Buck Institute, Novato, CA
Viral interference against herpesviruses
The use of defective viruses that interfere with the replication of their infectious parents represents an innovative antiviral strategy. We are developing a CRISPR-based system of viral interference against herpesviruses. Our approach is inspired by the gene drive technology that has been developed in insect species, and can efficiently spread a genetic modification in a target population of herpesviruses. This “viral gene drive” causes the conversion of wildtype viruses into new recombinant viruses and brings the native viral population to extinction. In a proof of principle with human cytomegalovirus, we demonstrated that gene drive viruses can replace their wildtype counterpart in cell culture experiments. We further showed that an interfering virus with severe replicative defects could spread in the viral population and ultimately reduce viral levels. Finally, using Herpes Simplex Virus 1 in a mouse model of viral encephalitis, we are now validating that the strategy can be successful in vivo. Taken together, this work uncovers a novel strategy to suppress a viral infection, as well as a novel way to engineer viruses for therapeutic and research purposes.
- Walter M, Perrone R, Verdin E. Targeting Conserved Sequences Circumvents the Evolution of Resistance in a Viral Gene Drive against Human Cytomegalovirus. J Virol 2021 95(15):e0080221
- Walter M, Verdin E. Viral gene drive in herpesviruses. Nat Commun 2020 11(1):4884
- Walter M, Teissandier A, Pérez-Palacios R, Bourc'his D. An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells. Elife. 2016 Jan 27;5:e11418
Contact: Olivier Neyrolles (Olivier.Neyrolles@ipbs.fr)
For IPBS colleagues, the seminar will take place in the seminar room (max 20 people). Due to the COVID-19-related situation, the seminar is NOT open to persons outside the IPBS.
Link to attend the seminar: https://meet.starleaf.com/4394857183/app
16:00 - 17:00
Seminar room - IPBS | Hybrid conference