Viral gene drive spread during herpes simplex virus 1 infection in mice
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 report on a viral gene drive against human herpes simplex virus 1 (HSV-1) and show that it propagates efficiently in cell culture and during HSV-1 infection in mice. We describe high levels of co-infection and gene drive-mediated recombination in neuronal tissues during herpes encephalitis as the infection progresses from the site of inoculation to the peripheral and central nervous systems. In addition, we show evidence that a superinfecting gene drive virus could recombine with wild-type viruses during latent infection. These findings indicate that HSV-1 achieves high rates of co-infection and recombination during viral infection, a phenomenon that is currently underappreciated. Overall, this study shows that a viral gene drive could spread in vivo during HSV-1 infection, paving the way toward therapeutic applications.
Authors
- Keith R. Jerome (ORCID: https://orcid.org/0000-0002-8212-3789)
- Lindsay M. Klouser (ORCID: https://orcid.org/0000-0002-9644-361X)
- Laurence Stensland
- Michelle A. Loprieno (ORCID: https://orcid.org/0000-0002-2905-485X)
- Matthew P. Taylor (ORCID: https://orcid.org/0000-0003-0199-7175)
- Eric Verdin (ORCID: https://orcid.org/0000-0003-3703-3183)
- Tracy K. Santo
- Rebeccah Riley (ORCID: https://orcid.org/0000-0002-5870-6837)
- Daniel E. Strongin (ORCID: https://orcid.org/0000-0002-5015-9816)
- Pavitra Roychoudhury (ORCID: https://orcid.org/0000-0002-4567-8232)
- Marius Walter (ORCID: https://orcid.org/0000-0002-2476-9661)
- Martine Aubert (ORCID: https://orcid.org/0000-0003-1125-6856)
- Anoria K. Haick
- Paola A Massa
Institutions
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Infectious Disease Research Institute (US)
- Buck Institute for Research on Aging (US)
- University of Washington (US)
- Montana State University (US)
- Fred Hutch Cancer Center (US)
- University of Washington Applied Physics Laboratory (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-09-17
- DOI
- https://doi.org/10.1038/s41467-024-52395-2
- Citations
- 10
- Primary Topic
- Herpesvirus Infections and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 3.87
Funders
- Fred Hutchinson Cancer Research Center
- Buck Institute for Research on Aging
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases