Although anti-retroviral therapy is quite good at tamping down the viral load in the blood of people infected with HIV, the virus can still hang out in tissues. So researchers designed an antibody that seeks out a viral envelope protein expressed by infected cells and tacked on to this infection-homing device a toxin that destroys the cell. They tested the therapy on HIV-infected model mice and published their results in PLOS Pathogens this week (January 9).
“Everywhere we look, the antibody is able to kill those infected cells,” University of North Carolina virologist J. Victor Garcia, a leader on the study, told the Los Angeles Times. In spleen, bone marrow, liver, lung, lymph nodes, and other areas, viral DNA dropped dramatically in mice administered the antibody-poison treatment, compared to animals given only conventional antiretroviral medications. “Our work provides evidence that HIV-infected cells can be tracked down and destroyed throughout the body,” Garcia said in a statement.
John Frater, an HIV researcher from the University of Oxford, told The Conversation: “The conclusions at this stage are that in this mouse model, [antiretroviral therapy] can be potentially improved with the addition of an immunotoxin. How this translates to human treatment is not known. Also, whether this is a route for a cure strategy requires a number of other studies before any conclusions can be reached.”
Source: By Kerry Grens :- http://www.the-scientist.com/?articles.view/articleNo/38838/title/Toxin-Wipes-Out-Persistent-HIV/
Showing posts with label Science News. Show all posts
Showing posts with label Science News. Show all posts
Tuesday, January 21, 2014
Toxin Wipes Out Persistent HIV
An antibody-toxin combo kills residual HIV hiding out in the organs of mice.
Wednesday, January 9, 2013
The Glory Hole Got a Twenty-First Century Makeover
Thursday, February 26, 2009
Antiretroviral Therapy Highlights From CROI 2009
A Discussion With Joel Gallant, M.D., M.P.H.
By Bonnie Goldman
February 25, 2009
Hello and welcome. This is Bonnie Goldman, Editorial Director of TheBody.com. I'm here today with Dr. Joel Gallant. Dr. Gallant has been treating people with HIV since the beginning of the pandemic. He's also a leading HIV researcher and a professor at Johns Hopkins University School of Medicine in Baltimore, Md.
Read More...
Source:
The Body
By Bonnie Goldman
February 25, 2009
Hello and welcome. This is Bonnie Goldman, Editorial Director of TheBody.com. I'm here today with Dr. Joel Gallant. Dr. Gallant has been treating people with HIV since the beginning of the pandemic. He's also a leading HIV researcher and a professor at Johns Hopkins University School of Medicine in Baltimore, Md.
Read More...
Source:
The Body
Wealthy men give women more orgasms
From The Sunday Times
January 18, 2009
Jonathan Leake, Science and Environment Editor
Scientists have found that the pleasure women get from making love is directly linked to the size of their partner’s bank balance.
They found that the wealthier a man is, the more frequently his partner has orgasms.
“Women’s orgasm frequency increases with the income of their partner,” said Dr Thomas Pollet, the Newcastle University psychologist behind the research.
He believes the phenomenon is an “evolutionary adaptation” that is hard-wired into women, driving them to select men on the basis of their perceived quality.
The study is certain to prove controversial, suggesting that women are inherently programmed to be gold-diggers.
However, it fits into a wider body of research known as evolutionary psychology which suggests that both men and women are genetically predisposed to ruthlessly exploit each other to achieve the best chances of survival for their genes.
The female orgasm is the focus of much research because it appears to have no reproductive purpose. Women can become pregnant whatever their pleasure levels.
Pollet, and Professor Daniel Nettle, his co-author, believed, however, that the female orgasm is an evolutionary adaptation that drives women to choose and retain high-quality partners.
He and Nettle tested that idea using data gathered in one of the world’s biggest lifestyle studies. The Chinese Health and Family Life Survey targeted 5,000 people across China for in-depth interviews about their personal lives, including questions about their sex lives, income and other factors. Among these were 1,534 women with male partners whose data was the basis for the study.
