Retroviral display of functional binding domains fused to the amino terminus of influenza hemagglutinin

Theodora Hatziioannou, Edwige Delahaye, Fransisco Martin, Stephen J. Russell, François Loïc Cosset

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

We have previously shown that retroviral vector particles derived from Moloney murine leukemia virus (MoMuLV) can efficiently incorporate influenza hemagglutinin (HA) glycoproteins from fowl plague virus (FPV), thus conferring a broad tropism to the vectors. To modify its host range, we have engineered the FPV HA to display four different polypeptides on its N terminus: the epidermal growth factor, an anti-human MHC class I molecules scFv (single-chain antibody), an anti-melanoma antigen scFv, and an IgG Fc- binding polypeptide. All recombinant HA glycoproteins were correctly expressed and processed, and efficiently incorporated into Mo-MuLV retroviral particles, indicating that amino-terminal insertion of large polypeptides did not alter the conformation of HA chimeras. Virions carrying the different chimeras bound specifically to cells expressing the targeted cell surface molecules of each ligand. In addition, all virion types were infectious but exhibited various degrees of specificity regarding the use of the targeted cell surface molecule versus the wild-type FPV HA receptor for cell entry and infection. For some ligands tested, infectivity was significantly increased on cells that express the targeted receptor, compared with cells that express only the wild-type HA receptor. Furthermore, some polypeptides could abolish infectivity via the wild-type FPV HA receptor. Our data therefore indicate that it is possible to engineer the HA envelope glycoprotein by fusing ligands to its amino-terminal end without affecting its fusion activity.

Original languageEnglish (US)
Pages (from-to)1533-1544
Number of pages12
JournalHuman gene therapy
Volume10
Issue number9
DOIs
StatePublished - Jun 10 1999

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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