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

Fingerprint

Murine Leukemia Viruses
Capsid
Virion
Micrococcal Nuclease
Proteins
Virus Inactivation
Viral Structures
Retroelements
Cell Fusion
Poisons
Viral RNA
Retroviridae
Antiviral Agents
Yeasts
Ions

Keywords

  • antivirals
  • gene therapy
  • staphylococcal nuclease

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Targeting of a nuclease to murine leukemia virus capsids inhibits viral multiplication. / Natsoulis, Georges; Seshaiah, Partha; Federspiel, Mark J.; Rein, Alan; Hughes, Stephen H.; Boeke, Jef D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 2, 17.01.1995, p. 364-368.

Research output: Contribution to journalArticle

Natsoulis, Georges ; Seshaiah, Partha ; Federspiel, Mark J. ; Rein, Alan ; Hughes, Stephen H. ; Boeke, Jef D. / Targeting of a nuclease to murine leukemia virus capsids inhibits viral multiplication. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 2. pp. 364-368.
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