They found that 121 of these women always had orgasms during sex, while 408 more had them “often”. Another 762 “sometimes” orgasmed while 243 had them rarely or never. Such figures are similar to those for western countries.
There were of course, several factors involved in such differences but, said Pollet, money was one of the main ones.
He said: “Increasing partner income had a highly positive effect on women’s self-reported frequency of orgasm. More desirable mates cause women to experience more orgasms.”
This is not an effect limited to Chinese women. Previous research in Germany and America has looked at attributes such as body symmetry and attractiveness, finding that these are also linked with orgasm frequency. Money, however, seems even more important.
David Buss, professor of psychology at the University of Texas, Austin, who raised this question in his book The Evolution of Desire believes female orgasms have several possible purposes.
“They could promote emotional bonding with a high-quality male or they could serve as a signal that women are highly sexually satisfied, and hence unlikely to seek sex with other men,” he said. “What those orgasms are saying is ‘I'm extremely loyal, so you should invest in me and my children’."
Source:
TIMESONLINE
January 18, 2009
Jonathan Leake, Science and Environment Editor
Scientists have found that the pleasure women get from making love is directly linked to the size of their partner’s bank balance.
They found that the wealthier a man is, the more frequently his partner has orgasms.
“Women’s orgasm frequency increases with the income of their partner,” said Dr Thomas Pollet, the Newcastle University psychologist behind the research.
He believes the phenomenon is an “evolutionary adaptation” that is hard-wired into women, driving them to select men on the basis of their perceived quality.
The study is certain to prove controversial, suggesting that women are inherently programmed to be gold-diggers.
However, it fits into a wider body of research known as evolutionary psychology which suggests that both men and women are genetically predisposed to ruthlessly exploit each other to achieve the best chances of survival for their genes.
The female orgasm is the focus of much research because it appears to have no reproductive purpose. Women can become pregnant whatever their pleasure levels.
Pollet, and Professor Daniel Nettle, his co-author, believed, however, that the female orgasm is an evolutionary adaptation that drives women to choose and retain high-quality partners.
He and Nettle tested that idea using data gathered in one of the world’s biggest lifestyle studies. The Chinese Health and Family Life Survey targeted 5,000 people across China for in-depth interviews about their personal lives, including questions about their sex lives, income and other factors. Among these were 1,534 women with male partners whose data was the basis for the study.
They found that 121 of these women always had orgasms during sex, while 408 more had them “often”. Another 762 “sometimes” orgasmed while 243 had them rarely or never. Such figures are similar to those for western countries.
There were of course, several factors involved in such differences but, said Pollet, money was one of the main ones.
He said: “Increasing partner income had a highly positive effect on women’s self-reported frequency of orgasm. More desirable mates cause women to experience more orgasms.”
This is not an effect limited to Chinese women. Previous research in Germany and America has looked at attributes such as body symmetry and attractiveness, finding that these are also linked with orgasm frequency. Money, however, seems even more important.
David Buss, professor of psychology at the University of Texas, Austin, who raised this question in his book The Evolution of Desire believes female orgasms have several possible purposes.
“They could promote emotional bonding with a high-quality male or they could serve as a signal that women are highly sexually satisfied, and hence unlikely to seek sex with other men,” he said. “What those orgasms are saying is ‘I'm extremely loyal, so you should invest in me and my children’."
Source:
TIMESONLINE
Wednesday, October 1, 2008
Pathologists Believe They Have Pinpointed Achilles Heel Of HIV
ScienceDaily (July 16, 2008) — Human Immunodeficiency Virus (HIV) researchers at The University of Texas Medical School at Houston believe they have uncovered the Achilles heel in the armor of the virus that continues to kill millions.
