Tagged: AIDS Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 6:06 am on March 18, 2016 Permalink | Reply
    Tags: AIDS, , , TB   

    From Vandy: “Study explores gene’s role in protecting HIV patients from TB” 

    Vanderbilt U Bloc

    Vanderbilt University

    Mar. 17, 2016
    Bill Snyder
    william.snyder@Vanderbilt.Edu

    An international research team led by scientists from Vanderbilt University Medical Center has identified a genetic variant that protects people with HIV from developing active tuberculosis. The variant is near the gene encoding the infection-fighting cytokine IL-12.

    The discovery, reported this month in the American Journal of Human Genetics,could lead to new treatments for TB, which is the No. 1 killer of patients with HIV in sub-Saharan Africa and which causes more than a million deaths worldwide each year.

    HIV trimer
    HIV trimer

    “It was a very exciting finding for us, particularly in light of the potential translational implications,” said the paper’s first author, Rafal Sobota, an M.D./Ph.D. student in the Vanderbilt Medical Scientist Training Program. Sobota earned his Ph.D. in Human Genetics last year and will receive his M.D. in 2017.

    People infected with HIV, which suppresses the body’s immune system, are at higher risk of developing active TB once they are infected by the TB bacterium. Some HIV-positive people, however, do not develop active TB, even in areas such as sub-Saharan Africa, where the potentially fatal lung infection is rampant.

    To find out why, Sobota and colleagues from Dartmouth College in Hanover, New Hampshire, and Case Western Reserve University in Cleveland, conducted a genome-wide association study of 581 HIV-positive patients in Tanzania and Uganda.

    Although all participants were exposed to the TB bacterium, only 267 developed active disease over the span of at least eight years. The 314 patients who did not develop clinical TB represented an extreme resistance phenotype, which the authors believe increased the power to detect the association.

    The identified variant was in a regulatory element of the gene encoding IL-12, IL12B. Subjects with one form of the variant were protected from active TB, while those with the other form were more likely to develop active disease.

    The researchers also found that the protective variant is strongly selected for, being found in up to 45 percent of various populations in sub-Saharan Africa, while being absent in other parts of the world.

    Previous studies have shown that patients with very rare inherited IL-12 deficiency are prone to developing severe cases of active TB. And in several studies of mice infected with the TB bacterium, induction of IL12B expression or direct inoculation with the cytokine protected the animals from developing active disease.

    Sobota began the study as his dissertation topic over five years ago under the direction of his thesis advisor, Scott Williams, Ph.D., the paper’s senior author. Williams is now on the faculty at Case Western Reserve University.

    “I was fortunate enough to travel to Tanzania for six months and recruit the patients for the study,” Sobota said.

    A collaborator on the faculty at Case Western Reserve University, Catherine Stein, Ph.D., recruited the study participants in Uganda. Other co-authors included Nuri Kodaman, who also earned his Ph.D. in Human Genetics at Vanderbilt last year.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

     
  • richardmitnick 10:10 am on February 16, 2016 Permalink | Reply
    Tags: AIDS, , ,   

    From FAAH at WCG: “FightAIDS@Home Researchers Test New Simulation Methods” 

    New WCG Logo

    15 Feb 2016
    By: The FightAIDS@Home research team

    Summary
    The research team for Phase 2 of FightAIDS@Home is developing and testing new ways to use the vast computing power of World Community Grid. Their goal is to build on the results from Phase 1 while using volunteers’ resources as efficiently as possible.

    FAAH AVX101124 molecule
    This molecule, known as AVX101124, was identified in Phase 1 of FightAIDS@Home as being important to our ongoing research.

    Overview

    Our FightAIDS@Home – Phase 2 team is getting acclimated to running the research software on this very powerful yet unconventional computational resource. We are analyzing preliminary results from the first batches of research tasks, which were used to test different simulation approaches, and honing in on the most efficient ways to use the vast amount of donated computing time. We have also been preparing a large set of new work units while retooling our data processing and analysis pipelines to keep up with the massive inflow of results.

    Using BEDAM simulations for FightAIDS@Home – Phase 2 presents an enormous opportunity to refine and enrich the results from Phase I. However, before refining both hits identified in Phase 1 and new compounds studied by our HIVE Center collaborators, we need to develop and test new ways to run our software under the constraints imposed by the grid computing infrastructure.

