KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA.
Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2009
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9cccbbca394040a6aa99a96faf1f7381 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:9cccbbca394040a6aa99a96faf1f7381 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:9cccbbca394040a6aa99a96faf1f73812021-11-25T05:47:13ZKSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA.1553-73661553-737410.1371/journal.ppat.1000324https://doaj.org/article/9cccbbca394040a6aa99a96faf1f73812009-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19266083/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while in the productive infection the virus is reactivated with initiation of extensive viral DNA replication and gene expression, resulting in production of new viral particles. Viral reactivation is crucial for KSHV pathogenesis and contributes to the progression of KS. We have recently identified Pim-1 as a kinase reactivating KSHV upon over-expression. Here we show that another Pim family kinase, Pim-3, also induces viral reactivation. We demonstrate that expression of both Pim-1 and Pim-3 is induced in response to physiological and chemical reactivation in naturally KSHV-infected cells, and we show that they are required for KSHV reactivation under these conditions. Furthermore, our data indicate that Pim-1 and Pim-3 contribute to viral reactivation by phosphorylating the KSHV latency-associated nuclear antigen (LANA) on serine residues 205 and 206. This counteracts the LANA-mediated repression of the KSHV lytic gene transcription. The identification of Pim family kinases as novel cellular regulators of the gammaherpesvirus life cycle facilitates a deeper understanding of virus-host interactions during reactivation and may represent potential novel targets for therapeutic intervention.Fang ChengMagdalena Weidner-GlundeMarkku VarjosaloEeva-Marja RainioAnne LehtonenThomas F SchulzPäivi J KoskinenJussi TaipalePäivi M OjalaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 3, p e1000324 (2009) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Fang Cheng Magdalena Weidner-Glunde Markku Varjosalo Eeva-Marja Rainio Anne Lehtonen Thomas F Schulz Päivi J Koskinen Jussi Taipale Päivi M Ojala KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. |
| description |
Host signal-transduction pathways are intimately involved in the switch between latency and productive infection of herpes viruses. As with other herpes viruses, infection by Kaposi's sarcoma herpesvirus (KSHV) displays these two phases. During latency only few viral genes are expressed, while in the productive infection the virus is reactivated with initiation of extensive viral DNA replication and gene expression, resulting in production of new viral particles. Viral reactivation is crucial for KSHV pathogenesis and contributes to the progression of KS. We have recently identified Pim-1 as a kinase reactivating KSHV upon over-expression. Here we show that another Pim family kinase, Pim-3, also induces viral reactivation. We demonstrate that expression of both Pim-1 and Pim-3 is induced in response to physiological and chemical reactivation in naturally KSHV-infected cells, and we show that they are required for KSHV reactivation under these conditions. Furthermore, our data indicate that Pim-1 and Pim-3 contribute to viral reactivation by phosphorylating the KSHV latency-associated nuclear antigen (LANA) on serine residues 205 and 206. This counteracts the LANA-mediated repression of the KSHV lytic gene transcription. The identification of Pim family kinases as novel cellular regulators of the gammaherpesvirus life cycle facilitates a deeper understanding of virus-host interactions during reactivation and may represent potential novel targets for therapeutic intervention. |
| format |
article |
| author |
Fang Cheng Magdalena Weidner-Glunde Markku Varjosalo Eeva-Marja Rainio Anne Lehtonen Thomas F Schulz Päivi J Koskinen Jussi Taipale Päivi M Ojala |
| author_facet |
Fang Cheng Magdalena Weidner-Glunde Markku Varjosalo Eeva-Marja Rainio Anne Lehtonen Thomas F Schulz Päivi J Koskinen Jussi Taipale Päivi M Ojala |
| author_sort |
Fang Cheng |
| title |
KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. |
| title_short |
KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. |
| title_full |
KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. |
| title_fullStr |
KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. |
| title_full_unstemmed |
KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. |
| title_sort |
kshv reactivation from latency requires pim-1 and pim-3 kinases to inactivate the latency-associated nuclear antigen lana. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2009 |
| url |
https://doaj.org/article/9cccbbca394040a6aa99a96faf1f7381 |
| work_keys_str_mv |
AT fangcheng kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT magdalenaweidnerglunde kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT markkuvarjosalo kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT eevamarjarainio kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT annelehtonen kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT thomasfschulz kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT paivijkoskinen kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT jussitaipale kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana AT paivimojala kshvreactivationfromlatencyrequirespim1andpim3kinasestoinactivatethelatencyassociatednuclearantigenlana |
| _version_ |
1718414473714204672 |