title: Permissive and restricted virus infection of murine embryonic stem cells.
abstract: Recent RNA interference (RNAi) studies have identified many host proteins that modulate virus infection, but small interfering RNA 'off-target' effects and the use of transformed cell lines limit their conclusiveness. As murine embryonic stem (mES) cells can be genetically modified and resources exist where many and eventually all known mouse genes are insertionally inactivated, it was reasoned that mES cells would provide a useful alternative to RNAi screens. Beyond allowing investigation of host-pathogen interactions in vitro, mES cells have the potential to differentiate into other primary cell types, as well as being used to generate knockout mice for in vivo studies. However, mES cells are poorly characterized for virus infection. To investigate whether ES cells can be used to explore host-virus interactions, this study characterized the responses of mES cells following infection by herpes simplex virus type 1 (HSV-1) and influenza A virus. HSV-1 replicated lytically in mES cells, although mES cells were less permissive than most other cell types tested. Influenza virus was able to enter mES cells and express some viral proteins, but the replication cycle was incomplete and no infectious virus was produced. Knockdown of the host protein AHCYL1 in mES cells reduced HSV-1 replication, showing the potential for using mES cells to study host-virus interactions. Transcriptional profiling, however, indicated the lack of an efficient innate immune response in these cells. mES cells may thus be useful to identify host proteins that play a role in virus replication, but they are not suitable to determine factors that are involved in innate host defence.
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors: Rachael
authors: R
authors: Wash
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors: Sabrina
authors: S
authors: Calabressi
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors: Stephanie
authors: S
authors: Franz
authors: Division of Pathway Medicine, The University of Edinburgh, Old College, South Bridge, Edinburgh, EH8 9YL, UK.
authors: Samantha J
authors: SJ
authors: Griffiths
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors: David
authors: D
authors: Goulding
authors: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors: E-Pien
authors: EP
authors: Tan
authors: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
authors: Helen
authors: H
authors: Wise
authors: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
authors: Paul
authors: P
authors: Digard
authors: Division of Pathway Medicine, The University of Edinburgh, Old College, South Bridge, Edinburgh, EH8 9YL, UK.
authors: Jürgen
authors: J
authors: Haas
authors: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
authors: Stacey
authors: S
authors: Efstathiou
authors: UCL/MRC Centre for Medical Molecular Virology, Department of Infection, University College London, London WC1E 6BT, UK.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors: Paul
authors: P
authors: Kellam
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004261:DNA Replication / Q000235:genetics; D004285:Dogs; D053595:Embryonic Stem Cells / Q000378:metabolism / Q000502:physiology* / Q000821:virology*; D006367:HeLa Cells; D006561:Herpes Simplex / Q000235:genetics / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics*
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins