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Re: Interesting news articles about AIDS

Slowing Down Immune System's 'Brakes' May Improve HIV Vaccines

http://www.sciencedaily.com/releases/2010/03/100325113427.htm

"When we removed Treg from blood cells, we found a much stronger immune response to the vaccine, giving us insight into how we can develop more effective HIV vaccines," said Charles R. Rinaldo, Jr., Ph.D.,
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Re: Interesting news articles about AIDS

Controlling HIV: Highly Promising New Compound Developed

http://www.sciencedaily.com/releases/2010/03/100322083850.htm

A compound that can inhibit the transfer of HIV from one cell to another has been developed by researchers at the Institut de Biologie Structurale Jean-Pierre Ebel
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Re: Interesting news articles about AIDS

Scientists Identify How a Novel Class of Antibodies Inhibits HIV Infection

http://www.sciencedaily.com/releases/2010/04/100405091919.htm

these antibodies bind to white blood cells (monocytes), it causes them to secrete substances called chemokines that block HIV from docking with its favorite entry point into a blood cell, the CCR5 receptor. "In other words, they don't go after individual viral particles directly, but instead, indirectly, by creating a chemical roadblock at one of the virus' most commonly used portals."
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Re: Interesting news articles about AIDS

Scientific breakthrough at the IRCM to combat the HIV

http://www.biologynews.net/archives/2010/04/0...m_to_combat_the_hiv1.html

Dr. Cohen's team explains how the Vpu viral protein prevents the expression of Tetherin, a host factor inhibiting HIV-1 release, on the surface of infected cells.
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Dan60
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Re: Interesting news articles about AIDS

Scientists say crack HIV/AIDS puzzle for drugs

British and U.S. researchers said they had grown a crystal that enabled them to see the structure of an enzyme called integrase, which is found in retroviruses like HIV and is a target for some of the newest HIV medicines.



http://www.reuters.com/article/idUSLDE60T0F820100131
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Re: Interesting news articles about AIDS

First Measurement of Energy Released from a Virus During Infection

http://www.sciencedaily.com/releases/2010/02/100205102620.htm

Understanding the energy profile for viral genome release provides information on how to interfere with the process. For example, developing ways to decrease the internal energy in viruses could prevent viruses from ejecting their genome and prevent infection," Evilevitch said
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Re: Interesting news articles about AIDS

Researchers Identify the Source of 'Noise' in HIV

http://www.sciencedaily.com/releases/2010/04/100420132828.htm

"We know that noise in gene-expression can critically influence HIV's entry to proviral latency. These new results point to transcriptional bursting as a major source of the noise" says Dr. Weinberger. "This finding that transcriptional bursting generates an exceptionally noisy HIV promoter, noisier than almost all other measured promoters, supports the theory that latency may be fundamental to the HIV life cycle and that HIV evolved for probabilistic entry into latency."
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mgl_ALPerryman
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biggrin Re: Interesting news articles about AIDS

Hi Papa3,

Thank you for sharing that information about the new discovery of an antiviral lectin from bananas. Antiviral lectins (i.e., sugar-binding proteins that neutralize viruses by binding to the sugars that decorate the ends of the viral spikes) are an extremely promising new approach for the prevention and treatment of enveloped viruses, including HIV.

On a related note, the research I performed during my first postdoctoral fellowship, in Prof. Steve Mayo's lab at Caltech, has led to a US patent application, which describes a strategy that might significantly enhance the anti-HIV potency of the newly-discovered banana lectin:

http://appft.uspto.gov/netacgi/nph-Parser?Sec...=(IN/perryman+AND+IN/mayo

United States Patent Application 20090297516
ENGINEERED LECTINS FOR VIRAL INACTIVATION
by Stephen L. Mayo, Jennifer Keeffe, and Alex L. Perryman


A narrative summary of our invention:
When I was a postdoctoral fellow at Caltech in Pasadena (where Big Bang Theory is supposed to take place), I helped create a compound that will bind to viruses and deactivate them. I did this in a team with Jennifer Keeffe and Professor Steve Mayo (an African-American member of the National Academy of Sciences). The strategy we invented should work against all enveloped viruses, including all strains of HIV, the pox viruses (like Chicken pox or small pox), the Hanta viruses, hepatitis C, herpes, SARS viruses, all strains of influenza (even pandemics that don't exist yet), and Ebola (the scary virus in the movie Outbreak). Enveloped viruses use a devious strategy to hide from the human immune system--they have a coating on their outside that makes them look a bit like a human cell. This cloak is studded with different spikes, which are sort of like the velcro that covers the spherical darts for child-safe dart boards. These spikes are covered in complicated chains of sugars.

