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

Sarah D. Linnstaedt, Eva Gottwein, Rebecca Skalsky, Micah A. Luftig, Bryan R. Cullen

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

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 laboratorygenerated 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.

Original languageEnglish (US)
Pages (from-to)11670-11678
Number of pages9
JournalJournal of Virology
Volume84
Issue number22
DOIs
StatePublished - Nov 2010
Externally publishedYes

Fingerprint

Human herpesvirus 4
MicroRNAs
Human Herpesvirus 4
microRNA
B-lymphocytes
lymphoma
B-Lymphocytes
cell lines
Cell Line
Lymphoma, Large B-Cell, Diffuse
B-Cell Lymphoma
Epstein-Barr Virus Infections
Burkitt Lymphoma
interphase
infection
Growth
S Phase
apoptosis
Neoplasms
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. / Linnstaedt, Sarah D.; Gottwein, Eva; Skalsky, Rebecca; Luftig, Micah A.; Cullen, Bryan R.

In: Journal of Virology, Vol. 84, No. 22, 11.2010, p. 11670-11678.

Research output: Contribution to journalArticle

Linnstaedt, Sarah D. ; Gottwein, Eva ; Skalsky, Rebecca ; Luftig, Micah A. ; Cullen, Bryan R. / Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus. In: Journal of Virology. 2010 ; Vol. 84, No. 22. pp. 11670-11678.
@article{9d276e1af3404289b0fd27271ad8a691,
title = "Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus",
abstract = "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 laboratorygenerated 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.",
author = "Linnstaedt, {Sarah D.} and Eva Gottwein and Rebecca Skalsky and Luftig, {Micah A.} and Cullen, {Bryan R.}",
year = "2010",
month = "11",
doi = "10.1128/JVI.01248-10",
language = "English (US)",
volume = "84",
pages = "11670--11678",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "22",

}

TY - JOUR

T1 - Virally induced cellular microRNA miR-155 plays a key role in B-cell immortalization by Epstein-Barr virus

AU - Linnstaedt, Sarah D.

AU - Gottwein, Eva

AU - Skalsky, Rebecca

AU - Luftig, Micah A.

AU - Cullen, Bryan R.

PY - 2010/11

Y1 - 2010/11

N2 - 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 laboratorygenerated 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.

AB - 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 laboratorygenerated 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.

UR - http://www.scopus.com/inward/record.url?scp=78049489278&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78049489278&partnerID=8YFLogxK

U2 - 10.1128/JVI.01248-10

DO - 10.1128/JVI.01248-10

M3 - Article

C2 - 20844043

AN - SCOPUS:78049489278

VL - 84

SP - 11670

EP - 11678

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 22

ER -