期刊
JOURNAL OF GENERAL VIROLOGY
卷 91, 期 -, 页码 3002-3009出版社
SOC GENERAL MICROBIOLOGY
DOI: 10.1099/vir.0.024166-0
关键词
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资金
- NIH [AI057860, AI081869, EY01792]
- Research to Prevent Blindness (RPB)
- WUHS [N12587]
Early interactions of herpes simplex virus type-1 (HSV-1) with cells lead to cytoskeletal changes facilitating filopodia formation and membrane fusion Here, we demonstrate that phosphoinositide 3 kinase (PI3K) signalling may affect multiple steps during HSV-1 entry An inhibitor of PI3K (LY294002) blocked HSV-1 entry and the blockage was cell-type- and gD receptor-independent Entry inhibition was also observed with primary cultures of the human corneal fibroblasts and unrelated beta- and gamma-herpesviruses Immunofluorescence analysis demonstrated that LY294002 negatively affected HSV-1-induced filopodia formation Similar effects of the inhibitor were seen on HSV-1 glycoprotein-induced cell-to-cell fusion Cells expressing HSV-1 glycoproteins (gB gD gH and gL) showed significantly less fusion with target cells in the presence of the inhibitor Expression of a dominant-negative PI3K mutant negatively affected both entry and fusion We also show that inhibition of PI3K signalling also affected RhoA activation required for HSV-1 entry into certain cell types
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