    Details

    The current set of research tasks (‘work units’) was designed to serve three purposes. First, we evaluate how our new simulation schema tailored for free energy calculations using the distributed and heterogeneous resources of World Community Grid compares with the results of more traditional homogeneous high performance clusters. We have launched two different sets of simulations on World Community Grid that differ in how energy function parameters vary across many copies of each target ligand-protein complex being simulated. Second, the simulations allow us to revisit the calculation of binding free energies (binding scores) and prediction of binding modes (poses) for a well-studied dataset of HIV Integrase protein that we studied previously in the SAMPL4 binding free energy prediction challenge. By performing these different simulations on this benchmark set of complexes, we can design and optimize future batches of simulations to be as efficient as possible in terms of volunteers’ resources.

    The first set of simulation results (experiments 0-52) are almost complete and have been analyzed. We anticipate that this first simulation scheme is vastly superior to the second scheme being tested in experiments 53-105. We are approximately 60% through these first 106 experiments and if preliminary analysis of the second set of experiments proves our hypothesis correct, we may choose to end the second set of simulations before completion in order to move on to new batches, all using the better simulation scheme.

    Furthermore, while you’ve been crunching our work units without replication (quorum of 1), we designed the batches to have built in redundancy — which means that research tasks are assigned more than once in order to compare the results and confirm their accuracy — which we now conclude is too conservative. It is evident from analysis of the first set of batches that the current simulation protocols can be scaled down for future batches, allowing us to simulate more complexes at once on World Community Grid moving forward. We are currently preparing the next set of batches using docking results of more complexes from the SAMPL4 challenge which we recently received from the MGL laboratory at Scripps.

    We anticipate that this first year of FightAIDS@Home Phase 2 will be extremely rewarding for our group and collaborators at the HIVE Center, and we’re very grateful for having been given this opportunity by IBM, and most importantly, World Community Grid volunteers.

    It has also been an exciting month for the Levy lab. It’s our pleasure to announce that the January issue of Protein Science is a special issue in recognition of Ronald Levy’s contributions to the field of computational biophysics! The issue is free to read online. Professor Ron Levy, who designed the BEDAM tool used in this phase of the project, leads the molecular simulations in Phase 2 and we are very happy to help celebrate his accomplishments in this field.

    See the full article here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

    WCG projects run on BOINC software from UC Berkeley.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!

    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    Say No to Schistosoma

    GO Fight Against Malaria

    Drug Search for Leishmaniasis

    Computing for Clean Water

    The Clean Energy Project

    Discovering Dengue Drugs – Together

    Help Cure Muscular Dystrophy

    Help Fight Childhood Cancer

    Help Conquer Cancer

    Human Proteome Folding

    FightAIDS@Home

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
    ibm

    IBM – Smarter Planet
    sp

     
  • richardmitnick 12:43 pm on January 14, 2016 Permalink | Reply
    Tags: AIDS, ,   

    From Scripps: “Getting closer to an HIV Vaccine” 

    Scripps
    Scripps Research Institute

    January 2016
    No writer credit found

    1
    Authors of the new paper [no paper reference in article] included (left to right) James Voss, Raiees Andrabi, Dennis Burton, Bryan Briney and Chi-Hui Liang.

    For more than 30 years, an effective vaccine against HIV has eluded scientists, and more than two million people are still newly infected with the virus each year. In a recent study, scientists at The Scripps Research Institute gained a new weapon in that long fight. They identified four antibodies targeting a specific weak spot on HIV that provided key information for the design of a potential HIV vaccine candidate.

    “This study [no paper reference in article]is an example of how we can learn from natural infection and translate that information into vaccine development,” said TSRI Research Associate Raiees Andrabi. “This is an important advance in the field of antibody-based HIV vaccine development.”

    Dr. Andrabi served as first author of the study, working in the lab of senior author TSRI Professor Dennis R. Burton, who is also scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI.

    The findings build on the success of several recent TSRI studies showing that, with prompting, the immune system can develop antibodies to neutralize many strains of HIV. In the new study, the researchers carried out a series of experiments involving virus modifications and protein and antibody engineering. They found that four antibodies targeted a single spot on HIV’s surface called the V2 apex. This was significant because the V2 apex could be recognized by these antibodies on about 90 percent of known HIV strains – and even related strains that infect other species, meaning a vaccine that targets this region could protect against many forms of the virus.

    “This region helps stabilize the virus, so it’s an important area to target if you want to neutralize HIV,” said Dr. Andrabi.

    Investigating further, the researchers noticed that two of the four antibodies had an unusual feature that could prove important in vaccine design. The immune system usually begins its fight against infection by activating immune B cells that express “germline” forms of antibodies on their surface to bind invading pathogens. Germline antibodies rarely bind viruses very effectively themselves; instead, they are precursors for more developed antibodies, which mutate and hone their response to the invader.

