Summary of TWiV 1119: Gene editing latent herpes

Summary of Scientific Concepts and Discoveries

Gene Editing in Latent Herpes:
The podcast discusses the potential of Gene Editing to manage latent Herpes simplex virus (HSV) infections. Researchers are exploring the use of Mega Nucleases to cut and inactivate viral DNA in neurons, aiming to reduce viral load and shedding.
Research Findings:
The study utilized a mouse model where HSV was established through intravaginal or ocular infection. Mega Nucleases delivered via AAV (adeno-associated virus) vectors showed a significant reduction in HSV viral load in dorsal root ganglia:
- 48-98% reduction in viral load after treatment.
JQ1, a bromo domain inhibitor, was used to reactivate latent HSV, allowing for the assessment of viral shedding post-treatment.
Environmental and Transmission Studies:
A separate study focused on Monkeypox virus (MPXV) shedding and transmission dynamics in humans. Key findings included:
- 100% positivity for viral DNA in skin lesions, with significant presence in rectal and oral swabs.
- Environmental samples (fomites) showed high levels of MPXV DNA, particularly in air conditioning vents and floors.
- The study emphasizes the importance of sanitation and personal protective measures in healthcare settings to prevent transmission.
Immunological Response:
The studies highlighted the immune response to both MPXV and HSV, noting the presence of neutralizing antibodies and the complexities involved in developing effective vaccines.

Methodology Outline

For Gene Editing of HSV:
- Establish latent HSV infection in mice.
- Deliver Mega Nucleases via AAV vectors targeting specific viral genes.
- Assess reduction in viral load and shedding post-treatment using JQ1 for reactivation.
For MPXV Study:
- Conduct a cohort study of patients with confirmed MPXV infections.
- Collect samples from various body sites and environmental fomites.
- Analyze viral DNA presence and antibody responses.

Featured Researchers and Sources

Researchers:
- Yang Yu Shen, Yang Pang, JQ Chen, Chen Hang Wang, Liu (Monkeypox study).
- O. Hake, Stran, Clauser, Leno, Sten, L Santo, Huan Stone, Jerome (HSV study).
Institutions:
- Fred Hutchinson Cancer Center, University of Washington (HSV study).
- Various institutions in China (Monkeypox study).

Additional Notes

The discussions included insights into the mechanisms of viral latency and reactivation, emphasizing the challenges of developing effective vaccines for Herpes viruses. The podcast also touched on the implications of these findings for public health, particularly regarding transmission dynamics in sexually active populations.

Notable Quotes

— 03:02 — « Dog treats are the greatest invention ever. »