title: Characterization of retroviral and lentiviral vectors pseudotyped with xenotropic murine leukemia virus-related virus envelope glycoprotein.
abstract: Retroviral and lentiviral vectors are effective gene delivery vehicles that are being evaluated in clinical trials. Variations in the viral envelope (Env) glycoproteins, which are used to pseudotype retroviral or lentiviral vectors, can alter vector performance, including stability, titers, host range, and tissue tropism. Xenotropic murine leukemia virus (MLV)-related virus (XMRV) is a novel human retrovirus identified in patients with prostate cancer. XMRV targets XPR1 cell surface receptor, which is expressed in a broad range of human tissues including hematopoietic stem cells. Pseudotyping with XMRV Env would allow targeting of XPR1-expressing tissues. Here, we characterized XMRV Env-pseudotyped retroviral and lentiviral vectors. Although HIV and MLV vectors were poorly pseudotyped with wild-type XMRV Env, replacement of the C-terminal 11 amino acid residues in the transmembrane domain of XMRV Env with the corresponding 6 amino acid residues of amphotropic MLV Env (XMRV/R(ampho)) significantly increased XMRV Env-pseudotyped HIV and MLV vector titers. The transduction efficiency in human CD34(+) cells when using the XMRV/R(ampho)-pseudotyped HIV vector (10-20%) was comparable to that achieved when using the same infectious units of vesicular stomatitis virus G glycoprotein-pseudotyped vector (25%); thus the modified XMRV Env offers an alternative pseudotyping strategy for XPR1-mediated gene delivery.
authors.affiliation: Department of Molecular Medicine, Mayo Clinic, Rochester, 55905, USA.
authors.forename: Toshie
authors.initials: T
authors.lastname: Sakuma
authors.forename: Suk See
authors.initials: SS
authors.lastname: De Ravin
authors.forename: Jason M
authors.initials: JM
authors.lastname: Tonne
authors.forename: Tayaramma
authors.initials: T
authors.lastname: Thatava
authors.forename: Seiga
authors.initials: S
authors.lastname: Ohmine
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ikeda
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D002460:Cell Line; D015925:Cryopreservation; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics*; D019562:Viral Load; D000089842:Xenotropic and Polytropic Retrovirus Receptor; D058008:Xenotropic murine leukemia virus-related virus / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor