Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument protein

Mathieu Iampietro, Guillaume Morissette, Annie Gravel, Louis Flamand

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen causing lifelong infections in approximately 95% of humans worldwide. To persist within its host, HHV-6B has developed several immune evasion mechanisms, such as latency, during which minimal proteins are expressed, and the ability to disturb innate and adaptive immune responses. The primary cellular targets of HHV-6B are CD4+ T cells. Previous studies by Flamand et al. (L. Flamand, J. Gosselin, I. Stefanescu, D. Ablashi, and J. Menezes, Blood 85:1263-1271, 1995) reported on the capacity of HHV-6A as well as UV-irradiated HHV-6A to inhibit interleukin-2 (IL-2) synthesis in CD4+ lymphocytes, suggesting that viral structural components could be responsible for this effect. In the present study, we identified the HHV-6B U54 tegument protein (U54) as being capable of inhibiting IL-2 expression. U54 binds the calcineurin (CaN) phosphatase enzyme, causing improper dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T cells) proteins, resulting in suboptimal IL-2 gene transcription. The U54 GISIT motif (amino acids 293 to 297), analogous to the NFAT PXIXIT motif, contributed to the inhibition of NFAT activation.

Original languageEnglish (US)
Pages (from-to)12452-12463
Number of pages12
JournalJournal of Virology
Volume88
Issue number21
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Human Herpesvirus 6
interleukin-2
Interleukin-2
NFATC Transcription Factors
Gene Expression
gene expression
T-lymphocytes
Proteins
proteins
amino acid motifs
immune evasion
dephosphorylation
Immune Evasion
Viral Structures
Amino Acid Motifs
Adaptive Immunity
Innate Immunity
lymphocytes
transcription (genetics)
synthesis

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Medicine(all)

Cite this

Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument protein. / Iampietro, Mathieu; Morissette, Guillaume; Gravel, Annie; Flamand, Louis.

In: Journal of Virology, Vol. 88, No. 21, 2014, p. 12452-12463.

Research output: Contribution to journalArticle

Iampietro, M, Morissette, G, Gravel, A & Flamand, L 2014, 'Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument protein', Journal of Virology, vol. 88, no. 21, pp. 12452-12463. https://doi.org/10.1128/JVI.02030-14
Iampietro, Mathieu ; Morissette, Guillaume ; Gravel, Annie ; Flamand, Louis. / Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument protein. In: Journal of Virology. 2014 ; Vol. 88, No. 21. pp. 12452-12463.
@article{3bdd9fac7f3b4cff8859220c51eae3a8,
title = "Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument protein",
abstract = "Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen causing lifelong infections in approximately 95{\%} of humans worldwide. To persist within its host, HHV-6B has developed several immune evasion mechanisms, such as latency, during which minimal proteins are expressed, and the ability to disturb innate and adaptive immune responses. The primary cellular targets of HHV-6B are CD4+ T cells. Previous studies by Flamand et al. (L. Flamand, J. Gosselin, I. Stefanescu, D. Ablashi, and J. Menezes, Blood 85:1263-1271, 1995) reported on the capacity of HHV-6A as well as UV-irradiated HHV-6A to inhibit interleukin-2 (IL-2) synthesis in CD4+ lymphocytes, suggesting that viral structural components could be responsible for this effect. In the present study, we identified the HHV-6B U54 tegument protein (U54) as being capable of inhibiting IL-2 expression. U54 binds the calcineurin (CaN) phosphatase enzyme, causing improper dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T cells) proteins, resulting in suboptimal IL-2 gene transcription. The U54 GISIT motif (amino acids 293 to 297), analogous to the NFAT PXIXIT motif, contributed to the inhibition of NFAT activation.",
author = "Mathieu Iampietro and Guillaume Morissette and Annie Gravel and Louis Flamand",
year = "2014",
doi = "10.1128/JVI.02030-14",
language = "English (US)",
volume = "88",
pages = "12452--12463",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "21",

}

TY - JOUR

T1 - Inhibition of interleukin-2 gene expression by human herpesvirus 6B U54 tegument protein

AU - Iampietro, Mathieu

AU - Morissette, Guillaume

AU - Gravel, Annie

AU - Flamand, Louis

PY - 2014

Y1 - 2014

N2 - Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen causing lifelong infections in approximately 95% of humans worldwide. To persist within its host, HHV-6B has developed several immune evasion mechanisms, such as latency, during which minimal proteins are expressed, and the ability to disturb innate and adaptive immune responses. The primary cellular targets of HHV-6B are CD4+ T cells. Previous studies by Flamand et al. (L. Flamand, J. Gosselin, I. Stefanescu, D. Ablashi, and J. Menezes, Blood 85:1263-1271, 1995) reported on the capacity of HHV-6A as well as UV-irradiated HHV-6A to inhibit interleukin-2 (IL-2) synthesis in CD4+ lymphocytes, suggesting that viral structural components could be responsible for this effect. In the present study, we identified the HHV-6B U54 tegument protein (U54) as being capable of inhibiting IL-2 expression. U54 binds the calcineurin (CaN) phosphatase enzyme, causing improper dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T cells) proteins, resulting in suboptimal IL-2 gene transcription. The U54 GISIT motif (amino acids 293 to 297), analogous to the NFAT PXIXIT motif, contributed to the inhibition of NFAT activation.

AB - Human herpesvirus 6B (HHV-6B) is a ubiquitous pathogen causing lifelong infections in approximately 95% of humans worldwide. To persist within its host, HHV-6B has developed several immune evasion mechanisms, such as latency, during which minimal proteins are expressed, and the ability to disturb innate and adaptive immune responses. The primary cellular targets of HHV-6B are CD4+ T cells. Previous studies by Flamand et al. (L. Flamand, J. Gosselin, I. Stefanescu, D. Ablashi, and J. Menezes, Blood 85:1263-1271, 1995) reported on the capacity of HHV-6A as well as UV-irradiated HHV-6A to inhibit interleukin-2 (IL-2) synthesis in CD4+ lymphocytes, suggesting that viral structural components could be responsible for this effect. In the present study, we identified the HHV-6B U54 tegument protein (U54) as being capable of inhibiting IL-2 expression. U54 binds the calcineurin (CaN) phosphatase enzyme, causing improper dephosphorylation and nuclear translocation of NFAT (nuclear factor of activated T cells) proteins, resulting in suboptimal IL-2 gene transcription. The U54 GISIT motif (amino acids 293 to 297), analogous to the NFAT PXIXIT motif, contributed to the inhibition of NFAT activation.

UR - http://www.scopus.com/inward/record.url?scp=84907977336&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907977336&partnerID=8YFLogxK

U2 - 10.1128/JVI.02030-14

DO - 10.1128/JVI.02030-14

M3 - Article

VL - 88

SP - 12452

EP - 12463

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 21

ER -