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Several minute intermediate stage in virus-cell fusion discovered; opportunity for drug development

a significant amount of time and, in the rare cases in which the pore does not open, it fails to infect the cell at all.

"It's like a space craft docking on a space station," said Young. "If you try to open the inner door before the pressures have equalized, you can tease it open a little bit but it keeps closing on you until there's enough pressure in the airlock to allow it to open all the way."

Melikyan explained, "The pore is an unstable structure at that moment: some pores will open and some won't. It's a crucial point in viral entry because it's critical for the pore to enlarge sufficiently for the genetic material to pass into the host cell."

The researchers are excited by this study because even a brief pause during the process by which a virus invades a cell provides a possible new drug target in the fight against HIV and other similar microbes.

"Our experimental system does pause frequently for hundreds of seconds," said Melikyan. "How this happens in real life is hard to say.

"But our model," he added, "is likely to apply to any virus such as HIV that fuses with the cell membrane and shares the same fusion proteins, so it certainly provides a new target. Also, existing drugs can be re-evaluated to pinpoint at what stage they actually work, to fine-tune their activity."

The experimental set-up for this study was devised by Young and Melikyan last year to investigate viral infection in a manner as close to 'real life' as possible. The researchers filmed the microscopic viruses, which are only 100 nanometers across, by labeling them with fluorescent dyes and recording at one frame every 7 seconds. (For comparison purposes, a human hair is 80,000 nanometers thick.) ASLV is a useful model for several viruses, including Ebola, the 'flu, and measles, as well as HIV.

"This system is especially well suited for these types of studies because the fusion mechanism of this virus can be finely manipulated and moni
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Source:Salk Institute


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