The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to Acquired Immunodeficiency Syndrome or AIDS. Normally the body’s immune defenses can ward off viruses by making proteins called antibodies that bind the virus. However, HIV is a constantly changing and mutating virus, and the antibodies produced after infection do not control disease progression to AIDS. For the same reason, no HIV preventative vaccine that stimulates production of protective antibodies is available.
The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention. Sudhir Paul, Ph.D., pathology professor in the UT Medical School, said, “Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells. If this region changes, HIV cannot infect cells. Equally important, HIV does not want this constant region to provoke the body’s defense system. So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site. Immunologists call such regions superantigens. HIV’s cleverness is unmatched. No other virus uses this trick to evade the body’s defenses.”
Paul is the senior author on a paper about this theory in a June issue of the journal Autoimmunity Reviews. Additional data supporting the theory are to be presented at the XVII International AIDS Conference Aug. 3-8 in Mexico City in two studies titled “Survivors of HIV infection produce potent, broadly neutralizing IgAs directed to the superantigenic region of the gp120 CD4 binding site” and “Prospective clinical utility and evolutionary implication of broadly neutralizing antibody fragments to HIV gp120 superantigenic epitope.”
First reported in the early 1980s, HIV has spread across the world, particularly in developing countries. In 2007, 33 million people were living with AIDS, according to a report by the World Health Organization and the United Nations.
Paul’s group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way. “The abzymes recognize essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials," Paul said.
Unlike regular antibodies, abzymes degrade the virus permanently. A single abzyme molecule inactivates thousands of virus particles. Regular antibodies inactivate only one virus particle, and their anti-viral HIV effect is weaker.
“The work of Dr. Paul’s group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function. Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection,” said Steven J. Norris, Ph.D., holder of the Robert Greer Professorship in the Biomedical Sciences and vice chair for research in the Department of Pathology and Laboratory Medicine at the UT Medical School at Houston.
The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS. Stephanie Planque, lead author and UT Medical School at Houston graduate student, said, “We discovered that disturbed immunological events in lupus patients can generate abzymes to the Achilles heel of HIV. The human genome has accumulated over millions of years of evolution a lot of viral fragments called endogenous retroviral sequences. These endogenous retroviral sequences are overproduced in people with lupus, and an immune response to such a sequence that resembles the Achilles heel can explain the production of abzymes in lupus. A small minority of HIV positive people also start producing the abzymes after decades of the infection. The immune system in some people can cope with HIV after all.”
Carl Hanson, Ph.D., who heads the Retrovirus Diagnostic Section of the Viral and Rickettsial Disease Laboratory of the California Department of Public Health, has shown that the abzymes neutralize infection of human blood cells by diverse strains of HIV from various parts of the world. Human blood cells are the only cells that HIV infects.
“This is an entirely new finding. It is a novel antibody that appears to be very effective in killing the HIV virus. The main question now is if this can be applied to developing vaccine and possibly used as a microbicide to prevent sexual transmission,” said David C. Montefiori, Ph.D., director of the Laboratory for AIDS Vaccine Research & Development at Duke University Medical Center. The abzymes are now under development for HIV immunotherapy by infusion into blood. They could also be used to guard against sexual HIV transmission as topical vaginal or rectal formulations.
“HIV is an international priority because we have no defense against it,” Paul said. “Left unchecked, it will likely evolve into even more virulent forms. We have learned a lot from this research about how to induce the production of the protective abzymes on demand. This is the Holy Grail of HIV research -- development of a preventative HIV vaccine.”
Major contributors to the research from the UT Medical School include Yasuhiro Nishiyama, Ph.D., and Hiroaki Taguchi, Ph.D., both with the Department of Pathology and Laboratory Medicine, and Miguel Escobar, M.D., of the Department of Pediatrics. Maria Salas and Hanson, both with the Viral and Rickettsial Disease Laboratory, contributed.
