Cellular protein hobbles HIV-1

ScienceDaily (Dec. 13, 2010) — A cellular protein called BST-2 had already been known to interfere with the spread of human immunodeficiency virus type 1 (HIV-1), by inhibiting the release of its progeny particles from infected cells. Now a team from McGill University, Montreal, shows that in addition, each progeny virion's ability to cause infection is severely impaired.

"BST-2 may exert a more potent inhibition effect on HIV-1 transmission than previously thought," says coauthor Chen Liang. The research is published in the December Journal of Virology.

BST-2 appears to attenuate infectivity of progeny particles by interfering with their maturation. Normally, during synthesis of new virus particles, a protein called PR55Gag is cleaved into three major structural proteins of HIV. "This cleavage process transforms HIV-1 from an immature and non-infectious virion into a mature and infectious virion," says Chen. The protease inhibitors, drugs given to AIDS patients to contain the disease, block this step. Similarly, BST-2 seems to interfere with this step, because in the study, its presence was associated with accumulation of uncleaved Gag precursor and intermediate products. The mechanism of that interference has yet to be elucidated.

BST-2 (bone marrow stromal cell antigen-2), also known as tetherin, is a cellular protein which has been shown to restrict production of enveloped viruses besides HIV-1, including HIV-2, simian immunodeficiency virus, Kaposi's sarcoma herpes virus, Lassa virus, Marburg virus, and Ebola virus. It interferes with release of new virus particles by anchoring one end of itself in the plasma membrane of the infected cell while the other end becomes inserted into the viral envelope.

Different viruses have evolved various countermeasures. For example, in the case of HIV-1, the viral protein Vpu downregulates BST-2 from the cell surface, removing it from virus budding sites.

"The antiviral function of BST-2 has been extensively studied by a number of groups besides ours," says Chen. "Our hope is that the results of all of these studies can eventually be used to develop a BST-2 based anti-HIV-1 therapy."

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The above story is reprinted from materials provided by American Society for Microbiology.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

J. Zhang, C. Liang. BST-2 Diminishes HIV-1 Infectivity. Journal of Virology, 2010; 84 (23): 12336 DOI: 10.1128/JVI.01228-10

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

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No More Cold Sores? Scientists Find Cellular Process That Fights Herpes Virus

ScienceDaily (Mar. 23, 2009) — Scientists have discovered a new way for our immune system to combat the elusive virus responsible for cold sores: Type 1 herpes simplex (HSV-1). As reported in the advance online edition of Nature Immunology, a group of virus hunters from the Université de Montréal, in collaboration with American colleagues, have identified a cellular process that seeks out and fights herpes.

The five-year study, partially supported by the Canadian Institutes of Health Research, was a joint project with Washington University and Pennsylvania State University.

"Once human cells are infected with Type 1 herpes simplex, the virus comes back because it hides and blocks protection from our immune system," says Luc English, the study's lead author and a doctoral student at the Université de Montréal's Department of Pathology and Cell Biology. "For the first time, our research team has identified a combative cellular mechanism in this game of hide-and-seek."

"We've found that the nuclear membrane of an infected cell can unmask Type 1 herpes simplex and stimulate the immune system to disintegrate the virus," says English.

The team made its discovery while conducting various tests in HSV-1 infected mice cells. They replicated environments when Type 1 herpes simplex thrives, namely periods of low-grade fever between 38.5 to 39 degrees, and found that herpes-fighting mechanisms were unleashed.

The research team now plans to study how activation of the herpes-combating cellular process could be applied to other illnesses. The outcome could hasten the development of therapies to prevent other immune-evading bacteria, parasites and viruses. "Our goal is to further study the molecules implicated in this mechanism to eventually develop therapies against diseases such as HIV or even cancer," says English.

According to Dr. Michel Desjardins, senior author and a professor in the Department of Pathology and Cell Biology at the Université de Montréal, treatment options might be imaginable in a decade.

"Now that we've identified the novel mechanism in cells that activate immune response to Type 1 herpes simplex, scientists are one step closer to creating new treatments that can activate the defence against this and other viruses," says Dr. Desjardins. "While it may not be possible to completely eradicate Type 1 herpes simplex in people who are already infected, at the very least, future therapies may be able to keep the virus in its dormant state."

This study was funded by the Canadian Institutes of Health Research, the Natural Science and Engineering Research Council of Canada, the Fonds de la Recherche en Santé du Québec, the U.S. National Institutes of Health and the foundation Research to Prevent Blindness.

About Herpes

There are two types of herpes viruses: Type 1 herpes simplex causes facial cold sores and Type 2 causes genital herpes. Both types of herpes affect an estimated 80 million people in America alone and there is currently no cure for the condition.

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The above story is reprinted from materials provided by University of Montreal.

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Journal Reference:

Luc English, Magali Chemali, Johanne Duron, Christiane Rondeau, Annie Laplante, Diane Gingras, Diane Alexander, David Leib, Christopher Norbury, Roger Lippé & Michel Desjardins. Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nature Immunology, 2009; DOI: 10.1038/ni.1720

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here

Cellular protein hobbles HIV-1

ScienceDaily (Nov. 16, 2010) — A cellular protein called BST-2 had already been known to interfere with the spread of human immunodeficiency virus type 1 (HIV-1), by inhibiting the release of its progeny particles from infected cells. Now a team from McGill University, Montreal, shows that in addition, each progeny virion's ability to cause infection is severely impaired.

"BST-2 may exert a more potent inhibition effect on HIV-1 transmission than previously thought," says coauthor Chen Liang. The research is published in the December Journal of Virology.

BST-2 appears to attenuate infectivity of progeny particles by interfering with their maturation. Normally, during synthesis of new virus particles, a protein called PR55Gag is cleaved into three major structural proteins of HIV. "This cleavage process transforms HIV-1 from an immature and non-infectious virion into a mature and infectious virion," says Chen. The protease inhibitors, drugs given to AIDS patients to contain the disease, block this step. Similarly, BST-2 seems to interfere with this step, because in the study, its presence was associated with accumulation of uncleaved Gag precursor and intermediate products. The mechanism of that interference has yet to be elucidated.

BST-2 (bone marrow stromal cell antigen-2), also known as tetherin, is a cellular protein which has been shown to restrict production of enveloped viruses besides HIV-1, including HIV-2, simian immunodeficiency virus, Kaposi's sarcoma herpes virus, Lassa virus, Marburg virus, and Ebola virus. It interferes with release of new virus particles by anchoring one end of itself in the plasma membrane of the infected cell while the other end becomes inserted into the viral envelope.

Different viruses have evolved various countermeasures. For example, in the case of HIV-1, the viral protein Vpu downregulates BST-2 from the cell surface, removing it from virus budding sites.

"The antiviral function of BST-2 has been extensively studied by a number of groups besides ours," says Chen. "Our hope is that the results of all of these studies can eventually be used to develop a BST-2 based anti-HIV-1 therapy."

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is reprinted from materials provided by American Society for Microbiology.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

J. Zhang, C. Liang. BST-2 Diminishes HIV-1 Infectivity. Journal of Virology, 2010; 84 (23): 12336 DOI: 10.1128/JVI.01228-10

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here