Tag Archives: herpes

Return of the cold sore

Credit: Wikimedia Commons.

The herpes simplex virus represents a sore spot in more ways than one. Without a warning, a victim’s sores might flare up with no warning, triggered by factors as light as stress and exposure to UV light. Cold sores, also known as fever blisters, are one of the most common symptoms of herpes (HSV) reactivation.

Now, new research at least tells scientists what exactly goes on when the clinical Herpes simplex virus (HSV-1), one of the forms, reactivates. UVA Today notes that “the new insights help doctors better understand what is happening in neurons and the immune system,” and that could lead to ways to prevent unwanted outbreaks, the researchers hope.

What do we mean by one of its forms? According to the World Health Organization, herpes simplex virus-1 (HSV-1) is one of two herpes simplex virus germs. The other is herpes simplex virus type 2 (HSV-2). WHO draws an important distinction between the two.

“HSV-1 is mainly transmitted by oral-to-oral contact to cause oral herpes (which can include symptoms known as ‘cold sores’), but can also cause genital herpes. HSV-2 is a sexually transmitted infection that causes genital herpes. Both HSV-1 and HSV-2 infections are lifelong.”

Wait, lifelong?

Yep. According to UVA Today, the virus never really goes away. “Instead, it lurks inside neurons, waiting for the right moment to strike again, a process known as reactivation.”

In this recent effort, researchers found that when neurons harboring the virus were exposed to stimuli that induce “neuronal hyperexcitation,” the virus senses this particular change and seizes its opportunity to reactivate. In other words, when the neurons flare up, so too does the herpes.

Their investigation took place at the University of Virginia’s Department of Microbiology, Immunology, and Cancer Biology (MIC). They discussed their discovery in their paper “Neuronal hyperexcitability is a DLK-dependent trigger of herpes simplex virus reactivation that can be induced by IL-1” published in the journal eLife.

Unsurprisingly, scientists are eager to learn more about the virus: the numbers of those who have contracted it are significant. As the authors explained in their paper:

“Herpes simplex virus-1 (HSV-1) is a ubiquitous human pathogen that is present in approximately 40–90% of the population worldwide (Arvin, 2007). HSV-1 persists for life in the form of a latent infection in neurons, with intermittent episodes of reactivation.”

Interestingly, the virus hijacks an immune response in the body. Per UVA Today:

“In response to prolonged periods of inflammation or stress, the immune system releases a cytokine, Interleukin 1 beta.” This cytokine is in epithelial cells in the skin and eye and is released when these cells are damaged by ultraviolet light. The researchers discovered that “Interleukin 1 beta then increases excitability in the affected neurons, “setting the stage for HSV to flare up.”

Their model was developed using mouse neurons infected with HSV. The paper’s authors noted why this focus on reactivation matters:

“Reactivation from a latent infection and subsequent replication of the virus can cause substantial disease including oral and genital ulcers, herpes keratitis, and encephalitis. In addition, multiple studies have linked persistent HSV-1 infection to the progression of Alzheimer’s disease (Itzhaki, 2018).”

In the bigger picture, too, the research highlights how “some viruses have evolved to take advantage of what should be part of our infection-fighting machinery,” concluded Anna Cliffe, one of the researchers.

Spaceflight activates dormant viruses like herpes

You can now also add herpes to the list of many perils and challenges to human health that outer space poses. According to a new study, spaceflight weakens the immune system enough to reactivate dormant viruses such as the Epstein–Barr virus (EBV), varicella-zoster virus (VZV), and herpes-simplex-1 (HSV-1).

Credit: Public Domain.

Researchers at the Johnson Space Center found that spaceflight increases the secretion of stress hormones like cortisol and adrenaline, which are known to suppress the immune system. This way, viruses inside our bodies that are in a latent state (meaning they do not replicate) become reactivated because immune cells are no longer able to suppress or eliminate them.

“NASA astronauts endure weeks or even months exposed to microgravity and cosmic radiation—not to mention the extreme G forces of take-off and re-entry,” says senior author Dr. Satish K. Mehta of  Johnson Space Center. “This physical challenge is compounded by more familiar stressors like social separation, confinement and an altered sleep-wake cycle.”

