Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency

Sariah J. Allen, Antje Rhode-Kurnow, Kevin R. Mott, Xianzhi Jiang, Dale Carpenter, J. Ignacio Rodriguez-Barbosa, Clinton J Jones, Steven L. Wechsler, Carl F. Ware, Homayon Ghiasi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1961-1971
Number of pages11
JournalJournal of virology
Volume88
Issue number4
DOIs
StatePublished - Feb 1 2014

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Receptors, Tumor Necrosis Factor, Member 14
Human herpesvirus 1
cell viability
immune response
herpes simplex
viruses
surface proteins
cell-mediated immunity
promoter regions
cells
Virus Latency
mice
Human Herpesvirus 1
genes
Cell Survival
herpes simplex virus-1 latency associated transcript
Virus Attachment
Small Untranslated RNA
Viral Genes
Simplexvirus

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Allen, S. J., Rhode-Kurnow, A., Mott, K. R., Jiang, X., Carpenter, D., Rodriguez-Barbosa, J. I., ... Ghiasi, H. (2014). Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency. Journal of virology, 88(4), 1961-1971. https://doi.org/10.1128/JVI.02467-13

Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency. / Allen, Sariah J.; Rhode-Kurnow, Antje; Mott, Kevin R.; Jiang, Xianzhi; Carpenter, Dale; Rodriguez-Barbosa, J. Ignacio; Jones, Clinton J; Wechsler, Steven L.; Ware, Carl F.; Ghiasi, Homayon.

In: Journal of virology, Vol. 88, No. 4, 01.02.2014, p. 1961-1971.

Research output: Contribution to journalArticle

Allen, SJ, Rhode-Kurnow, A, Mott, KR, Jiang, X, Carpenter, D, Rodriguez-Barbosa, JI, Jones, CJ, Wechsler, SL, Ware, CF & Ghiasi, H 2014, 'Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency', Journal of virology, vol. 88, no. 4, pp. 1961-1971. https://doi.org/10.1128/JVI.02467-13
Allen, Sariah J. ; Rhode-Kurnow, Antje ; Mott, Kevin R. ; Jiang, Xianzhi ; Carpenter, Dale ; Rodriguez-Barbosa, J. Ignacio ; Jones, Clinton J ; Wechsler, Steven L. ; Ware, Carl F. ; Ghiasi, Homayon. / Interactions between herpesvirus entry mediator (TNFRSF14) and latency-associated transcript during herpes simplex virus 1 latency. In: Journal of virology. 2014 ; Vol. 88, No. 4. pp. 1961-1971.
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