    Yet in the new study, two of the antibodies did not need to mutate to bind with the V2 apex; instead, these antibodies used part of their basic germline structure, encoded by non-mutated genes. This means any patient with HIV should, in theory, have the ability to kick-start the right immune response.

    To generate that response, it was critical for the scientists to find the right proteins in HIV that the antibodies could recognize and bind to. In the new study, the researchers succeeded in mimicking a structure on HIV called the native HIV coat protein. This enabled them to design proteins that do indeed bind well to the germline antibodies and hopefully start a useful immune response. The next step will be to test the vaccine candidates in animal models.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 9:43 pm on December 28, 2015 Permalink | Reply
    Tags: AIDS, ,   

    From UC Davis: “Turning the Tables on Hidden HIV” 

    Temp 1

    Thirty years ago, contracting HIV was a death sentence.

    The virus attacks the immune system, specifically T-cells, until immunity breaks down completely. Patients would eventually develop AIDS, and ultimately succumb to opportunistic infections.

    The development of highly active antiretroviral therapies or HAART changed all that, converting a deadly disease into a chronic one. As long as patients stayed on the drug regimen, they could live normal lifespans. Their immune systems would recover and viral levels would decline to nearly zero.

    But there’s a catch. Nearly zero is not the same as zero. HIV has a latency mode, during which the virus is dormant – evading both HAART and the body’s immune system. Remove HAART treatment, and the virus comes roaring back.

    That means a lifetime consuming powerful and expensive treatments – if one’s body and health status can tolerate them in the first place. And no one knows how the drugs will affect patients after 20, 30 or 40 years.

    “We’ve made great progress, but at the end of the day you still have more than 30 million people living with HIV,” says Satya Dandekar, professor and chair of the UC Davis Department of Medical Microbiology and Immunology. “Without drugs, the virus can come back at the same threat level for patients.

    “Actually eradicating HIV is extremely critical.”

    For decades, UC Davis researchers have worked with that ultimate goal in mind. Scientists have learned important details about how HIV operates along the way; for example, that it first attacks immune cells in the gut.

    But now we’ve reached a new stage in the battle against HIV. The goal is no longer to control the disease, but to cure it. Two UC Davis groups are beginning clinical trials in hopes of doing just that.

    Shock and kill

    It would be hard to overstate the significance of HIV latency. The virus’s ability to evade treatment has made it difficult, if not impossible, to cure. The challenge for clinicians is to identify a two-pronged strategy: shock the latent virus out of hibernation, and hit it with immune treatments to kill it.

    2
    No image credit found

    Dandekar, along with dermatologist Emanual Maverakis, are about to test the first part of that strategy. Just a few months ago, the Dandekar lab identified several agents that “wake up” HIV. One in particular, PEP005, has shown striking results. Even better, the drug is already approved by the U.S. Food and Drug Administration.

    “We found this was really effective at reactivating HIV and works beautifully with other latency reactivating agents,” says Dandekar. “The thing that’s really exciting is that the molecule is in the drug PICATO, which treats skin cancer. It’s already approved and being used by patients.”

    Now the UC Davis group hopes to extend PICATO’s uses to attacking HIV latency as well, and is launching a small clinical trial to test the drug’s safety in HIV patients. If the trial is successful, the team hopes to combine PICATO, and other drugs that reactivate HIV, with immunotherapies that would destroy the virus as it comes out of hiding.

    “It will have to be a combination,” says Dandekar. “Just reactivating HIV from latency won’t be enough. We need to position the patient so those reactivated cells can be cleared.”

    Reboot the system

    UC Davis researchers are moving another promising approach into clinical trials as well. It involves taking blood stem cells from patients, genetically engineering them with anti-HIV genes, and returning them to the patients – essentially “rebooting” their immune systems and empowering them to eradicate or adequately suppress remaining HIV on their own over the long term.

    “We are using our understanding of basic HIV biology to engineer each patient’s own stem cells to fight the virus,” says Joseph Anderson, an assistant adjunct professor who researches infectious diseases at the UC Davis Institute for Regenerative Cures, the university’s main stem cell research center. “We’re hoping that by reintroducing these cells in a bone marrow transplant, we can rebuild the immune system to resist HIV.”

    Temp 3

    Anderson and Mehrdad Abedi, a hematology professor and stem cell transplant specialist, are trying to replicate the treatment that cured Timothy Brown, also known as the “Berlin Patient.” Brown received a stem cell transplant from a donor whose genome contained an HIV-resistant mutation. That was seven years ago – and Brown remains HIV-free.

    Anderson, who has been investigating anti-HIV genes since he was a Ph.D. student, is using three different genes to attack the virus, each one hitting a different mechanism associated with HIV infection. Like the drug cocktails used for HAART, multiple attack vectors may reduce the virus’s ability to evade treatment.

