Development of measles virus-based shielded oncolytic vectors: Suitability of other paramyxovirus glycoproteins

A. W. Hudacek, C. K. Navaratnarajah, R. Cattaneo

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Antibody-mediated neutralization may interfere with the efficacy of measles virus (MV) oncolysis. To circumvent vector neutralization, we sought to exchange the envelope glycoproteins, hemagglutinin (H) and fusion (F), with those from the non-crossreactive Tupaia paramyxovirus (TPMV). To sustain efficient particle assembly, we generated hybrid glycoproteins with the MV cytoplasmic tails and the TPMV ectodomains. Hybrid F proteins that partially retained fusion function, and hybrid H proteins that retained fusion support activity, were generated. However, when used in combination, the hybrid proteins did not support membrane fusion. An alternative strategy was developed based on a hybrid F protein and a truncated H protein that supported cell-cell fusion. A hybrid virus expressing these two proteins was rescued, and was able to spread by cell fusion; however, it was only capable of producing minimal amounts of particles. Lack of specific interactions between the matrix and the H protein, in combination with suboptimal F-protein processing and inefficient glycoprotein transport in the rescue cells, accounted for inefficient particle production. Ultimately, this interferes with applications for oncolytic virotherapy. Alternative strategies for the generation of shielded MV are discussed.

Original languageEnglish (US)
Pages (from-to)109-116
Number of pages8
JournalCancer Gene Therapy
Volume20
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Tupaia paramyxovirus
  • glycoprotein modification
  • measles virus
  • vector shielding

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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