Jaagsiekte sheep retrovirus Env protein stabilizes retrovirus vectors against inactivation by lung surfactant, centrifugation, and freeze-thaw cycling.
Jaagsiekte sheep retrovirus (JSRV) replicates in the lungs of sheep and causes the secretion of copious lung fluid containing the virus. Adaptation of JSRV to infection and replication in the lung and its apparent resistance to the denaturing activity of lung fluid suggest that vectors based on JSRV would be useful for gene therapy targeted to the lung. We show here that a retrovirus vector bearing the JSRV Env is stable during treatment with lung surfactant while an otherwise identical vector bearing an amphotropic Env is inactivated. Furthermore, the JSRV vector was stable during centrifugation, allowing facile vector concentration, and showed no loss of activity after six freeze-thaw cycles. However, the JSRV vector was inactivated by standard disinfectants, indicating that JSRV vectors pose no unusual safety risk related to their improved stability under other conditions.
Coil
D A
DA
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Strickler
J H
JH
Rai
S K
SK
Miller
A D
AD
D000818:Animals; D001688:Biological Products; D002498:Centrifugation; D005615:Freezing; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D015684:Gene Products, pol / Q000235:genetics / Q000378:metabolism; D005822:Genetic Vectors / Q000187:drug effects; D006801:Humans; D022141:Jaagsiekte sheep retrovirus / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D008979:Moloney murine leukemia virus; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D012756:Sheep; D014407:Tumor Cells, Cultured; D014775:Virus Activation
D001688:Biological Products; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D011663:Pulmonary Surfactants; C072197:beractant