Targeting of a nuclease to murine leukemia virus capsids inhibits viral multiplication.
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.
Natsoulis
G
G
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Seshaiah
P
P
Federspiel
M J
MJ
Rein
A
A
Hughes
S H
SH
Boeke
J D
JD
D016475:3T3 Cells; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism*; D002213:Capsid / Q000378:metabolism*; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000254:growth & development*; D051379:Mice; D008836:Micrococcal Nuclease / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D012367:RNA, Viral / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D014771:Virion / Q000254:growth & development; D014779:Virus Replication
D000998:Antiviral Agents; D015683:Gene Products, gag; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D008836:Micrococcal Nuclease