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© Michaela Muller-Trutwin
HIV
Publication : Molecular therapy : the journal of the American Society of Gene Therapy

Meganuclease-mediated Inhibition of HSV1 Infection in Cultured Cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular therapy : the journal of the American Society of Gene Therapy - 11 Jan 2011

Grosse S, Huot N, Mahiet C, Arnould S, Barradeau S, Clerre DL, Chion-Sotinel I, Jacqmarcq C, Chapellier B, Ergani A, Desseaux C, Cédrone F, Conseiller E, Pâques F, Labetoulle M, Smith J

Link to Pubmed [PMID] – 21224832

Mol. Ther. 2011 Apr;19(4):694-702

Herpes simplex virus type 1 (HSV1) is a major health problem. As for most viral diseases, current antiviral treatments are based on the inhibition of viral replication once it has already started. As a consequence, they impair neither the viral cycle at its early stages nor the latent form of the virus, and thus cannot be considered as real preventive treatments. Latent HSV1 virus could be addressed by rare cutting endonucleases, such as meganucleases. With the aim of a proof of concept study, we generated several meganucleases recognizing HSV1 sequences, and assessed their antiviral activity in cultured cells. We demonstrate that expression of these proteins in African green monkey kidney fibroblast (COS-7) and BSR cells inhibits infection by HSV1, at low and moderate multiplicities of infection (MOIs), inducing a significant reduction of the viral load. Furthermore, the remaining viral genomes display a high rate of mutation (up to 16%) at the meganuclease cleavage site, consistent with a mechanism of action based on the cleavage of the viral genome. This specific mechanism of action qualifies meganucleases as an alternative class of antiviral agent, with the potential to address replicative as well as latent DNA viral forms.

http://www.ncbi.nlm.nih.gov/pubmed/21224832