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Study provides new details of 'the birth of a virus'

e cell (see accompanying illustration). Thousands of newborn viruses now cling to the outside of the membrane, waiting for one final step to cut them loose and send them on their way to other cells.

Ten years ago, Gttlinger and his colleagues at Dana-Farber discovered that a strain of HIV that lacks the late domain was unable to break free of the membrane - remaining attached and posing no threat to the rest of the body. The new study fills in some of the gaps in scientists' understanding of how the late domain functions and how it serves as a passport through the cell's skin.

Small as the late domain is within Gag, the domain's essential core - the part that enables it to function - often consists of only a handful of molecules, primarily amino acids known as prolines. Researchers have found that all retroviruses, not just HIV, have late domains, as do a variety of other viruses.

"These findings suggest that many viruses use the same or similar mechanisms to cut themselves loose from the cell membrane," Gttlinger says. "The discovery of the proline-rich sections of the late domain enabled us to focus on precisely these areas in studying how the domain functions." The researchers hypothesized that the late domain serves as a target for cell proteins that help the virus break free from the cell membrane. Their research shows this to be precisely the case.

The possibility of interrupting the budding process marks the significance of this recently published research. Working independently, scientists at Dana-Farber Cancer Institute, Penn State's College of Medicine and The National Institute of Allergies and Infectious Diseases (NIAID) of the National Institutes of Health, published complementary papers on the role of the cellular ubiquitination machinery in late steps of retrovirus budding.

The data show the functional connection between ubiquitin and Gag (Penn State), the recruitment of ubiquitin ligase, which encourages the
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Contact: Todd Ringler
todd_ringler@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
20-Nov-2000


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