A cure for herpes? There is progress to report (2023)

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A cure for herpes? There is progress to report (1)

It takes a persistent scientist to stop a persistent virus.

A decade ago, Fred Hutchinson Cancer Research Center virologist Dr. Keith Jerome began exploring the idea that lifelong infections with herpes viruses might be cured by using the DNA-cutting tools of gene therapy.

Initial research showed these techniques could knock out small quantities of latent virus, and the work of improving the results fell to Jerome’s senior staff scientist, Dr. Martine Aubert. Five years ago, the team reported they had damaged the genes of 2%-4% of herpes virus in infected mice. Aubert’s work was an important proof of principle, but far short of a cure.

Nevertheless, she persisted.

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On Aug. 18, the team led by Jerome and Aubert published a paper inNature Communicationsshowing that, through a series of incremental improvements on their original method, they had destroyed up to 95% of herpes virus lurking in certain nerve clusters of mice.

“This is the first time that anybody has been able to go in and actually eliminate most of herpes in a body,” said Jerome, who is also spearheading research at Fred Hutch and the University of Washington on COVID-19. “It is a completely different approach to herpes therapy than anybody’s ever had before.”

The hidden herpes viruses are disabled by an injection that tracks down infected nerve cells and induces them to make special gene-cutting enzymes, which work like a molecular scissors, to slash viral genes in specific places. Much of the team’s meticulous work of the past five years has involved finding better ways to target infected clusters of nerve cells and to thwart the virus’s ability to quickly repair the cuts to its genes.

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Whereas most research on herpes has focused on suppressing the recurrence of painful symptoms, the Fred Hutch gene therapy work addresses the root cause of reactivation: the presence of latent virus in infected nerve cells.

“I hope that this study changes the dialogue around herpes research and opens up the idea that we can start thinking about cure, rather than just control of the virus,” Jerome said.

It will still take a long time before these experiments lead to the first human trials of gene therapy to cure herpes. Jerome estimates that will be at least three years away.

Herpes simplex viruses afflict billions of human beings around the globe. According to the World Health Organization, two-thirds of the world population under the age of 50 carry herpes simplex virus type 1, or HSV-1, which primarily causes cold sores, while 491 million people aged 15-49 are infected with closely related HSV-2, which is the cause of sexually transmitted genital herpes.

Although the antiviral drug acyclovir can knock down an outbreak of HSV-2, the virus lingers for a lifetime within infected nerve cells and may reactivate, causing recurrent bouts of painful sores, on average, two to seven times per year. The prevalence of this chronic disease increases with age. Less than 1% of teens in the United States are infected, but that increases to 21% of Americans in their 40s, according to the Centers for Disease Control and Prevention. HSV-2 infection not only complicates the sex lives of couples, it also increases a person’s susceptibility to HIV, the virus that causes AIDS.

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The Jerome Lab’s herpes research thus far involves only HSV-1, but the scientists are now working on ways to extend their success to HSV-2. The first step will be to repeat their experiments using HSV-2 in guinea pigs, which, unlike mice, experience natural reactivations of herpes virus infections, just as humans do.

Improvements in gene-editing tools — and patience — keys to success

The advances in herpes cure research over the past five years are largely due to a series of improvements in the gene editing tools. First, the researchers added combinations of different gene-cutting enzymes. The more cuts these molecular scissors make, the harder it is for the virus to recover.

Second, they chose different strains of harmless carrier viruses that do a better job of transporting those cutting tools to the places in the body where infected nerve cells are clustered.

“It’s been three or four years of work, but I think what we describe in the paper is a really big step,” said Aubert. “It gets us closer to really considering this as a curative approach. It gives us the green light.”

Since the earliest days of the experiments, the Jerome team learned to rely on a cutting enzyme called a “meganuclease” that can zero in on a segment of herpes DNA and cut both strands of the double helix. Despite the “mega” in its name, these scissors are extraordinarily small — about half the size of an antibody, those tiny, Y-shaped proteins our immune system uses to swarm over and disable viruses and bacteria.

