Document Detail


Direct and efficient cellular transformation of primary rat mesenchymal precursor cells by KSHV.
MedLine Citation:
PMID:  22293176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Infections by viruses are associated with approximately 12% of human cancer. Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several malignancies commonly found in AIDS patients. The mechanism of KSHV-induced oncogenesis remains elusive, due in part to the lack of an adequate experimental system for cellular transformation of primary cells. Here, we report efficient infection and cellular transformation of primary rat embryonic metanephric mesenchymal precursor cells (MM cells) by KSHV. Cellular transformation occurred at as early as day 4 after infection and in nearly all infected cells. Transformed cells expressed hallmark vascular endothelial, lymphatic endothelial, and mesenchymal markers and efficiently induced tumors in nude mice. KSHV established latent infection in MM cells, and lytic induction resulted in low levels of detectable infectious virions despite robust expression of lytic genes. Most KSHV-induced tumor cells were in a latent state, although a few showed heterogeneous expression of lytic genes. This efficient system for KSHV cellular transformation of primary cells might facilitate the study of growth deregulation mechanisms resulting from KSHV infections.
Authors:
Tiffany Jones; Fengchun Ye; Roble Bedolla; Yufei Huang; Jia Meng; Liwu Qian; Hongyi Pan; Fuchun Zhou; Rosalie Moody; Brent Wagner; Mazen Arar; Shou-Jiang Gao
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-01
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  122     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-02     Completed Date:  2012-04-30     Revised Date:  2013-05-20    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1076-81     Citation Subset:  AIM; IM    
Affiliation:
Tumor Virology Program, Greehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Culture Techniques
Cell Line
Cell Transformation, Viral
Embryonic Stem Cells / cytology*
Gene Expression Regulation*
Herpesvirus 8, Human / metabolism*
Human Umbilical Vein Endothelial Cells
Humans
Mesenchymal Stromal Cells / cytology*
Mice
Mice, Nude
Microcirculation
Open Reading Frames
Rats
Time Factors
Grant Support
ID/Acronym/Agency:
CA096512/CA/NCI NIH HHS; CA124332/CA/NCI NIH HHS; CA132637/CA/NCI NIH HHS; R01 CA096512-06/CA/NCI NIH HHS; R01 CA096512-07/CA/NCI NIH HHS; R01 CA096512-08/CA/NCI NIH HHS; R01 CA096512-09/CA/NCI NIH HHS; R01 CA124332-01A2/CA/NCI NIH HHS; R01 CA124332-02/CA/NCI NIH HHS; R01 CA124332-03/CA/NCI NIH HHS; R01 CA124332-04/CA/NCI NIH HHS; R01 CA124332-05/CA/NCI NIH HHS; R01 CA124332-06/CA/NCI NIH HHS; R01 CA132637-01A1/CA/NCI NIH HHS; R01 CA132637-02/CA/NCI NIH HHS; R01 CA132637-02S1/CA/NCI NIH HHS; R01 CA132637-03/CA/NCI NIH HHS; R01 CA132637-03S1/CA/NCI NIH HHS; R01 CA132637-04/CA/NCI NIH HHS; R01 CA132637-04S1/CA/NCI NIH HHS; R01 CA132637-05/CA/NCI NIH HHS; R01 CA132637-06/CA/NCI NIH HHS
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