    But a new key to the UC Davis team’s gene therapy strategy is also an improved viral vector that Anderson developed to help boost the treatment’s potency. The vector contains a gene that “tags” the surface of the stem cells that are HIV-resistant, allowing researchers to maximize their volume and potential power by culling out non-resistant cells before transplantation.

    Anderson and Abedi have received an $8.5 million grant from the state’s stem cell agency, the California Institute for Regenerative Medicine or CIRM, to conduct the trial. The study will test the engineered stem cells in patients with HIV-related lymphoma, since they already require bone marrow transplants to treat their cancer. This trial will also test the therapy’s safety.

    The team hopes the treatment will be a complete cure, but even a partial response would be great news for HIV patients.

    “Maybe we won’t be able to eradicate it in some patients,” said Anderson, “but hopefully we are giving them enough of an HIV-resistant immune system that they can live the rest of their lives without having to take the antiretroviral drugs.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    UC Davis Campus

    The University of California, Davis, is a major public research university located in Davis, California, just west of Sacramento. It encompasses 5,300 acres of land, making it the second largest UC campus in terms of land ownership, after UC Merced.

     
  • richardmitnick 2:27 pm on October 15, 2015 Permalink | Reply
    Tags: AIDS, ,   

    From Brown: “Team describes rapid, sensitive test for HIV mutations” 

    Brown University
    Brown University

    October 15, 2015
    David Orenstein
    david_orenstein@brown.edu
    401-863-1862

    1
    RNA reconnaissance
    A Brown team has developed a new method for analyzing the the RNA (green strands) of HIV for mutations (red dot) that convey drug resistance. The system does not require transcription of RNA to DNA, as current technologies do, and works. Image: Lei Zhang/Brown University

    Tests that can distinguish whether HIV-positive people are infected with a drug-resistant strain or a non-resistant strain allow patients to get the most effective treatment as quickly as possible. In the November edition of the Journal of Molecular Diagnostics, a team of Brown University researchers describes a new method that works faster and more sensitively in lab testing than the current standard technologies.

    The main advance enabling that improved performance is that the system operates directly on the virus’ more readily available RNA rather than requiring extra, potentially error-prone steps to examine DNA derived from RNA. In a single tube, the system can first combine two engineered probes (ligation) if a mutation is present and then make many copies of those combined probes (amplification) for detection.

    “LRA (ligation on RNA amplification) uniquely optimizes two enzymatic reactions — RNA-based ligation, and quantitative PCR (polymerase chain reaction) amplification — into a single system,” said Anubhav Tripathi, professor of engineering at Brown and corresponding author on the paper. “Each HIV contains about 10,000 nucleotides, or building blocks, in its genetic material, and a drop of blood from a patient with resistant HIV can contain thousands to millions of copies of HIV. To find that one virus, out of thousands to millions, which is mutated at just a single nucleotide is like finding a needle in a haystack.”

    The experiments reported in the paper show that the LRA test was sensitive enough to find a commonly sought K103N mutation in concentrations as low as one mutant per 10,000 strands of “normal” viral RNA. The LRA detection worked within two hours, while alternative technologies such as ASPCR or pyrosequencing, can take as long as eight.

    LRA works by sending in many copies of a pair of short engineered probes of genetic material to complement the RNA in the HIV sample. Under optimized conditions, those pairs that perfectly match the target HIV RNA containing a mutation that causes drug resistance can rapidly become fused together, or ligated, by an enzyme. If there is a single nucleotide difference, the pair won’t fuse.

    The fusing of the engineered genetic probes is designed to happen at room temperature. After a short period, the LRA system then heats the slightly alkaline solution, which shuts off the fusing reaction but turns on the amplification (copying) of fused pairs. That allows the LRA system to produce a strong signal of fused pairs, if there are any. All this happens in a single step, without any need to change solution.

    Aiming for the clinic

    The development of LRA is the product of a collaboration led by Tripathi and Dr. Rami Kantor, associate professor of medicine in the Warren Alpert Medical School. Kantor, who is also an HIV specialist at The Miriam Hospital and co-senior author of the paper, works in developing nations such as Kenya and India, monitoring HIV resistance. One day when Tripathi was at the Lifespan/Tufts/Brown Center for AIDS Research Retrovirology Core Laboratory to discuss his work, Kantor suggested a collaboration with the end goal of developing a cheap, quick and accurate HIV drug resistance mutation detection system for use in developing nations.

    “We met soon thereafter and started working together on various developments and implementations of the ideas and on the integration of our worlds,” Kantor said.