Blue-green algae makes a protein called "cyanovirin-N" (sigh-ano-veer-in N). This protein is a "lectin," which means that it binds to sugars. This protein binds to the ends of the sugars that coat the many spikes on these viruses, which makes the viruses less able to infect human cells. I studied many different research articles on this protein cyanovirin-N, from many different fields of science. The papers suggested that the protein is able to fight viruses by binding to those sugars and either forming a cap on them (kind of like putting the opposite piece of velcro over a child's dart or sticking a cork on the point of a conventional dart, so that they won't stick to the dart board anymore), or it works by gumming up the spikes and preventing the changes in shape that they have to perform in order to infect a human cell (sort of like squirting hot glue or solder into an old mechanical clock or putting shackles on the arms and legs of a gymnast). I figured out that if you attach two or three of these proteins together, it should make them much more potent at fighting these enveloped viruses, no matter which of those two ways it uses to disable the viral spikes. By attaching two of these cyanovirin proteins together, we showed that it makes the compound much, much more effective at preventing the fusion of HIV, influenza, or small pox viruses with human cells. It even works much better than the best "neutralizing antibodies," which are what many scientists are studying to try to prevent HIV infections. And this design strategy should work against all of the other enveloped viruses I listed earlier. By attaching two of these lectins together, instead of making it two times more potent, it actually makes the "engineered, multimeric, antiviral lectins" (or "lectimers") 10 to 35 times more effective! After several years of development, refinement, testing, and other things drug companies have to do, these compounds could help prevent and treat many of the worst viruses that plague humanity.


From the patent application:
Abstract
Engineered lectins and methods of using such reagents for both preventing and treating a broad array of viral infections are provided. The lectins of the invention are engineered in two ways, first through the enhancement of the natural mode of action of lectins against viruses through linked multimerization, and second through the creation of a new class of reagents, hereinafter referred to as a "lectibody" or "lectibodies", that engage host immune function in addition to simply binding glycosylated viral proteins via the combination of a lectin and the Fc region of an antibody in order to drive Fc-mediated effector functions including ADCC (antibody-dependent cell-mediated cytotoxicity), increased half-life, complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated phagocytosis (ADCP) in response to a lectin-mediated carbohydrate-binding event.

CONCLUSION
Lectins such as CVN were oligomerized to determine whether an increase in the number of carbohydrate binding sites has an effect on its viral neutralization activity. To create obligate dimers, multiple copies of lectins were covalently linked through flexible polypeptide linkers. Using HIV-1, influenza, and vaccinia as exemplary viral systems, it has been determined that a tandem repeat of two or more lectins increased the efficacy of viral neutralization by up to 35-fold. In addition, multimeric lectin variants show extensive cross-clade reactivity and higher neutralization efficacy for HIV than the most broadly reactive neutralizing antibodies.

Additionally, a novel lectin-Fc chimera, a "lectibody," has been developed, which shows antiviral activity similar to the wild-type lectin, CVN. This variant is dimerized through the Fc region of an antibody and has the additional benefit of incorporating Fc-mediated effector functions, which may be therapeutically advantageous. Initial results on a CVN lectibody indicate that domain swapping has an integral role in the antiviral function as well as in the overall folding and stability of the molecule.



Dr. Jennifer Keeffe and Prof. Steve Mayo at the California Institute of Technology are working on developing this invention further. After performing more experiments, a paper on our new invention will be published. But since the patent application has already been posted on-line, I thought that some of you might appreciate learning more about these antiviral lectins. Progress begets progress. Keep hope alive!

Thank you very much for your interest and for your help,
Dr. Alex L. Perryman
[Apr 22, 2010 7:14:20 PM]   Link   Report threatening or abusive post: please login first  Go to top 
Papa3
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Re: Interesting news articles about AIDS

Glad to be of assistance, Dr. Perryman! hugs Here's another article:

http://www.sciencecodex.com/the_silence_of_th...ses_manipulate_host_cells

Viruses have evolved a broad range of strategies that enable them to evade the immune systems of their hosts. A team of researchers led by LMU virologist Professor Jürgen Haas has been studying a recently discovered mechanism that pathogenic viruses exploit for this purpose, and their latest results could point the way to new antiviral therapies. The mechanism is based on the production of short RNA molecules (microRNAs) by the virus. [...] The sequences of miRNAs are "complementary" to parts of mRNAs, and bind to them to form partially double-stranded structures. This prevents synthesis of the corresponding proteins and may lead to the degradation of the mRNAs. It is estimated that the expression of 20-30% of all human genes is regulated in this way. [...] Viruses too use miRNAs to regulate expression of their genes. But some viral miRNAs do double duty by intervening in the regulation of the host's genes. [...] Haas and his collaborators set out to identify the host mRNAs on which these inhibitory molecules might act. They first isolated the molecular complex that brings the snippets of viral RNA and their targets together. Microarray analysis of the associated host mRNAs then allowed the investigators to identify the corresponding cellular genes affected. "We were able to identify 158 genes in this way" [...] If we could design and deliver therapeutic miRNAs tailored to bind to viral miRNAs, we might be able to defeat the virus by turning its own weapons against it."

Reference: "Systematic Analysis of Viral and Cellular MicroRNA Targets in Cells Latently Infected with Human γ-Herpesviruses by RISC Immunoprecipitation Assay"; Lars Dölken et.al., Cell Host and Microbe online, 22. April 2010 Doi: 10.1016/j.chom.2010.03.008
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Re: Interesting news articles about AIDS

Key Molecular Step to Fighting Off Viruses Identified

http://www.sciencedaily.com/releases/2010/04/100421121454.htm

UT Southwestern Medical Center researchers have determined how a protein that normally latches onto molecules inside cells and marks them for destruction also gives life to the body's immune response against viruses
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