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Does the Kaposi sarcoma (KS) herpesvirus (KSHV) replicate in lymphatic endothelial cells (LECs) or blood vascular endothelial cells (BECs)? Two groups have come up with a surprising answer to this question: neither. Instead the oncogenic virus modifies both of the two cell types to an intermediate state that better suits the virus' replicative needs.+ }# H( \- r+ N% Z
Y0 K- `# H1 NKS has always been known as a tumor of the endothelial system based on the reddish, bruised appearance of KS lesions. A handful of lymphatic markers are found on KSHV-infected cells, but two new studies by Hsei-Wei Wang, Chris Boshoff (University College London, UK), and colleagues and Young-Kwon Hong, Michael Detmar (Harvard Medical School, Boston, MA), and colleagues present the first comprehensive view of what these cells express.9 U4 e) t$ z2 J/ U" N( C4 B- S
' Q# J" v8 p& K, | g6 F- w) VThe Boston group finds that BECs infected with KSHV induce 70% of known lymphatic lineage-specific genes. Part of this effect is mediated by a lymphatic master regulator PROX1, earlier characterized by Hong, but other factors must also be necessary. The London group independently finds that infected BECs become more like LECs, and further finds that infected LECs become more like BECs. The final result is an intermediate cellular state that is neither BEC nor LEC, but presumably suits the virus just fine.
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; m( ]/ K/ r/ d5 a8 b; i6 hThe virus in humans may infect endothelial precursors rather than mature, differentiated cells, but it remains unclear whether such an infection would drive precursors down a particular differentiation pathway. What is clear, says Boshoff, is that the virus "can exploit lymphatic differentiation to complete its cycle." He suggests that transcription factors used to determine the lymphatic phenotype are probably also used by the virus to aid its reproduction.
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References:
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Hong, Y.-K., et al. 2004. Nat. Genet. 36:683–685.
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+ M, s0 a4 m% v1 F( v1 rWang, H.-W., et al. 2004. Nat. Genet. 36:687–693.(Infected LECs and BECs converge toward a) |
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发表于 2009-3-6 08:14
发表于 2015-5-28 13:10
