A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice

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Most strategies for developing virus-resistant transgenic cells and animals are based on the concept of virus-derived resistance, in which dysfunctional virus-derived products are expressed to interfere with the pathogenic process of the virus in transgenic cells or animals. However, these viral protein targeting approaches are limited because they only target specific viruses and are susceptible to viral mutations. We describe a novel strategy that targets the viral genome itself, rather than viral gene products, to generate virus-resistant transgenic cells and animals. We functionally expressed 3D8 scFv which has both DNase and RNase activities, in HeLa cells and transgenic mice. We found that the transgenic cells and mice acquired complete resistance to two DNA viruses (HSV and PRV) without accumulating the virus, and showed delayed onset of disease symptoms. The antiviral effects against DNA viruses demonstrated in this study were caused by (1) DNase activity of 3D8 scFv in the nucleus, which inhibited DNA replication or RNA transcription and (2) 3D8 scFv RNase activity in the cytoplasm, which blocked protein translation. This strategy may facilitate control of a broad spectrum of viruses, including viruses uncharacterized at the molecular level, regardless of their genome type or variations in gene products.

Vyšlo v časopise: A Nucleic-Acid Hydrolyzing Single Chain Antibody Confers Resistance to DNA Virus Infection in HeLa Cells and C57BL/6 Mice. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004208
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004208

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