title: Phosphoinositide 3 kinase signalling may affect multiple steps during herpes simplex virus type-1 entry.
abstract: 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 β- and γ-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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D002459:Cell Fusion; D002478:Cells, Cultured; D002867:Chromones / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D008856:Microscopy, Fluorescence; D009025:Morpholines / Q000378:metabolism; D015388:Organelles / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction; D053586:Virus Internalization
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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