Báo cáo y học: "Tetherin restricts direct cell-to-cell infection of HIV-1"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Tetherin restricts direct cell-to-cell infection of HIV-1. | Kuhl et al. Retrovirology 2010 7 115 http content 7 1 115 RETR0VIR0L0GY RESEARCH Open Access Tetherin restricts direct cell-to-cell infection of HIV-1 1 13 1 Bjorn D Kuhl Richard D Sloan Daniel A Donahue Tamara Bar-Magen Chen Liang Mark A Wainberg Abstract Background Tetherin BST-2 CD317 is an interferon IFN -inducible factor of the innate immune system recently shown to exert antiviral activity against HIV-1 and other enveloped viruses by tethering nascent viral particles to the cell surface thereby inhibiting viral release. In HIV-1 infection the viral protein U Vpu counteracts this antiviral action by down-modulating tetherin from the cell surface. Viral dissemination between T-cells can occur via cell-free transmission or the more efficient direct cell-to-cell route through lipid raft-rich virological synapses to which tetherin localizes. Results We established a flow cytometry-based co-culture assay to distinguish viral transfer from viral transmission and investigated the influence of tetherin on cell-to-cell spread of HIV-1. Sup-T1 cells inducible for tetherin expression were used to examine the impact of effector and target cell tetherin expression on virus transfer and transmission. Using this assay we showed that tetherin inhibits direct cell-to-cell virus transfer and transmission. Viral Vpu promoted viral transmission from tetherin-expressing cells by down-modulating tetherin from the effector cell surface. Further we showed that tetherin on the target cell promotes viral transfer and transmission. Viral infectivity in itself was not affected by tetherin. Conclusion In addition to inhibiting viral release tetherin also inhibits direct cell-to-cell spread. Viral protein Vpu counteracts this restriction outweighing its possible cost of fitness in cell-to-cell transmission. The differential role of tetherin in effector and target cells suggest a role for tetherin in cell-cell contacts and virological synapses. .

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