Construction of a gammaretrovirus with a novel tropism and wild-type replication kinetics capable of using human APJ as entry receptor

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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.
Original languageEnglish
JournalJournal of Virology
Volume86
Issue19
Pages (from-to)10621-7
Number of pages7
ISSN0022-538X
DOIs
Publication statusPublished - 2012

    Research areas

  • Amino Acid Sequence, Animals, Flow Cytometry, Gammaretrovirus, Gene Expression Regulation, Viral, HEK293 Cells, Humans, Kinetics, Leukemia Virus, Murine, Mice, Models, Molecular, Molecular Conformation, Molecular Sequence Data, NIH 3T3 Cells, Receptors, G-Protein-Coupled, Receptors, Virus, Sequence Homology, Amino Acid

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