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

To ignite a life-threatening infection in the body, a virus such as HIV invades body cells by first merging, or fusing, with the cell's outer membrane. Once inside the cell, the invading microbe's genetic material takes over, turning the 'host' cell into a factory to produce more copies of the virus, which then spill out to invade other cells in the body.

Scientists had assumed that once a virus begins fusing with a cell's membrane, infection of the host cell was inevitable. Thus, antiviral drug development has largely focused on preventing events that happen either before or after this step.

However, a multi-institutional team of researchers is reporting that it has detected an intermediate stage between the virus' merger with the cell membrane and the microbe's delivery of its genetic contents into the cell, when the fate of the host cell still hangs in the balance.

This intermediate stage, which can last several minutes, may represent a window of opportunity for drug development. The remarkable findings, captured on video, were published by the Proceedings of the National Academy of Sciences online on June 3. Biophysicist Gregory Melikyan of Rush University Medical Center in Chicago and microbiologist John Young of the Salk Institute for Biological Studies filmed individual viruses fusing with a host cell membrane. Avian sarcoma and leukosis virus (ASLV), a virus that is in the same class as HIV, was used in the study.

The researchers discovered that once the virus fuses with the host cell membrane the hole, or pore, through which the virus unloads its deadly genetic cargo into the host cell does not open up right away; instead, a small pore can persist for several minutes before adopting its final size, or (in rare cases) closing permanently.

This 'intermediate stage,' as the scientists describe this time interval, was not known to exist for virus-cell fusion events. The net effect is that the invading virus is held up for
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Source:Salk Institute


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