    The authors acknowledge in the paper that what they demonstrate, while successful in the lab, is clearly not ready for deployment in the field. The lab tests, for example, are shown to work on HIV RNA derived from plasmids, laboratory viral strains, not on samples from circulating viruses found in ailing patients. The RNA fragments were prepared in Kantor’s lab by Dr. Mia Coetzer, assistant professor of medicine and a co-author on the paper.

    “The next steps are to continue the development of LRA and other methods on patient samples to detect additional mutations and address specific HIV challenges related to mutation detection, such as enormous genomic diversity,” Kantor said, “and work on incorporation of such methods onto a point-of-care device that would satisfy the infrastructure and low-cost needs of resource limited settings.”

    Lei Zhang, a biomedical engineering graduate student in Tripathi’s lab is the lead author on the paper. In addition to Zhang, Coetzer, Tripathi, and Kantor, the paper’s other authors are Jingjing Wang (now at PerkinElmer) and Stephanie Angione (now at Massachusetts General Hospital). within one solution (purple droplet).

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

     
    • serodiscordant canuck 9:06 pm on October 15, 2015 Permalink | Reply

      Great News….It took my partner 2months for his genotype/drug resistance test here in Canada. We are in NS and it is shipped to the other side of the country! Great news…

      Like

  • richardmitnick 6:58 am on October 9, 2015 Permalink | Reply
    Tags: , AIDS, ,   

    From AAAS: “AIDS pioneer finally brings AIDS vaccine to clinic” 

    AAAS

    AAAS

    8 October 2015
    Jon Cohen

    1
    HIV’s gp120 (brown triangle) docking onto a CD4 receptor (grey finger) that studs a white blood cell. Subramaniam Lab/CCR/NCI/NIH. © 2014 Veronica Falconieri.

    Human trials of more than 100 different AIDS vaccines have taken place since researchers proved in 1984 that HIV caused the disease. Robert Gallo, whose U.S. National Cancer Institute laboratory published the four landmark papers in Science that convinced the world of the link between this recently discovered retrovirus and the growing epidemic, has closely monitored—and often sharply critiqued—the AIDS vaccine search since it began. But Gallo, who now runs the Institute of Human Virology (IHV) in Baltimore, Maryland, has always been a spectator—until today.

    Gallo’s team has been developing a vaccine with an unusual method of protection for 15 years and is now launching the first clinical trial of it in collaboration with Profectus BioSciences, a biotech that spun off from IHV recently. Known as a phase I study, the trial expects to enroll 60 people and will simply assess safety and immune responses of the full-length single chain vaccine. “It’s a terrible name,” says Gallo, who is not one to mince words.

    The vaccine contains a version of HIV’s surface protein, gp120, engineered so that it links to a few portions of a protein called the CD4 receptor. When HIV infects cells, gp120 first binds to the CD4 receptor on white blood cells and then “transitions” in such a way that hidden parts of the virus are exposed, allowing it to bind to a second receptor on the immune cells called CCR5. Once bound to both receptors, HIV can enter the white blood cell and establish an infection. The IHV vaccine aims to generate antibodies that bind to HIV’s gp120 when it’s in this transitional state, ultimately blocking attachment to CCR5, aborting the infection process. The development of the vaccine is being led by IHV’s George Lewis, whose team includes Antonio DeVico and Timothy Fouts.

    Gallo, 78, says it has taken a long time to move this vaccine into the clinic because he and his group have done extensive testing in monkeys, faced the typical vaccine challenges of manufacturing a human-grade product, and have had to scramble for funding. “Was anything a lack of courage?” asks Gallo, who frequently asks and answers his own questions. “Sure. We wanted more and more answers before going into people.”

    See the full article here .

    The American Association for the Advancement of Science is an international non-profit organization dedicated to advancing science for the benefit of all people.

    Please help promote STEM in your local schools.
    STEM Icon
    Stem Education Coalition

     
  • richardmitnick 8:47 am on October 5, 2015 Permalink | Reply
    Tags: AIDS, , , , Pegivirus   

    From COSMOS: “The virus that could help stop HIV” 

    Cosmos Magazine bloc

    COSMOS

    5 Oct 2015
    Viviane Richter

    Researchers are starting to unravel the secrets of a virus that not only doesn’t make you sick, but can help you fight off other diseases.

    1
    Macaque monkeys can become infected with the primate version of the pegivirus Credit: egortupikov/gettyimages

    We’ve all heard of friendly bacteria, but a friendly virus? Called the pegivirus, catching it doesn’t make you sick. Instead, it can help the immune system to keep HIV infections in check. Discovered in 1995, scientists do not understand how it works, but that could soon change. Researchers at the Wisconsin National Primate Research Centre recently discovered baboons have their own pegivirus strain, offering a new way to study the oddball virus. Their investigation, published in Science Translational Medicine in September, may inspire new ways to tackle HIV.