The research was funded by the National Institutes of Health and the Texas Higher Education Coordinating
The weak spot is hidden in the HIV envelope protein gp120. This protein is essential for HIV attachment to host cells, which initiate infection and eventually lead to Acquired Immunodeficiency Syndrome or AIDS. Normally the body’s immune defenses can ward off viruses by making proteins called antibodies that bind the virus. However, HIV is a constantly changing and mutating virus, and the antibodies produced after infection do not control disease progression to AIDS. For the same reason, no HIV preventative vaccine that stimulates production of protective antibodies is available.
The Achilles heel, a tiny stretch of amino acids numbered 421-433 on gp120, is now under study as a target for therapeutic intervention. Sudhir Paul, Ph.D., pathology professor in the UT Medical School, said, “Unlike the changeable regions of its envelope, HIV needs at least one region that must remain constant to attach to cells. If this region changes, HIV cannot infect cells. Equally important, HIV does not want this constant region to provoke the body’s defense system. So, HIV uses the same constant cellular attachment site to silence B lymphocytes - the antibody producing cells. The result is that the body is fooled into making abundant antibodies to the changeable regions of HIV but not to its cellular attachment site. Immunologists call such regions superantigens. HIV’s cleverness is unmatched. No other virus uses this trick to evade the body’s defenses.”
Paul is the senior author on a paper about this theory in a June issue of the journal Autoimmunity Reviews. Additional data supporting the theory are to be presented at the XVII International AIDS Conference Aug. 3-8 in Mexico City in two studies titled “Survivors of HIV infection produce potent, broadly neutralizing IgAs directed to the superantigenic region of the gp120 CD4 binding site” and “Prospective clinical utility and evolutionary implication of broadly neutralizing antibody fragments to HIV gp120 superantigenic epitope.”
First reported in the early 1980s, HIV has spread across the world, particularly in developing countries. In 2007, 33 million people were living with AIDS, according to a report by the World Health Organization and the United Nations.
Paul’s group has engineered antibodies with enzymatic activity, also known as abzymes, which can attack the Achilles heel of the virus in a precise way. “The abzymes recognize essentially all of the diverse HIV forms found across the world. This solves the problem of HIV changeability. The next step is to confirm our theory in human clinical trials," Paul said.
Unlike regular antibodies, abzymes degrade the virus permanently. A single abzyme molecule inactivates thousands of virus particles. Regular antibodies inactivate only one virus particle, and their anti-viral HIV effect is weaker.
“The work of Dr. Paul’s group is highly innovative. They have identified antibodies that, instead of passively binding to the target molecule, are able to fragment it and destroy its function. Their recent work indicates that naturally occurring catalytic antibodies, particularly those of the IgA subtype, may be useful in the treatment and prevention of HIV infection,” said Steven J. Norris, Ph.D., holder of the Robert Greer Professorship in the Biomedical Sciences and vice chair for research in the Department of Pathology and Laboratory Medicine at the UT Medical School at Houston.
The abzymes are derived from HIV negative people with the autoimmune disease lupus and a small number of HIV positive people who do not require treatment and do not get AIDS. Stephanie Planque, lead author and UT Medical School at Houston graduate student, said, “We discovered that disturbed immunological events in lupus patients can generate abzymes to the Achilles heel of HIV. The human genome has accumulated over millions of years of evolution a lot of viral fragments called endogenous retroviral sequences. These endogenous retroviral sequences are overproduced in people with lupus, and an immune response to such a sequence that resembles the Achilles heel can explain the production of abzymes in lupus. A small minority of HIV positive people also start producing the abzymes after decades of the infection. The immune system in some people can cope with HIV after all.”
Carl Hanson, Ph.D., who heads the Retrovirus Diagnostic Section of the Viral and Rickettsial Disease Laboratory of the California Department of Public Health, has shown that the abzymes neutralize infection of human blood cells by diverse strains of HIV from various parts of the world. Human blood cells are the only cells that HIV infects.
