Inhibition of the phosphatidylinositol 3-kinase-Akt pathway enhances gamma-2 herpesvirus lytic replication and facilitates reactivation from latency Journal Article

   

Authors:	Peng, L.; Wu, T. T.; Tchieu, J. H.; Feng, J.; Brown, H. J.; Li, X.; Qi, J.; Deng, H.; Vivanco, I.; Melinghoff, I. K.; Jamieson, C.; Sun, R.
Article Title:	Inhibition of the phosphatidylinositol 3-kinase-Akt pathway enhances gamma-2 herpesvirus lytic replication and facilitates reactivation from latency
Abstract:	Cellular signalling pathways are critical in regulating the balance between latency and lytic replication of herpesviruses. Here, we investigated the effect of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway on replication of two gamma-2 herpesviruses, murine gammaherpesvirus-68 (MHV-68) and human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). We found that de novo infection of MHV-68 induced PI3K-dependent Akt activation and the lytic replication of MHV-68 was enhanced by inhibiting the PI3K-Akt pathway with both chemical inhibitors and RNA interference technology. Inhibiting the activity of Akt using Akt inhibitor VIII also facilitated the reactivation of KSHV from latency. Both lytic replication and latency depend on the activity of viral transactivator RTA and we further show that the activity of RTA is increased by reducing Akt1 expression. The data suggest that the PI3K-Akt pathway suppresses the activity of RTA and thereby contributes to the maintenance of viral latency and promotes tumorigenesis. © 2010 SGM.
Keywords:	signal transduction; protein kinase b; protein expression; genetics; nonhuman; mouse; animal; metabolism; animals; mice; enzyme inhibition; cell line; rna interference; enzyme activation; phosphatidylinositol 3 kinase; physiology; virology; transactivator protein; 1-phosphatidylinositol 3-kinase; proto-oncogene proteins c-akt; herpes virus; herpesviridae; murinae; trans-activators; virus replication; virus latency; cell strain 3t3; human herpesvirus 8; 3t3 cells; virus reactivation; virus protein; viral proteins; virus activation; protein kinase b inhibitor; gammaherpesvirinae; herpes virus infection; murine hepatitis virus; herpesviridae infections
Journal Title:	Journal of General Virology
Volume:	91
Issue:	2
ISSN:	0022-1317
Publisher:	Soc General Microbiology
Date Published:	2010-02-01
Start Page:	463
End Page:	469
Language:	English
DOI:	10.1099/vir.0.015073-0
PUBMED:	19864499
PROVIDER:	scopus
PMCID:	PMC2888311
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-76249099841&partnerID=40&md5=647678c1b58a053893a211df8b3af0bd
Notes:	--- - "Cited By (since 1996): 4" - "Export Date: 20 April 2011" - "CODEN: JGVIA" - "Source: Scopus"

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