It will still take a long time before these experiments lead to the first human trials of gene therapy to cure herpes. Jerome estimates that will be at least three years away.

The team attained its first promising results years ago using a single type of meganuclease that proved effective in cutting the herpes virus DNA, but the results were short-lived. The virus could rely on the infected cells’ own DNA-repair programs — which don’t distinguish between viral genes from their own — to fix the break most of the time.

But over time, the researchers found that they could eliminate up to 90% of the latent virus by using a mix of two or three different meganucleases. It is simply harder to repair two breaks than one. With more tinkering, the results continued to improve.

A workhorse of gene therapy

The researchers also refined their methods of transporting the molecular scissors to targeted nerve cells. From the beginning, Jerome and his team have relied on a harmless, hollowed-out virus that is drawn to the surface proteins of nerve cells. Called an adeno-associated virus vector, or AAV, it is the little workhorse of gene therapy. In this case, it is used to ferry to the infected nerve cells genetic instructions that cause them to make those meganucleases.

“We inject the AAV vector, and it finds its way,” Aubert said.

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Latent herpes viruses lurk in clusters of nerve cells called ganglia, and researchers have found that some ganglia are harder to reach than others. Over the years, they discovered that some AAV strains are better suited than others to find specific types of nerve clusters, and this has helped them fine-tune the selection of these delivery viruses to match infected cells in different places.

In their mouse experiments, the team continued to improve their results, nudging them up to a 95% reduction in herpesvirus infection in one prominent nerve cluster using a selection of two different meganucleases carried by three different flavors of AAVs. By selecting vectors that are primed for harder-to-reach nerve clusters, the group expects to continue improving their ability to eradicate the virus.

A cure for herpes? There is progress to report (3)

As the Jerome Lab prepares to see if its gene therapy can block genital herpes, they are also reshuffling their selection of vector viruses and meganucleases to target nerve cells infected by HSV-2. They are collaborating with Dr. Barry Stoddard, a Hutch colleague who specializes in discovering the structure of proteins, to custom-design a set of meganucleases that they hope will work even better than the first.

“The three enzymes they use already work pretty well, but one doesn’t quite work as well as the others,” Stoddard said. “We’re looking at the structure and determining a few changes to improve performance.”

Stoddard is also tweaking the meganucleases’ structures to make them a better fit against HSV-2.

In their latest paper, the team evaluated the use of a newer and more glamorous gene-cutting tool, CRISPR-Cas9. Somewhat surprisingly, they found that this newfangled precision cutting tool did not perform as well as their meganucleases. One possible reason: CRISPR is a much larger molecule, and the comparatively smaller meganucleases are easier to package and deliver to nerve cells.

A cure for herpes? There is progress to report (4)

Stoddard said that meganucleases can also more accurately zero in on their target genes than CRISPR, which is known for its “off-target” effects — cutting the wrong gene. The advantage of CRISPR is that it can be designed quickly, while meganucleases are laborious to make.

”It can take a day to make a new CRISPR. It takes about three months to make a meganuclease," Stoddard said.

Experience has shown, however, that the Jerome Lab is endowed with patience. Their 10-year trek has proven the potential of gene therapy for erasing herpes, yet the road ahead will undoubtedly require deep reserves of patience and persistence.

Aubert said that comes naturally to her.

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“I don’t like to leave things unfinished, personally. I am like that,” she said.

The research was supported by the Caladan Foundation and the National Institutes of Health. Meganucleases used in the experiments described in the Nature Communications paper were supplied by Paris-based Cellectis SA.

Note: Scientists at Fred Hutch played a role in developing these discoveries, and Fred Hutch and certain of its scientists may benefit financially from this work in the future.

Have a question about Fred Hutch herpes research? Please contact HSV@fredhutch.org.

