title: Expression of the herpes simplex virus type 1 latency-associated transcripts does not influence latency establishment of virus mutants deficient for neuronal replication.
abstract: Herpes simplex virus type 1 establishes latency within neurons of the trigeminal ganglion. During latency, viral gene expression is largely restricted to the latency-associated transcripts (LATs), which, whilst not essential for any aspect of latency, function to suppress lytic gene expression and enhance the survival of virus-infected neurons. The latent cell population comprises primary-order neurons infected directly from peripheral tissues and cells infected following further virus spread within the ganglion. In order to assess the role of LAT expression on latency establishment within first-order neurons, we infected ROSA26R reporter mice with Cre recombinase-expressing recombinant viruses harbouring deletion of the thymidine kinase lytic gene and/or the core LAT promoter. We found that LAT expression did not impact on latency establishment in viruses unable to replicate in neurons, and under these conditions, it was not required for the survival of neurons between 3 and 31 days post-infection.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Nicoll
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: S
authors.initials: S
authors.lastname: Efstathiou
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000821:virology*; D013937:Thymidine Kinase / Q000235:genetics; D012668:Trigeminal Ganglion / Q000821:virology; D017735:Virus Latency / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D035683:MicroRNAs; C477253:latency associated transcript, herpes simplex virus-1; D013937:Thymidine Kinase
references.citation: EMBO J. 1989 Feb;8(2):505-11
references.pmid: 2542019
references.citation: J Virol. 1997 Jun;71(6):4199-208
references.pmid: 9151806
references.citation: J Gen Virol. 1989 Apr;70 ( Pt 4):869-79
references.pmid: 2543763
references.citation: J Virol. 2006 Jan;80(1):38-50
references.pmid: 16352529
references.citation: J Virol. 2012 Aug;86(16):8848-58
references.pmid: 22696655
references.citation: Science. 2000 Feb 25;287(5457):1500-3
references.pmid: 10688801
references.citation: J Virol. 1997 Aug;71(8):5878-84
references.pmid: 9223477
references.citation: J Virol. 2010 May;84(9):4659-72
references.pmid: 20181707
references.citation: J Virol. 1989 Jul;63(7):2893-900
references.pmid: 2542601
references.citation: J Gen Virol. 2011 Nov;92(Pt 11):2575-2585
references.pmid: 21752961
references.citation: J Neurovirol. 2011 Dec;17(6):552-8
references.pmid: 22207584
references.citation: J Virol. 2009 Aug;83(16):8182-90
references.pmid: 19515781
references.citation: Nature. 2008 Aug 7;454(7205):780-3
references.pmid: 18596690
references.citation: J Virol. 2005 Jul;79(14):9019-25
references.pmid: 15994795
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16055-9
references.pmid: 16247011
references.citation: J Virol. 1997 Apr;71(4):3197-207
references.pmid: 9060683
references.citation: J Virol. 1994 Dec;68(12):8045-55
references.pmid: 7966594
references.citation: J Virol. 1997 Aug;71(8):5885-93
references.pmid: 9223478
references.citation: Virology. 1988 Sep;166(1):254-7
references.pmid: 2842950
references.citation: J Virol. 1987 Dec;61(12):3820-6
references.pmid: 2824816
references.citation: J Gen Virol. 1988 Jul;69 ( Pt 7):1531-74
references.pmid: 2839594
references.citation: Immunol Cell Biol. 2008 Nov-Dec;86(8):666-75
references.pmid: 18607387
references.citation: J Virol. 1997 Jul;71(7):5432-40
references.pmid: 9188615
references.citation: Science. 1987 Feb 27;235(4792):1056-9
references.pmid: 2434993
references.citation: J Virol. 2000 Feb;74(4):1885-91
references.pmid: 10644361
references.citation: J Virol. 1998 Aug;72(8):6888-92
references.pmid: 9658140
references.citation: Proc Natl Acad Sci U S A. 1989 Jun;86(12):4736-40
references.pmid: 2543985
references.citation: J Virol. 2001 Jul;75(14):6660-75
references.pmid: 11413333
references.citation: J Virol. 2000 Jan;74(2):965-74
references.pmid: 10623759
references.citation: J Gen Virol. 2008 Dec;89(Pt 12):2965-2974
references.pmid: 19008381
references.citation: J Virol. 1998 Jun;72(6):5067-75
references.pmid: 9573277
references.citation: Virology. 1990 Jan;174(1):117-25
references.pmid: 2152989