title: Direct and efficient cellular transformation of primary rat mesenchymal precursor cells by KSHV.
abstract: 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.affiliation: Tumor Virology Program, Greehey Children’s Cancer Research Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Jones
authors.forename: Fengchun
authors.initials: F
authors.lastname: Ye
authors.forename: Roble
authors.initials: R
authors.lastname: Bedolla
authors.forename: Yufei
authors.initials: Y
authors.lastname: Huang
authors.forename: Jia
authors.initials: J
authors.lastname: Meng
authors.forename: Liwu
authors.initials: L
authors.lastname: Qian
authors.forename: Hongyi
authors.initials: H
authors.lastname: Pan
authors.forename: Fuchun
authors.initials: F
authors.lastname: Zhou
authors.forename: Rosalie
authors.initials: R
authors.lastname: Moody
authors.forename: Brent
authors.initials: B
authors.lastname: Wagner
authors.forename: Mazen
authors.initials: M
authors.lastname: Arar
authors.forename: Shou-Jiang
authors.initials: SJ
authors.lastname: Gao
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002472:Cell Transformation, Viral; D053595:Embryonic Stem Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D008833:Microcirculation; D016366:Open Reading Frames; D051381:Rats; D013997:Time Factors