Sabin Russell is a staff writer at Fred Hutchinson Cancer Center. For two decades he covered medical science, global health and health care economics for theSan Francisco Chronicle, and wrote extensively about infectious diseases, including HIV/AIDS. He was a Knight Science Journalism Fellow at MIT, and a freelance writer for the New York Times and Health Affairs. Reach him atsrussell@fredhutch.org.

Are you interested in reprinting or republishing this story? Be our guest! We want to help connect people with the information they need. We just ask that you link back to the original article, preserve the author’s byline and refrain from making edits that alter the original context. Questions? Email us atcommunications@fredhutch.org

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FAQs

Are they close to finding a cure for herpes? ›

There is currently no cure or preventive treatment for herpes infection. If a person gets either form of herpes virus infection, they will have it for life, whether or not they experience symptoms.

How long until there is a cure for herpes? ›

It will still take a long time before these experiments lead to the first human trials of gene therapy to cure herpes. Jerome estimates that will be at least three years away. Herpes simplex viruses afflict billions of human beings around the globe.

Is there a cure for herpes in 2022? ›

Symptoms of genital herpes can be eased with antiviral drugs. But there are no vaccinations against herpes. There is no cure.

Can you live a normal life after herpes? ›

People with herpes have relationships and live totally normal lives. There are treatments for herpes, and there's a lot you can do to make sure you don't give herpes to anyone you have sex with. Millions and millions of people have herpes — you're definitely not alone.

Does herpes worsen with age? ›

It might be annoying, but herpes doesn't get worse over time or cause serious health problems like other STDs can. If you don't get treated for herpes, you might keep having regular outbreaks, or they could only happen rarely. Some people naturally stop getting outbreaks after a while.

How do you keep herpes dormant? ›

Reducing Outbreaks
  1. Get plenty of sleep. This helps keep your immune system strong.
  2. Eat healthy foods. Good nutrition also helps your immune system stay strong.
  3. Keep stress low. Constant stress can weaken your immune system.
  4. Protect yourself from the sun, wind, and extreme cold and heat.

Can shingles vaccine help with herpes? ›

Does the herpes zoster vaccine protect you from genital herpes? No. The herpes zoster vaccine protects you against shingles (herpes zoster), a viral infection that is a reactivation of the chickenpox virus. 14 There is currently no vaccine to protect against genital or oral herpes.

Are herpes blood tests accurate? ›

Herpes blood tests have a sensitivity level of about 80-98%. This type of test detects antibodies to the herpes virus, so it may not be as accurate when performed soon after infection.

Does herpes affect your organs? ›

Herpes can also spread to internal organs, such as the liver and lungs. Infants infected with herpes are treated with acyclovir, an antiviral drug. They usually receive several weeks of intravenous acyclovir treatment, often followed by several months of oral acyclovir.

How do people live with herpes? ›

Life Goes On

Brayer encourages the same safe practices for both oral and genital herpes: Don't share personal care items. During outbreaks, avoid infecting others. For genital herpes, forgo sex or use condoms from the first signs of an outbreak until the sores clear up. Also consider your communication options.

What medication can you take daily for herpes? ›

Treatment for Genital Herpes

Acyclovir: The oldest antiviral medication for herpes is acyclovir. It has been available since 1982 in a topical form (as an ointment) and sold since 1985 in pill form. Acyclovir has been shown to be safe in persons who have used it continuously (every day) for as long as 10 years.

What is the chance of spreading herpes when no outbreak? ›

But it is still possible to spread the infection even when no ulcers are present. One study examined rates of genital herpes transmission in heterosexual couples when only one partner was initially infected [1]. Over one year, the virus was transmitted to the other partner in 10 percent of couples.

How do mentally deal with herpes? ›

Keep in mind the following: Realize that it's normal to be stressed emotionally by herpes, especially at first. Give yourself time to adjust, and remember that the emotional issues will get easier. Try to keep in mind that genital herpes is somewhat like other infections you may have had in the past.

Can people with herpes have kids? ›

The answer to both questions is “yes,” but you'll need to take some precautions. Women with genital herpes can have healthy children. If you have genital herpes, precautions can help prevent your baby from getting the virus.

