title: Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency.
abstract: Herpesvirus entry mediator (HVEM) is one of several cell surface proteins herpes simplex virus (HSV) uses for attachment/entry. HVEM regulates cellular immune responses and can also increase cell survival. Interestingly, latency-associated transcript (LAT), the only viral gene consistently expressed during neuronal latency, enhances latency and reactivation by promoting cell survival and by helping the virus evade the host immune response. However, the mechanisms of these LAT activities are not well understood. We show here for the first time that one mechanism by which LAT enhances latency and reactivation appears to be by upregulating HVEM expression. HSV-1 latency/reactivation was significantly reduced in Hvem(-/-) mice, indicating that HVEM plays a significant role in HSV-1 latency/reactivation. Furthermore, LAT upregulated HVEM expression during latency in vivo and also when expressed in vitro in the absence of other viral factors. This study suggests a mechanism whereby LAT upregulates HVEM expression potentially through binding of two LAT small noncoding RNAs to the HVEM promoter and that the increased HVEM then leads to downregulation of immune responses in the latent microenvironment and increased survival of latently infected cells. Thus, one of the mechanisms by which LAT enhances latency/reactivation appears to be through increasing expression of HVEM.
authors.affiliation: Center for Neurobiology and Vaccine Development, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Sariah J
authors.initials: SJ
authors.lastname: Allen
authors.forename: Antje
authors.initials: A
authors.lastname: Rhode-Kurnow
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Mott
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Jiang
authors.forename: Dale
authors.initials: D
authors.lastname: Carpenter
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Rodriguez-Barbosa
authors.forename: Clinton
authors.initials: C
authors.lastname: Jones
authors.forename: Steven L
authors.initials: SL
authors.lastname: Wechsler
authors.forename: Carl F
authors.initials: CF
authors.lastname: Ware
authors.forename: Homayon
authors.initials: H
authors.lastname: Ghiasi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000502:physiology*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D057131:Immune Evasion / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017735:Virus Latency / Q000502:physiology*
chemical_list: D017931:DNA Primers; D035683:MicroRNAs; D053240:Receptors, Tumor Necrosis Factor, Member 14; C506029:Tnfrsf14 protein, mouse; C477253:latency associated transcript, herpes simplex virus-1