A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo.
The human gammaherpesvirus Kaposi sarcoma-associated herpesvirus is strongly linked to neoplasms of endothelial and B-cell origin. The majority of tumor cells in these malignancies are latently infected, and latency genes are consequently thought to play a critical role in virus-induced tumorigenesi...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/211c262f0ac742cdb435240a99d41b63 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:211c262f0ac742cdb435240a99d41b63 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:211c262f0ac742cdb435240a99d41b632021-11-18T08:08:10ZA microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo.1932-620310.1371/journal.pone.0049435https://doaj.org/article/211c262f0ac742cdb435240a99d41b632012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23185331/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The human gammaherpesvirus Kaposi sarcoma-associated herpesvirus is strongly linked to neoplasms of endothelial and B-cell origin. The majority of tumor cells in these malignancies are latently infected, and latency genes are consequently thought to play a critical role in virus-induced tumorigenesis. One such factor is kshv-miR-K12-11, a viral microRNA that is constitutively expressed in cell lines derived from KSHV-associated tumors, and that shares perfect homology of its seed sequence with the cellular miR-155. Since miR-155 is overexpressed in a number of human tumors, it is conceivable that mimicry of miR-155 by miR-K12-11 may contribute to cellular transformation in KSHV-associated disease. Here, we have performed a side-by-side study of phenotypic alterations associated with constitutive expression of either human miR-155 or viral miR-K12-11 in bone marrow-derived hematopoietic stem cells. We demonstrate that retroviral-mediated gene transfer and hematopoietic progenitor cell transplantation into C57BL/6 mice leads to increased B-cell fractions in lymphoid organs, as well as to enhanced germinal center formation in both microRNA-expressing mouse cohorts. We furthermore identify Jarid2, a component of Polycomb repressive complex 2, as a novel validated target of miR-K12-11, and confirm its downregulation in miR-K12-11 as well as miR-155 expressing bone marrow cells. Our findings confirm and extend previous observations made in other mouse models, and underscore the notion that miR-K12-11 may have arisen to mimic miR-155 functions in KSHV-infected B-cells. The expression of miR-K12-11 may represent one mechanism by which KSHV presumably aims to reprogram naïve B-cells towards supporting long-term latency, which at the same time is likely to pre-dispose infected lymphocytes to malignant transformation.Christine DahlkeKatrin MaulThomas ChristallaNicole WalzPhilipp SchultCarol StockingAdam GrundhoffPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49435 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Christine Dahlke Katrin Maul Thomas Christalla Nicole Walz Philipp Schult Carol Stocking Adam Grundhoff A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo. |
| description |
The human gammaherpesvirus Kaposi sarcoma-associated herpesvirus is strongly linked to neoplasms of endothelial and B-cell origin. The majority of tumor cells in these malignancies are latently infected, and latency genes are consequently thought to play a critical role in virus-induced tumorigenesis. One such factor is kshv-miR-K12-11, a viral microRNA that is constitutively expressed in cell lines derived from KSHV-associated tumors, and that shares perfect homology of its seed sequence with the cellular miR-155. Since miR-155 is overexpressed in a number of human tumors, it is conceivable that mimicry of miR-155 by miR-K12-11 may contribute to cellular transformation in KSHV-associated disease. Here, we have performed a side-by-side study of phenotypic alterations associated with constitutive expression of either human miR-155 or viral miR-K12-11 in bone marrow-derived hematopoietic stem cells. We demonstrate that retroviral-mediated gene transfer and hematopoietic progenitor cell transplantation into C57BL/6 mice leads to increased B-cell fractions in lymphoid organs, as well as to enhanced germinal center formation in both microRNA-expressing mouse cohorts. We furthermore identify Jarid2, a component of Polycomb repressive complex 2, as a novel validated target of miR-K12-11, and confirm its downregulation in miR-K12-11 as well as miR-155 expressing bone marrow cells. Our findings confirm and extend previous observations made in other mouse models, and underscore the notion that miR-K12-11 may have arisen to mimic miR-155 functions in KSHV-infected B-cells. The expression of miR-K12-11 may represent one mechanism by which KSHV presumably aims to reprogram naïve B-cells towards supporting long-term latency, which at the same time is likely to pre-dispose infected lymphocytes to malignant transformation. |
| format |
article |
| author |
Christine Dahlke Katrin Maul Thomas Christalla Nicole Walz Philipp Schult Carol Stocking Adam Grundhoff |
| author_facet |
Christine Dahlke Katrin Maul Thomas Christalla Nicole Walz Philipp Schult Carol Stocking Adam Grundhoff |
| author_sort |
Christine Dahlke |
| title |
A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo. |
| title_short |
A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo. |
| title_full |
A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo. |
| title_fullStr |
A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo. |
| title_full_unstemmed |
A microRNA encoded by Kaposi sarcoma-associated herpesvirus promotes B-cell expansion in vivo. |
| title_sort |
microrna encoded by kaposi sarcoma-associated herpesvirus promotes b-cell expansion in vivo. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/211c262f0ac742cdb435240a99d41b63 |
| work_keys_str_mv |
AT christinedahlke amicrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT katrinmaul amicrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT thomaschristalla amicrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT nicolewalz amicrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT philippschult amicrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT carolstocking amicrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT adamgrundhoff amicrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT christinedahlke micrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT katrinmaul micrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT thomaschristalla micrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT nicolewalz micrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT philippschult micrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT carolstocking micrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo AT adamgrundhoff micrornaencodedbykaposisarcomaassociatedherpesviruspromotesbcellexpansioninvivo |
| _version_ |
1718422156620070912 |