What happens to old people with herpes? ›

Herpes simplex virus (HSV) most commonly affects the genital and perioral regions. In the elderly, HSV infection is typically manifest at the vermilion border of the lip. The main concern of recurrent herpes labialis in the elderly is related to potential autoinoculation of the eye or genital area.

Does herpes make your VAG smell? ›

A person experiencing herpes discharge will notice that it is different from that of a normal discharge. It has a strong, foul, and pungent odor in both men and women, generally described as “fishy”.

Does herpes affect your brain? ›

Key points. Herpes meningoencephalitis is an infection of the brain and brain covering (meninges) caused by the herpes simplex virus. It is a medical emergency that requires treatment right away.

What soap is good for herpes? ›

Self-Care Procedures for Genital Herpes: Bathe the affected genital area twice a day with mild soap and water. Gently pat dry with a towel or use a hair dryer set on warm. Using Aveeno (colloidal oatmeal soap or bath treatments) may also be soothing.

Does yeast infection cream help herpes? ›

The bottom line. Herpes and yeast infections are two separate conditions that require different treatments. If you're not sure you have a yeast infection, it's best to seek a doctor's diagnosis before self-treating with over-the-counter yeast infection medication.

Is herpes a sperm? ›

Most of the human herpesviruses can be found in semen, although the reported prevalence varies considerably between individual studies. The frequent presence of herpesvirus in semen raises the question whether sexual transmission of the virus could have an impact on human reproduction.

What diseases are caused by herpes virus? ›

Mucocutaneous manifestations of herpes simplex virus infection include gingivostomatitis, herpes genitalis, herpetic keratitis, and dermal whitlows. Neonatal herpes simplex virus infection and herpes simplex virus encephalitis also occur.

Can herpes turn into shingles? ›

The condition we call shingles is caused by herpes zoster. Herpes zoster is the same viral infection that causes chicken pox, and the herpes zoster virus can live in the body for years after the case of chicken pox is gone, and re-emerge as the painful blisters of shingles.

Can you get shingles in your private parts? ›

A person can get shingles on the genital area, but this is uncommon. Aside from blisters, genital shingles may also cause bladder and bowel problems. While shingles can cause genital lesions, other conditions, such as syphilis and genital herpes, can also have a similar presentation.

Do most people test positive for herpes? ›

"For HSV-1, close to 100 percent of people in the U.S. are antibody-positive because they have been exposed at some point in their lives, though only a percentage of these individuals will actually get cold sores," says Adam Friedman, the residency program director at the George Washington University School of Medicine ...

Can a urine test detect herpes? ›

Does Herpes show in a urine test? Herpes will show in a urine test if and only if you have symptoms at the time of the test. So, a positive urine test means that you do have herpes. If it is negative, it means you did not have an outbreak at the time of the test.

Are some people immune herpes? ›

In Short, No, You Can't Be Immune to Herpes

Current scientific research shows that herpes is highly contagious and that everyone is at risk of infection. It's also extremely common, infecting anywhere from more than 50% of people (in the case of HSV-1) to around 11% of people (in the case of HSV-2).

Can herpes live on towels? ›

In some rare instances, oral herpes can be transmitted via contaminated hard objects, such as a cup, toothbrush, or lipstick. Herpes can't live or thrive on porous surfaces, such as a towel. For this reason, you can't get oral or genital herpes from using someone else's towel.

Can herpes live on sheets? ›

Think of it this way: In general, the herpes virus needs to be inside the human body to survive—it dies quickly on the surfaces of inanimate objects like toilet seats, according to the American Sexual Health Association (ASHA).

How long herpes live on towels? ›

A California pediatrician has shown that the genital herpes virus, the most common cause of serious venereal disease in this country, can live for up to 72 hours on inanimate objects, such as cotton fabric.

