this week and in an upcoming issue of the > Proceedings of the National Academy of Sciences, UT Southwestern > scientists describe how the proteins RIG-I and LGP2 normally interact > to turn on and off immune response to hepatitis C.> > It's known that when a virus invades a cell, the RIG-I protein > triggers the body to generate an immune response. Once the virus has > been cleared out, the LGP2 protein turns off the RIG-I signals.> > This interaction between RIG-I and LGP2 is vital for properly > regulating immunity, but viruses such as hepatitis C can disrupt the > normal process to shut down immune defenses early, the research team > found.> > "This knowledge will help us design drugs that mimic the viral > effects on these proteins to either activate a host's immune response > or shut it down," said Dr. Gale, associate professor of > microbiology and the study's senior author. "This holds great > potential in developing new disease therapies, because the tactics > employed by hepatitis C to trigger immune response are similar to > those employed by other viruses such as West Nile, influenza and the > common cold."> > Dr. Gale's research centers on studying the mechanisms viruses use to > evade immune defenses. Of particular interest is the hepatitis C > virus, a blood-borne infection transmitted by intravenous drug use, > blood transfusions and sexual contact. It affects 4 million U.S. > residents and is the nation's leading cause of cirrhosis and liver > cancer.> > In 2005 Dr. Gale and his team completed several breakthrough studies > on hepatitis C, discovering that the RIG-I protein binds to viral > genetic material. Then, RIG-I changes its shape and sends signals to > other proteins that spur production of interferon, a molecule that > stops viral replication. The researchers also found that the virus > launches a counterattack on RIG-I, producing a protein called a > protease to disrupt the signaling process, preventing interferon > production and allowing viral replication.> > Just how RIG-I signaling is normally regulated, however, hadn't been > known.> > In the current study, UT Southwestern researchers found that RIG-I > and LGP2 each contain a repressor domain, a sort of docking site that > controls the actions of each protein. The domain is the key site that > regulates the ability of RIG-I to bind to its signaling partners, > including LGP2, acting as a switch for controlling immune response, > Dr. Gale said.> > "Hepatitis C and others viruses hijack this signaling pathway to stop > immune defenses," he said.> > His research team and others are working to design novel therapeutics > and drugs that could mimic viral effects on RIG-I to spur antiviral > response or, conversely, mimic viral effects on LGP2 to shut down RIG-> I activity. RIG-I shutdown would be necessary in cases when the > immune system's response to a virus is dangerously overactive, which > happened in many flu cases during the 1918 pandemic.> > "Fine-tuning immune response to infection is where antiviral or > immune regulatory drugs are headed," said Dr. Gale.> > Other UT Southwestern researchers involved in the study were > microbiology postdoctoral researcher and lead author Dr. Takeshi > Saito; microbiology postdoctoral researcher Dr. Yueh-Ming Loo; > graduate student researchers and Owen; and Dr. > Sangita Sinha, an instructor in internal medicine. Researchers from > Kyoto University and Osaka University in Japan also were involved in > the study.> > The National Institutes of Health, the Burroughs Wellcome Fund and > Mr. and Mrs. R. Batcheldor supported the study.>

[Guest guest]

If they could it would be a great place to start ....so many diseases out there that need to be dealt with ..

Re: Molecular 'on/off switch' controls immune defenses against viruses

Wow, This is fascinating research Liz. Wouldn't it be great if Hep C research led to a cure for the common cold and who knows what else.Thanks for the post.Lee>> Molecular 'on/off switch' controls immune defenses against viruses> > DALLAS — Dec. 25, 2006 — Much like flipping a light switch, the > hepatitis C virus turns on human immune defenses upon entering the > body but also turns off those defenses by manipulating interaction of > key cellular proteins, UT Southwestern Medical Center researchers > have found.> > This same molecular "on/off switch" controls immunity against many > viruses, highlighting a potential new target for novel therapeutics > to fight viruses, the researchers report.> > In a study available online this week and in an upcoming issue of the > Proceedings of the National Academy of Sciences, UT Southwestern > scientists describe how the proteins RIG-I and LGP2 normally interact > to turn on and off immune response to hepatitis C.> > It's known that when a virus invades a cell, the RIG-I protein > triggers the body to generate an immune response. Once the virus has > been cleared out, the LGP2 protein turns off the RIG-I signals.> > This interaction between RIG-I and LGP2 is vital for properly > regulating immunity, but viruses such as hepatitis C can disrupt the > normal process to shut down immune defenses early, the research team > found.> > "This knowledge will help us design drugs that mimic the viral > effects on these proteins to either activate a host's immune response > or shut it down," said Dr. Gale, associate professor of > microbiology and the study's senior author. "This holds great > potential in developing new disease therapies, because the tactics > employed by hepatitis C to trigger immune response are similar to > those employed by other viruses such as West Nile, influenza and the > common cold."> > Dr. Gale's research centers on studying the mechanisms viruses use to > evade immune defenses. Of particular interest is the hepatitis C > virus, a blood-borne infection transmitted by intravenous drug use, > blood transfusions and sexual contact. It affects 4 million U.S. > residents and is the nation's leading cause of cirrhosis and liver > cancer.> > In 2005 Dr. Gale and his team completed several breakthrough studies > on hepatitis C, discovering that the RIG-I protein binds to viral > genetic material. Then, RIG-I changes its shape and sends signals to > other proteins that spur production of interferon, a molecule that > stops viral replication. The researchers also found that the virus > launches a counterattack on RIG-I, producing a protein called a > protease to disrupt the signaling process, preventing interferon > production and allowing viral replication.> > Just how RIG-I signaling is normally regulated, however, hadn't been > known.> > In the current study, UT Southwestern researchers found that RIG-I > and LGP2 each contain a repressor domain, a sort of docking site that > controls the actions of each protein. The domain is the key site that > regulates the ability of RIG-I to bind to its signaling partners, > including LGP2, acting as a switch for controlling immune response, > Dr. Gale said.> > "Hepatitis C and others viruses hijack this signaling pathway to stop > immune defenses," he said.> > His research team and others are working to design novel therapeutics > and drugs that could mimic viral effects on RIG-I to spur antiviral > response or, conversely, mimic viral effects on LGP2 to shut down RIG-> I activity. RIG-I shutdown would be necessary in cases when the > immune system's response to a virus is dangerously overactive, which > happened in many flu cases during the 1918 pandemic.> > "Fine-tuning immune response to infection is where antiviral or > immune regulatory drugs are headed," said Dr. Gale.> > Other UT Southwestern researchers involved in the study were > microbiology postdoctoral researcher and lead author Dr. Takeshi > Saito; microbiology postdoctoral researcher Dr. Yueh-Ming Loo; > graduate student researchers and Owen; and Dr. > Sangita Sinha, an instructor in internal medicine. Researchers from > Kyoto University and Osaka University in Japan also were involved in > the study.> > The National Institutes of Health, the Burroughs Wellcome Fund and > Mr. and Mrs. R. Batcheldor supported the study.>