title: Inhibition of integrin α6 expression by cell-free varicella-zoster virus.
abstract: Varicella-zoster virus (VZV) causes chickenpox and shingles. VZV is released from infected cells during natural infection, but remains highly cell-associated during experimental infection, and so most studies have utilized cell-associated infection models. We examined the impact of cell-free VZV infection of primary human foreskin fibroblasts (HFFs) on the receptor integrin α6 (ITGA6). qPCR and flow cytometry demonstrated that both cell-free VZV and cell-free UV-inactivated VZV downregulated transcription and cell-surface protein expression of ITGA6. To establish whether ITGA6 altered VZV infection, VZV transcripts and nuclear DNA levels were measured in HFFs treated with ITGA6 blocking antibody before infection. ITGA6 blocking did not impair virus entry but did negatively impact VZV transcription, and this effect was virus specific as transcription of the related herpes simplex virus type 1 was not similarly inhibited. This study identifies modulation of ITGA6 during cell-free VZV infection, and provides the first evidence linking ITGA6 with post-entry productive VZV gene expression.
authors.affiliation: Centre for Virus Research, Westmead Millennium Institute, NSW, Australia.
authors.forename: Joshua B
authors.initials: JB
authors.lastname: Bowles
authors.affiliation: Infectious Diseases and Immunology, University of Sydney, NSW, Australia.|Centre for Virus Research, Westmead Millennium Institute, NSW, Australia.
authors.forename: Megan
authors.initials: M
authors.lastname: Steain
authors.affiliation: Infectious Diseases and Immunology, University of Sydney, NSW, Australia.|Centre for Virus Research, Westmead Millennium Institute, NSW, Australia.
authors.forename: Barry
authors.initials: B
authors.lastname: Slobedman
authors.affiliation: Infectious Diseases and Immunology, University of Sydney, NSW, Australia.|Centre for Virus Research, Westmead Millennium Institute, NSW, Australia.
authors.forename: Allison
authors.initials: A
authors.lastname: Abendroth
mesh_terms: D000914:Antibodies, Viral; D002478:Cells, Cultured; D004279:DNA, Viral; D005347:Fibroblasts / Q000378:metabolism* / Q000821:virology*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000502:physiology*; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D039503:Integrin alpha6