Promotion of retroviral entry in the absence of envelope protein by chlorpromazine.
Retrovirus packaging cell lines that express the Moloney murine leukemia virus gag, pol, and env genes and a retroviral vector genome can produce virus particles that are capable of transducing cells. Normally if the packaging cell line does not produce a functional viral fusion glycoprotein, such as the retroviral envelope protein or a foreign viral glycoprotein, then the viruses will be incapable of transducing cells. We have found that incubating envelope protein-deficient virus particles bound to cells with chlorpromazine leads to transduction. Chlorpromazine (CPZ) is a membrane-active reagent that is commonly used to induce the hemifusion to fusion transition when membrane fusion is mediated by partially defective viral glycoproteins. The concentration and pH dependence of the promotion of transduction by CPZ is consistent with a role for CPZ micelle formation in viral entry. These data indicate that caution is warranted when experiments concerning membrane fusion completion promoted by CPZ are analyzed.
Taylor
Gwen M
GM
Department of Biological Sciences, Lilly Hall, 915 W. State Street, Purdue University, West Lafayette, IN 47907, USA.
Zullo
Alfred J
AJ
Larson
Geraldine M
GM
Sanders
David Avram
DA
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015686:Gene Products, env / Q000235:genetics*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000472:pathogenicity*; D041681:NIH 3T3 Cells; D011995:Recombination, Genetic; D014161:Transduction, Genetic
D015686:Gene Products, env; D002746:Chlorpromazine