AUG 24, 2020 7:56 AM PDT

Towards a Cure for Latent Herpes 1 Infections

WRITTEN BY: Carmen Leitch

Herpes simplex virus 1 (HSV-1) causes what's popularly known as cold sores, and is transmitted mostly through oral-to-oral contact. It can also cause genital herpes. Once a person is infected with HSV-1, they have it for life. The World Health Organization estimates that globally, 67 percent of people under the age of 50 - 3.7 billion people - have HSV-1 infection. Herpesviruses including HSV-1 can enter a latent phase in which very little virus is. produced in the body and it can remain hidden from the immune system. That also means the virus persists, and at any time can reactivate and cause symptoms or spread.

A computer-generated image of a meganuclease (center), an antibody (left) and CRISPR-Cas9 (right). Ladder-like structures (meganuclease and Cas9) are DNA in the genes they target. / Credit: Abigail Lambert / Stoddard Lab at Fred Hutch

Scientists may have now found a way to eliminate latent HSV-1. Reporting in Nature Communications, scientists delivered enzymes that chop up the HSV-1 DNA into infected cells. These genetic scissors had to reach nerve pathways that link the neck and face, targeting tissue where the virus hides. In a mouse model, there was a 90 percent decrease in the level of the latent virus when using this strategy. The scientists were hopeful that it would be enough to stop symptoms from reemerging.

"This is the first time that scientists have been able to go in and actually eliminate most of the herpes in a body," said the senior study author Dr. Keith Jerome, a professor in the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Research Center. "We are targeting the root cause of the infection: the infected cells where the virus lies dormant and are the seeds that give rise to repeat infections."

The scientists used a viral vector, a common delivery system for gene therapy, to send the DNA-cutting reagents to infected cells. They found that using enzymes called meganucleases to chop up the HSV-1 DNA was a more efficient approach than CRISPR/Cas9. They had to use two meganucleases that only target viral DNA instead of one, but when two were applied to infected cells, the virus could not fix the damage that was inflicted on its genome.

"We use a dual meganuclease that targets two sites on the virus DNA," explained first author Martine Aubert, a senior staff scientist at Fred Hutch. "When there are two cuts, the cells seem to say that the virus DNA is too damaged to be repaired and other molecular players come in to remove it from the cell body."

With this method, there was a 92 percent reduction in the levels of virus in the superior cervical ganglia, where HSV-1 hides.

Instead of trying to stop painful herpes symptoms from recurring, like previous studies, Jerome and his team were interested in finding a cure for the viral infection.

"The big jump here is from doing this in test tubes to doing this in an animal," said Jerome, who also leads the Virology Division at UW Medicine. "I hope this study changes the dialog around herpes research and opens up the idea that we can start thinking about cure, rather than just control of the virus."

Now that they've seen success in their animal model, more work will be needed to bring this to a clinical trial, which may be as soon as three years away. They are also working on a similar strategy for treating herpes simplex 2.

"This is a curative approach for both oral and genital HSV infection," Aubert said. "I see it going into clinical trials in the near future."

Sources: AAAS/Eurekalert! via Fred Hutchinson Cancer Research Center, Nature Communications

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAR 02, 2021
Clinical & Molecular DX
Splice and Dice: Zeroing in on Rare Gene Variants in Alzheimer's
MAR 02, 2021
Splice and Dice: Zeroing in on Rare Gene Variants in Alzheimer's
DNA is the four-letter language that codes for genes, “paragraphs” of DNA information that carry specific in ...
MAR 24, 2021
Genetics & Genomics
Some 'Zombie' Genes Ramp Up Activity in the Brain After Death
MAR 24, 2021
Some 'Zombie' Genes Ramp Up Activity in the Brain After Death
The brain is an organ that needs oxygen to survive, but it's been known that some brain cells can remain active afte ...
APR 09, 2021
Cell & Molecular Biology
CRISPR-SNP Chip Finds Point Mutations in DNA Without PCR
APR 09, 2021
CRISPR-SNP Chip Finds Point Mutations in DNA Without PCR
Some diseases, like sickle-cell anemia and familial amyotrophic lateral sclerosis are due to errors in only a single let ...
APR 12, 2021
Cell & Molecular Biology
Deep Subsurface Microbes Are "Living Fossils"
APR 12, 2021
Deep Subsurface Microbes Are "Living Fossils"
Researchers were shocked when they saw the results of a genetic analysis comparing various microbes from around the worl ...
APR 18, 2021
Genetics & Genomics
The Biology of Autism May Depend on Sex
APR 18, 2021
The Biology of Autism May Depend on Sex
It's been unclear whether boys are diagnosed with autism spectrum disorder more often because of detection issues, or if ...
APR 27, 2021
Genetics & Genomics
A Genetic Path Forward For Endangered Sumatran Rhinos
APR 27, 2021
A Genetic Path Forward For Endangered Sumatran Rhinos
There are fewer than 100 Sumatran rhinoceroses remaining in the world, making this animal one of the world's most endang ...
Loading Comments...