NEURONS can protect themselves against infection from HIV. They owe their hardiness to a protein called FEZ-1, made uniquely by neurons, which appears to lock out the virus.
The hope now is to produce treatments to thwart HIV by using gene therapy or drugs to activate production of FEZ-1 in cells other than neurons, especially the white blood cells most vulnerable to infection by the virus.
鈥淲e know FEZ-1 blocks infection, but we need to find the basic mechanism,鈥� says of University College Dublin in Ireland, head of the team reporting the breakthrough in Proceedings of the National Academy of Sciences (). Once scientists understand how FEZ-1 blocks infection, it may be possible to produce drugs that do the same job.
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Naghavi and her colleagues Juliane Haedicke and Craig Brown established the protective effects of FEZ-1 by blocking the gene that makes it in human neurons. This made the neurons vulnerable to infection. Likewise, the team blocked infection that would normally occur in other types of brain cells, such as microglia, by genetically engineering them to manufacture FEZ-1. They now hope to achieve the same thing in macrophages, a type of white blood cell.
FEZ-1 is known to bind to molecular 鈥渕otors鈥� that help cells transport proteins along internal tramlines known as microtubules. Naghavi says it may be that FEZ-1 jams the motors, blocking transport of viral proteins into the nucleus, where they multiply.
The only other known natural protection against HIV infection is the rare inability to make CCR5, a surface protein that HIV grips onto to gain entry to cells. Drugs exist to block CCR5, and researchers are testing gene therapies to restock patients鈥� blood with cells engineered so they no longer make it.