What percent of population has herpes? ›

How common is genital herpes? Genital herpes infection is common in the United States. CDC estimated that there were 572,000 new genital herpes infections in the United States in a single year. Nationwide, 11.9 % of persons aged 14 to 49 years have HSV-2 infection (12.1% when adjusted for age).

Can shingles vaccine help with herpes? ›

Does the herpes zoster vaccine protect you from genital herpes? No. The herpes zoster vaccine protects you against shingles (herpes zoster), a viral infection that is a reactivation of the chickenpox virus. 14 There is currently no vaccine to protect against genital or oral herpes.

Is there a vaccine for herpes? ›

Although several candidate HSV vaccines have been tested in humans, currently there are no licensed vaccines against either HSV type.

How likely is it to spread herpes? ›

One study examined rates of genital herpes transmission in heterosexual couples when only one partner was initially infected [1]. Over one year, the virus was transmitted to the other partner in 10 percent of couples. In 70 percent of cases, infection occurred at a time when there were no symptoms.

What country has the highest rate of herpes? ›

HSV-2 is more common in Sub-Saharan Africa than in Europe or the North America. Up to 82% of women and 53% of men in Sub-Saharan Africa are seropositive for HSV-2. These are the highest levels of HSV-2 infection in the world, although exact levels vary from country to country in this continent.

Where is herpes most common in the world? ›

Herpes simplex virus type 2 (HSV-2) is a common infection in many countries, with prevalence in some regions, such as sub-Saharan Africa, higher than in the USA. Prevalence in adult general populations in sub-Saharan Africa ranges from 30% to 80% in women, and from 10% to 50% in men.

Why do so many people have herpes? ›

Why Do So Many People Have Herpes? - YouTube

What diseases are caused by herpes virus? ›

Mucocutaneous manifestations of herpes simplex virus infection include gingivostomatitis, herpes genitalis, herpetic keratitis, and dermal whitlows. Neonatal herpes simplex virus infection and herpes simplex virus encephalitis also occur.

Can herpes turn into shingles? ›

The condition we call shingles is caused by herpes zoster. Herpes zoster is the same viral infection that causes chicken pox, and the herpes zoster virus can live in the body for years after the case of chicken pox is gone, and re-emerge as the painful blisters of shingles.

Can you get shingles in your private parts? ›

A person can get shingles on the genital area, but this is uncommon. Aside from blisters, genital shingles may also cause bladder and bowel problems. While shingles can cause genital lesions, other conditions, such as syphilis and genital herpes, can also have a similar presentation.

How can I live with herpes? ›

Brayer encourages the same safe practices for both oral and genital herpes: Don't share personal care items. During outbreaks, avoid infecting others. For genital herpes, forgo sex or use condoms from the first signs of an outbreak until the sores clear up. Also consider your communication options.

What medication can you take daily for herpes? ›

Treatment for Genital Herpes

Acyclovir: The oldest antiviral medication for herpes is acyclovir. It has been available since 1982 in a topical form (as an ointment) and sold since 1985 in pill form. Acyclovir has been shown to be safe in persons who have used it continuously (every day) for as long as 10 years.

What happens if herpes goes untreated? ›

Herpes can be painful, but it generally does not cause serious health problems like other STDs can. Without treatment, you might continue to have regular outbreaks, or they could only happen rarely. Some people naturally stop getting outbreaks after a while. Herpes typically does not get worse over time.

Can you pass herpes with no sores? ›

Yes. Even when no sores are present, the herpes virus is still active in the body and can spread to others. If you or your partner has herpes, reduce the risk of spread by: using a condom every time you have sex (vaginal, oral, or anal).

Is herpes Contagious all the time? ›

Both HSV-1 and HSV-2 are most contagious when sores are present, but can also be transmitted when no symptoms are felt or visible. For sexually active people, consistent and correct use of condoms is the best way to prevent genital herpes and other STIs.

Can a woman give a man herpes? ›

It's possible. You can spread genital herpes during oral sex even if you aren't showing any herpes symptoms at the time. But herpes is most contagious during an outbreak, when sores are open, moist, or leaking fluid.

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