Construction of a gammaretrovirus with a novel tropism and wild-type replication kinetics capable of using human APJ as entry receptor.
We have constructed a replication-competent gammaretrovirus (SL3-AP) capable of using the human G-protein-coupled receptor hAPJ as its entry receptor. The envelope protein of the virus was made by insertion of the 13-amino-acid peptide ligand for hAPJ, flanked by linker sequences, into one of the variable loops of the receptor binding domain of SL3-2, a murine leukemia virus (MLV) that uses the xenotropic-polytropic virus receptor Xpr1 and which has a host range limited to murine cells. This envelope protein can utilize hAPJ as well as murine Xpr1 for entry into host cells with equal efficiencies. In addition, the SL3-AP virus replicates in cells expressing either of its receptors, hAPJ and murine Xpr1, and causes resistance to superinfection and downregulation of hAPJ in infected cells. Thus, SL3-AP is the first example of a retargeted replication-competent retrovirus, with replication characteristics and receptor interference properties similar to those of natural isolates.
Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark.
Shervin
S
Bahrami
Kristina
K
Pagh
Ditte
D
Ejegod
Mogens
M
Duch
Martin
M
Tolstrup
Finn Skou
FS
Pedersen
D000595:Amino Acid Sequence; D000818:Animals; D000075244:Apelin Receptors; D005434:Flow Cytometry / Q000379:methods; D017988:Gammaretrovirus / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D009052:Leukemia Virus, Murine / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011991:Receptors, Virus / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D000089842:Xenotropic and Polytropic Retrovirus Receptor
C104575:APLNR protein, human; D000075244:Apelin Receptors; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; C000715267:XPR1 protein, human; D000089842:Xenotropic and Polytropic Retrovirus Receptor; C000715268:Xpr1 protein, mouse