“This is an entirely new finding. It is a novel antibody that appears to be very effective in killing the HIV virus. The main question now is if this can be applied to developing vaccine and possibly used as a microbicide to prevent sexual transmission,” said David C. Montefiori, Ph.D., director of the Laboratory for AIDS Vaccine Research & Development at Duke University Medical Center. The abzymes are now under development for HIV immunotherapy by infusion into blood. They could also be used to guard against sexual HIV transmission as topical vaginal or rectal formulations.
“HIV is an international priority because we have no defense against it,” Paul said. “Left unchecked, it will likely evolve into even more virulent forms. We have learned a lot from this research about how to induce the production of the protective abzymes on demand. This is the Holy Grail of HIV research -- development of a preventative HIV vaccine.”
Major contributors to the research from the UT Medical School include Yasuhiro Nishiyama, Ph.D., and Hiroaki Taguchi, Ph.D., both with the Department of Pathology and Laboratory Medicine, and Miguel Escobar, M.D., of the Department of Pediatrics. Maria Salas and Hanson, both with the Viral and Rickettsial Disease Laboratory, contributed.
The research was funded by the National Institutes of Health and the Texas Higher Education Coordinating
Saturday, September 27, 2008
Scientists Unmask Key HIV Protein, Open Door For New AIDS Drugs
Latest Medical News For: HIV / AIDS
Article Date: 27 Sep 2008 - 0:00 PDT
University of Michigan scientists have provided the most detailed picture yet of a key HIV accessory protein that foils the body's normal immune response. Based on the findings, which appear online in the journal PLoS Pathogens, the team is searching for new drugs that may someday allow infected people to be cured and no longer need today's AIDS drugs for a lifetime.
"There's a big hole in current therapies, in that all of them prevent new infection, but none attack the cells that are already infected and hidden from the immune response," says Kathleen L. Collins, M.D., Ph.D., the study's senior author and a U-M associate professor in both internal medicine and microbiology and immunology.
In people infected with HIV (human immunodeficiency virus), the virus that causes AIDS, there's an unsolved problem with current anti-viral drugs. Though life-saving, they cannot root the virus out of the body. Infected cells are able to live on, undetected by the immune system, and provide the machinery for the virus to reproduce and spread.
"People have to be on the existing drugs, and when they're not, the virus rebounds. If we can develop drugs that seek out and eradicate the remaining factories for the virus, then maybe we could eradicate the disease in that person," Collins says.
Research details:
The new research details the complex actions of a protein, HIV-1 Nef, that is known to keep immune system cells from doing their normal jobs of detecting and killing infected cells.
Collins and her team show how Nef disables two key immune system players inside an infected cell. These are molecules called major histocompatability complex 1 proteins (MHC-1) that present HIV antigens to the immune system, and CD4, the cell-surface receptor that normally locks onto a virus and allows it to enter the cell.
Collins likens MHC-1 to motion detectors on a house, which send the first signal to a monitoring station if an invader breaks in.
"The immune system, especially the cytotoxic T lymphocytes, are like the monitors who get the signal that there's a foreign invader inside the cell, and send out police cars," she says. "The 'police' are toxic chemicals produced by T lymphocyte cells, which kill the cell that harbors the invader."
By in effect pushing the MHC-I proteins into an infected cell's "trash bin" so they fail to alert the T lymphocytes, Nef's actions allow active virus to hide undetected and reproduce. Also, once a cell has been infected, Nef destroys CD4. The result is that this encourages new virus to spread to uninfected cells.
Nef's activities are variable and complex. But the research team's findings suggest that the many pathways involved may end in a final common step. That could make it possible to find a drug that could block several Nef functions.
Implications:
Collins' lab is now screening drug candidates to find promising Nef inhibitors. Such drugs, which are at least 10 years away from use in people, would supplement, not replace, existing anti-viral drugs given to HIV-infected people. The new drugs would target the reservoirs where the virus hides.
