New Gene Therapy Removes 90% Latent HSV-1, Which Causes Oral Herpes
Wed, April 21, 2021

New Gene Therapy Removes 90% Latent HSV-1, Which Causes Oral Herpes


Herpes is an infection that results from either of two but similar viruses: herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). It can be spread from skin-to-skin contact with infected areas. Many people with herpes don’t notice the sores or just think of them as something else so they can spread it even if they don’t have any sores or symptoms. According to US Centers for Disease Control and Prevention, there is no cure for herpes yet but there are medications that can shorten or prevent the outbreaks. Now, a promising cure is on the horizon.

Herpes simplex virus type 1 latency

A team of infectious disease researchers Fred Hutchinson Cancer Research Center has used a new gene therapy approach to remove latent HSV-1, which causes genital and mouth ulcers and neonatal herpes. The team said that HSV-1 types 1 and 2 are widespread and increases the risk of acquiring HIV. Once a person is infected at the mucosa or the skin, HSV will establish lifelong latency in both autonomic (major pelvic and superior cervical ganglia) and sensory (dorsal root and trigeminal ganglia) neurons of the peripheral nervous system.

When you say virus latency, a pathogenic virus can lie dormant within a cell. A latent viral infection usually does not cause any noticeable symptoms and can last a long period before becoming active, thus showing symptoms. Like all herpesviruses, the HSV-1 can produce latent or lytic infections, depending on the host cell type.

In the recent study, the researchers used models and they found that with a new gene-editing approach, there has been at least a 90% decrease in the HSV-1 virus latency. Decreasing virus latency at such level, the authors note, is enough to keep the infection from coming back.

Their study, which appeared in the journal Nature Communications, details that the researchers used two sets of genetic scissors to damage the DNA of the virus. Small adjustments were also made in the delivery vehicle to the infected cells and the scientists focused on the nerve pathways that link the neck with the face and eventually reach the tissue where the HSV-1 lies dormant in people with the infection.

Senior author Dr. Keith Jerome, a professor in the Vaccine and Infectious Disease Division at Fred Hutch, told Science Daily that this is the first time that scientists have gone in and eliminated most of the herpes in a body. During their experiments, they target the root cause of the infection, which are the infected cells where the HSV-1 likes dormant. They also target the seeds that allow repeat infections.



Other studies on herpes vs. the team’s gene therapy approach

The authors added that most studies on herpes target suppressing the recurrence of the painful symptoms but their research took a completely different approach as they focused on how to cure the disease itself.

Dr. Jerome, who leads UW Medicine’s Virology Division, added that the big jump in their research is doing it from test tubes to an animal model. He hopes that their study will alter the dialogue around herpes study and opens the idea that we can begin thinking about the cure instead of just controlling the virus.

The World Health Organization says that two-thirds of the world population or 3.7 billion people under age 50 have HSV-1. Another 417 million people ages 15 -49 worldwide have HSV-2.



Regional infection estimates

In 2012, WHO estimates the prevalence of HSV-1 among people aged 0-49 by region. In the Americas: 178 million women (49%) and 142 million men (39%) have HSV-1. The prevalence of HSV-1 in other regions are as follows: Africa: 350 million women (87%), 355 million men (87%), Europe: 207 million women (69%), 187 million men (61%), Eastern Mediterranean: 188 million women (75%), 202 million men (75%), Western Pacific: 488 million women (74%), 521 million men (73%), South-East Asia: 432 million women (59%), 458 million men (58%).

John Hopkins Medicine, which is not involved in the study, also published that 50 to 80% of US adults have oral herpes and about 90% of them have been exposed to the virus by age 50. Specific triggers that can cause oral herpes to recur are unclear but these are the factors that play a role: a recent fever, emotional stress, physical injury, intense or prolonged exposure to sunlight, menstruation, and surgery.

Dr. Jerome and the team went on to say that moving their approach towards clinical application needs a careful examination of its safety. Their result likewise suggests the potential benefits for meganucleases, molecular DNA scissors used to replace, eliminate, or modify sequences in a highly targeted way.



The two types of genetic scissors used to cut herpes virus DNA

The team explained that they used two types of genetic scissors to cut the herpes virus DNA. They said that using just one pair of scissors still allows the virus DNA to be repaired in the infected cell. However, by combining two scissors (meganucleases), it can zero in and cut the segment of herpes DNA. That is when the herpes virus fell apart, they added.

The scientists are also now working on ways to extend their success to HSV-2. For now, antiviral drug acyclovir is recognized to knock down an outbreak of HSV-2 but the virus can still linger for a lifetime within the infected nerve cells. This means that there’s a possibility of reactivation, causing recurrent painful sores on average of two to seven times per year.

Co-author Martine Aubert from the Vaccine and Infectious Disease Division shares that it’s been three or four years of work for their team. Yet, they believe that what they describe in their paper is already a big step to get them closer to considering the gene therapy approach as a curative approach. “It gives us the green light,” he added.

Meanwhile, the American Sexual Health Association shares that close to 90% of people with genital herpes don’t know they have the infection. The nonprofit organization also defines sexual health as “the ability to embrace and enjoy our sexuality throughout our lives. It is an important part of our physical and emotional health.” It said that being sexually healthy also means making an effort to prevent STDs and seek care and treatment when needed.

Creating a cure for HSV-1 is difficult because of the nature of the virus itself. Yet, the new gene therapy approach introduced by the Fred Hutchinson Cancer Research Center researchers provides strong support against latent HSV infections and other chronic infections, such as HIV and HBV.