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Author Topic: FEZ-1 protein in brain cells blocks HIV infection  (Read 1691 times)

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Offline Cosmicdancer

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FEZ-1 protein in brain cells blocks HIV infection
« on: July 29, 2009, 08:48:26 PM »
This is another avenue for drug development, although it's in the basic science phase at this point.  Still, the article points out that it creates potential for another new class of drugs or a gene therapy.  I'm glad to see that Sangamo Biosciences seems to think this has potential.

http://www.newscientist.com/article/dn17523-brain-cells-have-natural-resistance-to-hiv.html
 
Brain cells have natural resistance to HIV
28 July 2009 by Andy Coghlan

Neurons can protect themselves against infection with HIV, new research has demonstrated. They owe their hardiness to a protein called FEZ-1, made uniquely by neurons, and which appears to lock out the virus.

The finding raises the possibility of new treatments to thwart HIV by using gene therapy or drugs to activate production of the same protein in cells other than neurons especially the white blood cells most vulnerable to infection.

Mojgan Naghavi of University College Dublin, Ireland, along with her colleagues Juliane Haedicke and Craig Brown, established the protective effects of FEZ-1 by blocking production of the protein in human neurons.

When they did this, the neurons became vulnerable to infection. Likewise, they successfully blocked the usual infections in other types of brain cells, such as microglia, by engineering them to manufacture FEZ-1.

Transport blocker?
Next, the researchers hope to see if they can block HIV infection in white blood cells by genetically engineering them to produce FEZ-1. They also hope to find out more about how FEZ-1 blocks HIV.

"We know FEZ-1 blocks infection, but we need to find the basic mechanism," says Naghavi.

Standing for fasciculation and elongation protein zeta-1, FEZ-1 is known to bind to molecular "motors" that help to transport proteins within cells along internal tramlines known as microtubules. Naghavi says it may be that FEZ-1 gets in the way, blocking transport of viral proteins into the nucleus where they would multiply.

Second weapon
The only other established source of natural protection against infection is in people who can't make CCR5, a surface protein that HIV uses to gain entry to cells.

Drugs already exist to block CCR5, and other teams are testing gene therapies to restock patients' blood with cells engineered to not produce CCR5.

Sangamo Biosciences of Richmond, California, began such a trial earlier this year, using a method to disable the CCR5 gene in blood samples before returning them to patients. The company says it is theoretically possible to activate the FEZ-1 gene in cells vulnerable to HIV infection.

Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0900502106)

Summer, 2007 - &$#@?
November, 2007 - Tested poz, 300,000 vl, 560 cd4
Feb, 2008 - 57,000 vl, 520 cd4, started Atripla
June, 2008 - undetectable, 612 cd4
January, 2009 - undetectable, 670 cd4
May, 2009 - undetectable, 593 cd4
Sept, 2009 - 83 vl, 763 cd4, 34%
Dec, 2009 - undetectable, 889 cd4, 32%
April, 2010 - undetectable, 860 cd4, 31%
October, 2010 - undetectable, 800 cd4, 38%
April, 2011 - undetectable, t-cell test not done
October, 2011 - undetectable
April, 2012 - undetectable, 850 cd4, 39%
November, 2012 - undetectable, 901 cd4, 41%
April, 2013 - undetectable, 846 cd4, 36%
October, 2013 - undetectable
May, 2014 - undetectable, 784 cd4, 48%

 


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