    The pegivirus is found in about one in every six people, with infections lasting up to a decade before being cleared from the body. It can be transmitted from mother to child, through contact with an infected person’s blood, or sexually. In the US, where the virus is not included in routine blood bank screens, an estimated 1,000 people receive pegivirus-positive blood or blood products each day.

    While the pegivirus is genetically related to the hepatitis C virus, it doesn’t cause disease. On the contrary, researchers discovered in 2001 that the pegivirus appeared to protect some HIV-positive patients from developing AIDS. An 11-year study of 362 patients found 56% of HIV-positive people who did not carry pegivirus died. But among those patients infected with the pegivirus, the death rate was only 29%.

    How pegivirus thwarts HIV “has really been a bit confusing”, says Stephen Kent, an immunologist at the University of Melbourne. “But if you could mimic that with something that’s more potent – that would be good.”

    So what’s the pegivirus’ secret? “That’s the million-dollar question,” says Adam Bailey, lead author of the new study. Researchers need to study the pegivirus in an animal before it can be answered – one where the virus behaves much as it does in humans, happily cohabiting with its host without causing disease. Macaques failed the test: after being given human pegivirus they quickly cleared the infection. Maybe it was a matter of finding a money-version of the virus? Primates are known to carry viruses closely related to those we carry. For instance many primate species carry a virus closely related to HIV, called Simian Immunodeficiency Virus (SIV)
    .

    So Bailey’s team hunted for a pegivirus that had struck up a long-term relationship with a non-human primate. They found it in 30-year-old samples of baboon blood stashed in a colleague’s freezer. Although that virus was genetically similar to the human strain, when it was injected into macaques it stayed in their blood for up to 200 days without causing harm, long enough for the researchers to study it.

    The researchers euthanised some infected monkeys, analysed their tissues for pegivirus RNA, and found most of the virus nestled in the spleen and bone marrow. These are also the tissues where HIV holes up. Pegivirus appeared to be actively replicating only in bone marrow, since removing the spleen of an infected monkey did not change the blood levels of the virus.

    The fact that pegivirus and HIV are replicating in the same tissues – though not necessarily in the same cells – offers a further a clue to how pegivirus may thwart HIV, says the study’s senior author, David O’Connor.

    When the immune system detects an invading virus, it pumps out more T cells – the infantry of the immune army. Alas that strategy plays right into the enemy’s hands since HIV replicates in and destroys those very cells. More T cells are produced to make up the casualties, giving HIV more cells to exploit. This vicious cycle decimates the immune system.

    2
    Cell infected with HIV. HIV attacks T cells, which are crucial in the body’s immune system. The pegivirus helps the body resist HIV.Credit: THOMAS DEERINCK / NCMIR / getty images

    The researchers found pegivirus seems to slow the recruitment of new T cells from bone marrow. Kent speculates the pegivirus might prompt T cells to make molecules that lock HIV out. For instance the anti-HIV drug Maraviroc acts this way by blocking the CCR5 receptor on T cells.

    The Wisconsin team’s next step will be to co-infect macaques with pegivirus and SIV, the monkey form of HIV, to see how the viruses interact. They hope that once they discover how the pegivirus blocks HIV, they’ll be able to mimic the action with a drug.

    Today’s antiretroviral drugs are good at keeping HIV at bay – it’s estimated they’ve lowered the number of HIV deaths by two-thirds. But as O’Connor says “there’s a lot of space to help people even further”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
  • richardmitnick 10:31 am on August 2, 2015 Permalink | Reply
    Tags: AIDS, ,   

    From Technion: “New Strategy for HIV” 

    Technion bloc

    Technion

    02/08/2015
    No Writer Credit

    In light of the limitations of existing drugs for AIDS:
    Researchers at the Technion Faculty of Biology offer a new strategy to combat the HIV-1 virus

    1
    The illustration appearing on the cover of the Journal of Virology

    The AIDS epidemic continues to take the lives of millions around the world. Despite the resistance of the body cells that are attacked, and despite the use of dedicated drugs, HIV-1 virus manages to survive and reproduce in the living cell and is displaying increasing resistance.

    In light of the partial failure of existing drugs, the strategy of medical research in this field is changing: instead of focusing on the proteins of the virus (and the development of drugs that target them), the new strategy focuses on the interactions of the virus proteins with the host cell.

