Vesiculovirus neutralization by natural IgM and complement

Mulu Z. Tesfay, Arun Ammayappan, Mark J. Federspiel, Glen N. Barber, David Stojdl, Kah Whye Peng, Stephen J. Russell

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Because of its very low human seroprevalence, vesicular stomatitis virus (VSV) has promise as a systemic oncolytic agent for human cancer therapy. However, as demonstrated in this report, the VSV infectious titer drops by 4 log units during the first hour of exposure to nonimmune human serum. This neutralization occurs relatively slowly and is mediated by the concerted actions of natural IgM and complement. Maraba virus, whose G protein is about 80% homologous to that of VSV, is relatively resistant to the neutralizing activity of nonimmune human serum. We therefore constructed and rescued a recombinant VSV whose G gene was replaced by the corresponding gene from Maraba virus. Comparison of the parental VSV and VSV with Maraba G substituted revealed nearly identical host range properties and replication kinetics on a panel of tumor cell lines. Moreover, in contrast to the parental VSV, the VSV with Maraba G substituted was resistant to nonimmune human serum. Overall, our data suggest that VSV with Maraba G substituted should be further investigated as a candidate for human systemic oncolytic virotherapy applications.

Original languageEnglish (US)
Pages (from-to)6148-6157
Number of pages10
JournalJournal of virology
Volume88
Issue number11
DOIs
StatePublished - Jun 2014

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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