Viral gene drive spread during herpes simplex virus 1 infection in mice

Walter, M.; Riley, R.; Haick, A. K.; Massa, P. A.; Strongin, D. E.; Klouser, L. M.; Loprieno, M. A.; Stensland, L.; Santo, T. K.; Taylor, M. P.; Jerome, K. R.; Verdin, E.

doi:10.1101/2023.12.07.570711

bioRxiv · 10.1101/2023.12.07.570711

Viral gene drive spread during herpes simplex virus 1 infection in mice

Walter, M.·Riley, R.·Haick, A. K.·Massa, P. A.·Strongin, D. E.·Klouser, L. M.·Loprieno, M. A.·Stensland, L.·Santo, T. K.·Taylor, M. P.·Jerome, K. R.·Verdin, E.

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Abstract

Gene drives are genetic modifications designed to propagate efficiently through a population. Most applications rely on homologous recombination during sexual reproduction in diploid organisms such as insects, but we recently developed a gene drive in herpesviruses that relies on co-infection of cells by wild-type and engineered viruses. Here, we developed a viral gene drive against human herpes simplex virus 1 (HSV-1) and showed that it propagated efficiently in vitro and during HSV-1 infection in mice. We observed high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progressed from the site of inoculation to the peripheral and central nervous systems. In addition, we found evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicated that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study showed that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications.

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Walter, M., Riley, R., Haick, A. K., Massa, P. A., Strongin, D. E., Klouser, L. M., Loprieno, M. A., Stensland, L., Santo, T. K., Taylor, M. P., Jerome, K. R., Verdin, E.. 2023-12-08. Viral gene drive spread during herpes simplex virus 1 infection in mice. https://doi.org/10.1101/2023.12.07.570711

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