cis-Active elements of Friend spleen focus-forming virus: from disease induction to disease prevention.
The polycythemic strain of the Friend spleen focus-forming virus (SFFVp) is a replication-defective, acutely transforming retrovirus inducing a bistage erythroleukemia in susceptible mice. The first stage of the disease is an acute polyclonal erythroblastosis induced by the proliferation-promoting effect of gp55. gp55 is expressed from a spliced subgenomic message of SFFVp and stimulates the cellular receptor for erythropoietin. Using a selectable SFFVp that otherwise mimics the specificity of the disease, we demonstrate that the kinetics of the polyclonal expansion depends on the transcriptional strength of the retroviral cis-active elements. By exchanging gp55 for apathogenic genes, we show that SFFVp enhancer and splice signals can be successfully utilized for the development of retroviral vectors mediating very efficient transgene expression in hematopoietic cells. Apathogenic selectable SFFVp-based vectors carrying distinct enhancer alterations are a valuable tool to analyze transcriptional control of leukemia viruses in the absence of oncogenic proteins. Moreover they might have therapeutic potential.
Baum
C
C
Department of Cell and Virus Genetics, Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Germany.
Hunt
N
N
Hildinger
M
M
Eckert
H G
HG
Zaehres
H
H
Richters
A
A
John
J
J
Löhler
J
J
Ostertag
W
W
D000818:Animals; D004742:Enhancer Elements, Genetic; D004920:Erythropoiesis; D005622:Friend murine leukemia virus / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000821:virology; D007942:Leukemia, Experimental / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control; D051379:Mice; D012326:RNA Splicing; D012367:RNA, Viral / Q000235:genetics*; D051381:Rats; D012091:Repetitive Sequences, Nucleic Acid; D012192:Retroviridae Infections / Q000235:genetics; D013155:Spleen Focus-Forming Viruses / Q000235:genetics*; D014161:Transduction, Genetic; D014412:Tumor Virus Infections / Q000235:genetics*
D012367:RNA, Viral