    This strategy is far more effective, since the virus cannot survive and reproduce without relying on the cellular mechanisms of the host cell. However, the new strategy also has its weaknesses.

    Assistant Prof. Akram Alian of the Technion Faculty of Biology explains that when the virus encounters a barrier on its way into a cell, it looks for ‘detours’ that will enable it to take advantage of the cell nevertheless. Since there is redundancy in the host cell – various mechanisms leading to the same operation – the virus may exploit a self-mutation that could enable it to make use of that detour. “Our hypothesis is that the redundancy in the cellular pathways may represent a survival mechanism that allows the virus to take advantage of a wide variety of similar processes,” says Assistant Prof. Alian. “The virus can use these detours when the favored route is blocked by natural cellular mechanisms or artificial drugs and under other circumstances in which it is better for the virus to circumvent the obstacles of the cellular environment and the various stages of replication.”

    Assistant Prof. Alian and research assistant Dr. Ailie Marx present an abstract of the innovative concept in a paper that was published in the May issue of the Journal of Virology. Janine McCaughey, a visiting student in the lab, illustrates this idea with a drawing of HIV-1 as an octopus whose arms represent takeover paths. The illustration appears on the cover of the issue (http://jvi.asm.org/content/89/12.cover-expansion).

    2
    Assistant Prof. Akram Alian

    An earlier article, published in the journal Cell Structure in October 2014, reviewed a new approach to AIDS research developed by scientists at Assistant Prof. Alian’s laboratory. The researchers conducted a comparison of an important viral protein (integrase) that exists in both HIV-1 and FIV, the AIDS pathogen in cats, and discovered new differences

    that could aid in the understanding and prediction of the development of resistance. With both viruses, the integrase inserts the viral DNA into the DNA of the infected cell, and then replicates itself in a manner that enables it to spread throughout the body.

    “The virus is a kind of Trojan horse, which uses the host’s genome in order to replicate,” explains Assistant Prof. Alian. “Now we are studying this issue in depth and trying to develop this idea of ‘multiple route reproduction of the HIV virus,’ as a new strategy in the treatment of AIDS.”

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Technion Campus

    A science and technology research university, among the world’s top ten,
    dedicated to the creation of knowledge and the development of human capital and leadership,
    for the advancement of the State of Israel and all humanity.

     
  • richardmitnick 3:00 am on March 12, 2015 Permalink | Reply
    Tags: AIDS, , ,   

    From New Scientist: “HIV’s hiding places at last revealed by simple scan” 

    NewScientist

    New Scientist

    09 March 2015
    Clare Wilson

    1
    (Image: medicalrf.com/Getty)

    It’s like using heat cameras to catch criminals on the run, but it finds HIV instead. A novel scanning technique is enabling researchers to pinpoint where in the body HIV is lurking.

    “This could really help with the research for a functional cure,” says Alan Winston of Imperial College London, who was not involved in the study.

    Today’s potent drug treatments can eradicate HIV from the blood, but the virus must survive elsewhere in the body, because it returns when people stop taking these drugs.

    It has been assumed that the virus hides out in immune cells at various “sanctuary sites”, either replicating very slowly or becoming completely dormant. Supporting this, biopsies reveal the virus in sites such as patches of immune tissue in the gut.

    Sanctuary sites

    One strategy to eradicate HIV completely might be to somehow wake up the hiding virus and then kill it. Research into this “kick and kill” strategy is ongoing, but little is known about which sanctuary sites are the most important, what the virus is doing there and whether existing drugs can reach the sites.

    Francois Villinger of Emory University in Atlanta and colleagues wondered if a PET scanning approach, which is also used to show the spread of cancer, could reveal the location of the virus. This idea was prompted by the discovery of an antibody that binds strongly to SIV, the monkey version of HIV.

    To test the idea, the team injected radioactive antibodies into three monkeys with SIV that were being treated with antiviral drugs. PET scanning, which can detect the location of radiation sources within the body, revealed the viral protein, called gp120, in a range of sites including the nose, lungs, gut, genitals and lymph nodes in the armpits and groin. The antibody could not get into the brain, however, which is thought to be another sanctuary site.

    The scans were not detailed enough to reveal which specific cells the virus protein was in, but tests after the monkeys were killed confirmed that the virus was present in the immune cells of the areas identified by the scan.

    Kick and kill

    Although the technique won’t show up a virus that is completely dormant, just being able to see where there is low viral replication is a major advance, says Winston. “It’s the first paper that has allowed us to visualise viral reservoirs.”

    The next step would be to develop antibodies that can recognise the gp120 protein made by the human strain of the virus. Scans made using these could aid researchers working on kick-and-kill strategies, and help investigate the rare cases where people seem to have been cured of HIV.

