Rhesus lymphocryptovirus latent membrane protein 2A activates beta-catenin signaling and inhibits differentiation in epithelial cells.
Rhesus lymphocryptovirus (LCV) is a gamma-herpesvirus closely related to Epstein-Barr virus (EBV). The rhesus latent membrane protein 2A (LMP2A) is highly homologous to EBV LMP2A. EBV LMP2A activates the phosphatidylinositol 3-kinase (PI3K) and beta-catenin signaling pathways in epithelial cells and affects differentiation. In the present study, the biochemical and biological properties of rhesus LMP2A in epithelial cells were investigated. The expression of rhesus LMP2A in epithelial cells induced Akt activation, GSK3beta inactivation and accumulation of beta-catenin in the cytoplasm and nucleus. The nuclear translocation, but not accumulation of beta-catenin was dependent on Akt activation. Rhesus LMP2A also impaired epithelial cell differentiation; however, this process was not dependent upon Akt activation. A mutant rhesus LMP2A lacking six transmembrane domains functioned similarly to wild-type rhesus LMP2A indicating that the full number of transmembrane domains is not required for effects on beta-catenin or cell differentiation. These results underscore the similarity of LCV to EBV and the suitability of the macaque as an animal model for studying EBV pathogenesis.
Department of Microbiology and Immunology, CB#7290, University of North Carolina-Chapel Hill, 804 Mary Ellen Jones, Chapel Hill, NC 27599-7295, USA.
Catherine A
CA
Siler
Nancy
N
Raab-Traub
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002477:Cells / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000821:virology; D006801:Humans; D018143:Lymphocryptovirus / Q000235:genetics / Q000502:physiology*; D008253:Macaca mulatta; D008565:Membrane Proteins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D014157:Transcription Factors; D014763:Viral Matrix Proteins; D051176:beta Catenin