In developing countries, the new drugs could have a huge impact, Collins says. Today, children born with HIV infection start taking the existing anti-HIV drugs at birth. It's very hard to continue costly treatments for a lifetime. But if children could be cured within a few years, global HIV treatment efforts could spread their dollars further and be much more successful, she says.
Additional U-M authors are first author Malinda R. Schaefer, Ph.D.; Elizabeth R. Wonderlich, Jeremiah F. Roeth and Jolie A. Leonard.
Funding for the research came from the National Institutes of Health and U-M.
Citation: PLoS Pathogens, doi:10.1371/journal.ppat.1000131
University of Michigan Health System
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
United States
http://www.med.umich.edu
Article Date: 27 Sep 2008 - 0:00 PDT
University of Michigan scientists have provided the most detailed picture yet of a key HIV accessory protein that foils the body's normal immune response. Based on the findings, which appear online in the journal PLoS Pathogens, the team is searching for new drugs that may someday allow infected people to be cured and no longer need today's AIDS drugs for a lifetime.
"There's a big hole in current therapies, in that all of them prevent new infection, but none attack the cells that are already infected and hidden from the immune response," says Kathleen L. Collins, M.D., Ph.D., the study's senior author and a U-M associate professor in both internal medicine and microbiology and immunology.
In people infected with HIV (human immunodeficiency virus), the virus that causes AIDS, there's an unsolved problem with current anti-viral drugs. Though life-saving, they cannot root the virus out of the body. Infected cells are able to live on, undetected by the immune system, and provide the machinery for the virus to reproduce and spread.
"People have to be on the existing drugs, and when they're not, the virus rebounds. If we can develop drugs that seek out and eradicate the remaining factories for the virus, then maybe we could eradicate the disease in that person," Collins says.
Research details:
The new research details the complex actions of a protein, HIV-1 Nef, that is known to keep immune system cells from doing their normal jobs of detecting and killing infected cells.
Collins and her team show how Nef disables two key immune system players inside an infected cell. These are molecules called major histocompatability complex 1 proteins (MHC-1) that present HIV antigens to the immune system, and CD4, the cell-surface receptor that normally locks onto a virus and allows it to enter the cell.
Collins likens MHC-1 to motion detectors on a house, which send the first signal to a monitoring station if an invader breaks in.
"The immune system, especially the cytotoxic T lymphocytes, are like the monitors who get the signal that there's a foreign invader inside the cell, and send out police cars," she says. "The 'police' are toxic chemicals produced by T lymphocyte cells, which kill the cell that harbors the invader."
By in effect pushing the MHC-I proteins into an infected cell's "trash bin" so they fail to alert the T lymphocytes, Nef's actions allow active virus to hide undetected and reproduce. Also, once a cell has been infected, Nef destroys CD4. The result is that this encourages new virus to spread to uninfected cells.
Nef's activities are variable and complex. But the research team's findings suggest that the many pathways involved may end in a final common step. That could make it possible to find a drug that could block several Nef functions.
Implications:
Collins' lab is now screening drug candidates to find promising Nef inhibitors. Such drugs, which are at least 10 years away from use in people, would supplement, not replace, existing anti-viral drugs given to HIV-infected people. The new drugs would target the reservoirs where the virus hides.
In developing countries, the new drugs could have a huge impact, Collins says. Today, children born with HIV infection start taking the existing anti-HIV drugs at birth. It's very hard to continue costly treatments for a lifetime. But if children could be cured within a few years, global HIV treatment efforts could spread their dollars further and be much more successful, she says.
Additional U-M authors are first author Malinda R. Schaefer, Ph.D.; Elizabeth R. Wonderlich, Jeremiah F. Roeth and Jolie A. Leonard.
Funding for the research came from the National Institutes of Health and U-M.
Citation: PLoS Pathogens, doi:10.1371/journal.ppat.1000131
University of Michigan Health System
2901 Hubbard St., Ste. 2400
Ann Arbor, MI 48109-2435
United States
http://www.med.umich.edu
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