Back to Search
Start Over
Kaposi's Sarcoma-Associated Herpesvirus Latent Protein LANA Interacts with HIF-1α To Upregulate RTA Expression during Hypoxia: Latency Control under Low Oxygen Conditions.
- Source :
-
Journal of Virology . Aug2006, Vol. 80 Issue 16, p32-32. 1p. - Publication Year :
- 2006
-
Abstract
- Hypoxia can induce lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV) in primary effusion lymphoma (PEL) cells. However, the molecular mechanism of lytic reactivation of KSHV by hypoxia remains unclear. Here we show that the latency-associated nuclear antigen (LANA), which plays a crucial role in modulating viral and cellular gene expression, directly associated with a low oxygen responder, hypoxia-inducible factor-1α (HIF-1α). LANA enhanced not only the transcriptional activities of HIF-1α but also its mRNA level. Coimmunoprecipitation and immunofluorescence studies documented a physical interaction between LANA and HIF-1α in transiently transfected 293T cells as well as in PEL cell lines during hypoxia. Through sequence analysis, several putative hypoxia response elements (HRE-1 to -6) were identified in the essential lytic gene Rta promoter. Reporter assays showed that HRE-2 (-1130 to -1123) and HRE-5 and HRE-6 (+234 to +241 and +812 to +820, respectively, within the intron sequence) were necessary and sufficient for the LANA-mediated HIF-1α response. Electrophoretic mobility shift assays showed HIF-1α-dependent binding of a LANA protein complex specifically to the HRE-2, -5, and -6 motifs within the promoter regulatory sequences. This study demonstrates that hypoxia-induced KSHV lytic replication is mediated at least in part through cooperation of HIF-1α with LANA bound to the HRE motifs of the Rta promoter. [ABSTRACT FROM AUTHOR]
- Subjects :
- *HYPOXEMIA
*KAPOSI'S sarcoma
*SARCOMA
*LYMPHOMAS
*ANTIGENS
Subjects
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 80
- Issue :
- 16
- Database :
- Academic Search Index
- Journal :
- Journal of Virology
- Publication Type :
- Academic Journal
- Accession number :
- 21866172
- Full Text :
- https://doi.org/10.1128/JVI.00689-06