    This has been claimed for a handful of people who were given bone marrow transplants from donors whose immune cells are resistant to HIV, as well as for an infant who was given antiviral drugs straight after birth.

    Initially after that child – the so-called Mississippi baby – was taken off the drugs, there was no virus detectable in her blood, and her doctor claimed a cure. Unfortunately, after four years the virus returned and she had to restart drug treatment.

    The PET scanning technique could help in such cases, Villinger speculates, by revealing if the virus is present in sanctuary sites.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

     
  • richardmitnick 3:40 pm on February 20, 2015 Permalink | Reply
    Tags: AIDS, , ,   

    From FightAIDS@Home at WCG: “The end of the beginning is near for FightAIDS@Home” 

    WCGLarge
    WCG new
    World Community Grid

    FAAH
    FightAIDS@home

    20 Feb 2015
    The FightAIDS@Home research team

    Summary
    Thanks to the incredible generosity of World Community Grid volunteers, the FightAIDS@Home project team has finished with an important stage of their project. The research team has refocused on analyzing their existing results and preparing for the end of this historic grid computing stage.

    ________________________________________________________________

    FightAIDS@Home has been running on World Community Grid in some form almost since the beginning of World Community Grid itself: our project launched in 2005. Thanks to the enormous and ongoing support of our worldwide community of volunteers, we have expanded the scope of our research and explored new targets and drug candidates that we simply could not imagine at the outset. It hardly seems sufficient to say thank you for donating over 330,000 years of processing time to support our research, but once again, from all of us to all of you: thank you. Clearly we could not do this research without you.

    With your help, we have reached a new milestone: no new AutoDock (AD) or AD Vina docking experiments are currently being generated. Put another way: we’re done creating new work tasks. The AutoDock queue is now empty, and the AD Vina queue has more than a year’s worth of jobs left. Most of our efforts have shifted towards analysis.

    The analysis of the FightAIDS@Home data has several levels of difficulty due to the sheer amounts of data, which are comprised of several structures of any drug target as well as millions of small molecules, resulting in hundreds of millions of data points. We are attempting to use a couple of approaches to mine this data, one of which includes examining amino-acids involved in top-ranked dockings. Another approach is to investigate the atomic coordinates of important interactions (pharmacophore) between the protein and the small molecule that was docked. Figures 1 and 2 (below) illustrate a simple example of inhibitor TL3 (Figure 1) and the predictions of 1 experiment (Figure 2, ~5.5 million dockings on 1 protein structure). Of course, these evaluations must be done with a large set of known inhibitors and across myriad protein structures. Once these methods pass a high level of confidence, molecules will be bought and sent to collaborators to be tested.

    1
    Figure 1. Docked pose of known HIV-1 protease inhibitor TL3 in an HIV-1 protease structure (not shown). Spherical representations (accompanied with dots, orange for TL3, green for a water molecule) represent important locations for protein-ligand interactions that are used to evaluate if a molecule may be a good drug candidate. The green sphere represents the location of an important (“flap”) water molecule often observed in HIV-1 protease co-crystal structures. The 2 orange spheres directly below the green sphere represent two locations of an interaction with significant amino acids (Asp25) of HIV-1 protease.

    3
    Figure 2. Same docked pose of TL3 in HIV-1 protease as Figure 1 with top percentage of interactions from 1 experiment (pink spheres) and several predictions (transparent surfaces) for important protein-ligand interactions. Note that the water molecule (green) and the 2 orange interactions below it are always predicted.

    See the full article here.

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    FightAIDS@Home is a project run by the Olson Laboratory that uses distributed computing to contribute your computer’s idle resources to accelerate research into new drug therapies for HIV, the virus that causes AIDS. FightAIDS@Home made history in September 2000 when it became the first biomedical Internet-based grid computing project. FightAIDS@Home was started with Scott Kurowski, founder of Entropia. People all around the World continue to donate their home computer’s idle cycles to running our AutoDock software on HIV-1 protease inhibitor docking problems. With the generous assistance of IBM, we joined World Community Grid in late 2005, and launched FightAIDS@Home on World Community Grid on 21 November, 2005.

    How do I join the FightAIDS@Home Project?

    All you need to do is download and install the free client software. Once you have done this, your computer is then automatically put to work and you can continue using your computer as usual.

     
c
Compose new post
j
Next post/Next comment
k
Previous post/Previous comment
r
Reply
e
Edit
o
Show/Hide comments
t
Go to top
l
Go to login
h
Show/Hide help
shift + esc
Cancel
Follow

Get every new post delivered to your Inbox.

Join 552 other followers

%d bloggers like this: