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Advances in cell biology revealed that the plasma membrane is not a homogenous sea of lipid, but consists of various types of microdomains with specific sets of protein and lipid components. One such microdomain is the cholesterol-rich lipid raft. Rafts facilitate various cellular functions, such as signal transduction and protein trafficking, often by providing concentration platforms for promoting protein-protein interactions. A top priority of our research is to fully understand the roles that rafts play throughout the replication cycle of HIV-1 and other retroviruses.
HIV-1 Gag, the major building block of virus particles, has been identified as a raft-associated protein. Moreover, raft disruption severely impairs HIV-1 virus particle production and infectivity of released progeny virions. These findings suggest that rafts play important role(s) in both virus assembly and particle infectivity. We are currently identifying the steps in the assembly/release pathway at which rafts are involved. Future studies will be aimed at determining the molecular mechanisms by which rafts promote virus assembly as well as the nature of the raft subsets involved in infectious virus particle production.
Virus transmission at the interface between two cells is a markedly more efficient mechanism of virus spread than cell-free transmission and likely represents the major mode of transmission for HIV-1 in infected individuals. However, the mechanism of cell-to-cell transmission has not been well studied. Interestingly, we observed that, when a producer cell contacts a target cell, lipid rafts and Gag colocalize at the cell-cell contact interface (see Fig. 1). These results suggest that lipid rafts play a key role in cell-to-cell HIV-1 transmission. The laboratory will further characterize raft-rich contact structures and examine their role(s) in virus spread.
~~~~cited from materials of Ono Lab, University of Michigan Medical School
http://sitemaker.umich.edu/ono.lab/lipid_rafts_and_hiv-1_replication
2008年4月22日 星期二
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