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Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus.

Publication ,  Journal Article
Linnstaedt, SD; Gottwein, E; Skalsky, RL; Luftig, MA; Cullen, BR
Published in: J Virol
November 2010

Infection of resting primary human B cells by Epstein-Barr virus (EBV) results in their transformation into indefinitely proliferating lymphoblastoid cell lines (LCLs). LCL formation serves as a model for lymphomagenesis, and LCLs are phenotypically similar to EBV-positive diffuse large B-cell lymphomas (DLBCLs), which represent a common AIDS-associated malignancy. B-cell infection by EBV induces the expression of several cellular microRNAs (miRNAs), most notably miR-155, which is overexpressed in many tumors and can induce B-cell lymphomas when overexpressed in animals. Here, we demonstrate that miR-155 is the most highly expressed miRNA in LCLs and that the selective inhibition of miR-155 function specifically inhibits the growth of both LCLs and the DLBCL cell line IBL-1. Cells lacking miR-155 are inefficient in progressing through S phase and spontaneously undergo apoptosis. In contrast, three other B-cell lymphoma lines, including two EBV-positive Burkitt's lymphoma cell lines, grew normally in the absence of miR-155 function. These data identify the induction of cellular miR-155 expression by EBV as critical for the growth of both laboratory-generated LCLs and naturally occurring DLBCLs and suggest that targeted inhibition of miR-155 function could represent a novel approach to the treatment of DLBCL in vivo.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 2010

Volume

84

Issue

22

Start / End Page

11670 / 11678

Location

United States

Related Subject Headings

  • Virology
  • MicroRNAs
  • Lymphoma, B-Cell
  • Humans
  • Herpesvirus 4, Human
  • Gene Expression Regulation
  • Cells, Cultured
  • Cell Transformation, Viral
  • Cell Line, Tumor
  • B-Lymphocytes
 

Citation

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Linnstaedt, S. D., Gottwein, E., Skalsky, R. L., Luftig, M. A., & Cullen, B. R. (2010). Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. J Virol, 84(22), 11670–11678. https://doi.org/10.1128/JVI.01248-10
Linnstaedt, Sarah D., Eva Gottwein, Rebecca L. Skalsky, Micah A. Luftig, and Bryan R. Cullen. “Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus.J Virol 84, no. 22 (November 2010): 11670–78. https://doi.org/10.1128/JVI.01248-10.
Linnstaedt SD, Gottwein E, Skalsky RL, Luftig MA, Cullen BR. Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. J Virol. 2010 Nov;84(22):11670–8.
Linnstaedt, Sarah D., et al. “Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus.J Virol, vol. 84, no. 22, Nov. 2010, pp. 11670–78. Pubmed, doi:10.1128/JVI.01248-10.
Linnstaedt SD, Gottwein E, Skalsky RL, Luftig MA, Cullen BR. Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. J Virol. 2010 Nov;84(22):11670–11678.

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

November 2010

Volume

84

Issue

22

Start / End Page

11670 / 11678

Location

United States

Related Subject Headings

  • Virology
  • MicroRNAs
  • Lymphoma, B-Cell
  • Humans
  • Herpesvirus 4, Human
  • Gene Expression Regulation
  • Cells, Cultured
  • Cell Transformation, Viral
  • Cell Line, Tumor
  • B-Lymphocytes