Targeting of a nuclease to murine leukemia virus capsids inhibits viral multiplication

Georges Natsoulis, Partha Seshaiah, Mark J. Federspiel, Alan Rein, Stephen H. Hughes, Jef D. Boeke

Research output: Contribution to journalArticle

Abstract

Capsid-targeted viral inactivation is an antiviral strategy in which toxic fusion proteins are targeted to virions, where they inhibit viral multiplication by destroying viral components. These fusion proteins consist of a virion structural protein moiety and an enzymatic moiety such as a nuclease. Such fusion proteins can severely inhibit transposition of yeast retrotransposon Ty1, an element whose transposition mechanistically resembles retroviral multiplication. We demonstrate that expression of a murine retrovirus capsid-staphylococcal nuclease fusion protein inhibits multiplication of the corresponding murine leukemia virus by 30- to 100- fold. Staphylococcal nuclease is apparently inactive intracellularly and hence nontoxic to the host cell, but it is active extracellularly because of its requirement for high concentrations of Ca2+ ions. Virions assembled in and shed from cells expressing the fusion protein contain very small amounts of intact viral RNA, as would be predicted for nuclease-mediated inhibition of viral multiplication.

Original languageEnglish (US)
Pages (from-to)364-368
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number2
DOIs
StatePublished - Jan 17 1995

Keywords

  • antivirals
  • gene therapy
  • staphylococcal nuclease

ASJC Scopus subject areas

  • General

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