Mehta and colleagues analyzed saliva, blood, and urine samples collected from astronauts before, both during and after spaceflight. Most people get oral herpes — or herpes simplex virus type 1 — by the age of 20. Following the first infection, usually after one or two weeks, the virus will become dormant in facial nerve tissues. The researchers found that about half of all astronauts aboard Space Shuttle and International Space Station had four of eight know herpes viruses in an activate state, although only six astronauts (a small proportion) developed symptoms. Other reactivated viruses include CMV and EBV, which are associated with different strains of mononucleosis or the “kissing disease”.

“To date, 47 out of 89 (53%) astronauts on short space shuttle flights, and 14 out of 23 (61%) on longer ISS missions shed herpes viruses in their saliva or urine samples,” reports Mehta. “These frequencies—as well as the quantity—of viral shedding are markedly higher than in samples from before or after flight, or from matched healthy controls.”

The researchers found that virus shedding was active in astronauts for up to 60 days after returning to Earth. Although only a few astronauts developed symptoms, continued virus shedding could endanger immunocompromised or uninfected contacts on Earth, like newborns.

This is just one of the many adverse effects caused by spaceflight. Previously, researchers found that prolonged exposure to a microgravity environment can result in tissue damage to the gastrointestinal tract, eyes, and brain. Mehta and colleagues suggest that targetted vaccine protocols for astronauts might offset some of the risks associated with virus reactivation.

“Trials of other herpes virus vaccines show little promise, so our present focus is on developing targeted treatment regimens for individuals suffering the consequences of viral reactivation,” Mehta said.

“This research has tremendous clinical relevance for patients on Earth too. Already, our spaceflight-developed technologies for rapid viral detection in saliva have been employed in clinics and hospitals around the world.

The findings appeared in the journal Frontiers in Microbiology

Modified herpes virus used to treat skin cancer

A new clinical trial from the UK brings exciting results as a modified strain of the herpes virus has been successfully used to treat skin cancer patients, with only minor side effects.

Image via Herpes Aware.

The trial run included 436 patients suffering from aggressive melanoma that signed up to be treated through virotherapy – the usage of genetically modified strains of viruses that attack specific pathogens or cells, such as malign cancer cells. Kevin Harrington, professor of biological cancer therapies at the Institute of Cancer Research London, who lead the research team, said: “This is the big promise of this treatment. It’s the first time a virotherapy has been shown to be successful in a phase 3 trial.”

Named Talimogene Laherparepvec (T-VEC), the drug was administered once every 14 days for up to 18 months, participants only showing flu-like side effects after the first few injections. One in four patients responded well to the treatment, 16% of them still being in remission six months later, compared to the 2% of the control group, treated using immunotherapy. 10% of those treated using the new drug had complete remission, showing no signs of cancer. During the trial, the T-VEC group patients survived an average of 41 months, while those in the control group survived an average of 21.5 months. These results are especially encouraging as some of the patients were in too severe condition to respond to conventional treatment :

“They had disease that ranged from dozens to hundreds of deposits of melanoma on a limb all the way to patients where cancer had spread to the lungs and liver,” said Harrington.

[Also Read: Modified cold sore virus shrinks melanoma tumors]

“Just gonna drop this off here real quick” – T-VEC virus. Image via Digital Deconstruction.

T-VEC works by taking away the virus’ ability to produce the protein that allows it to infect healthy cells. But malign cells produce the protein needed on their own, offering the virus the means to infect and thrive in cancerous tissue. As the herpes virus multiplies vigorously inside the cancer cells they burst open, spilling the virus into the surrounding area, triggering a secondary immune reaction against the tumour.

“We may normally think of viruses as the enemies of mankind, but it’s their very ability to specifically infect and kill human cells that can make them such promising cancer treatments. In this case we are harnessing the ability of an engineered virus to kill cancer cells and stimulate an immune response” said Professor Paul Workman, Chief Executive of The Institute of Cancer Research. And once the immune system gets the wake up call from T-VEC treatment, even secondary tumours that have not been infected by the virus have shrunk or disappeared completely. “It’s like an unmasking of the cancer,” said Harrington. “The patient’s immune system wakes up and attacks the cancer cells wherever they are in the body.”

Uninfected tumours attacked after T-VEC treatment.
Image via meetinglibrary.asco.org

The trial results are so promising that the research team hope to get it on the market by 2016. And successfully passing a phase 3 trial means that the pharmaceutical company Amgen only needs approval from the FDA and European Medicines Agency before they can make the treatment commercially available.

 

New infections cause dormant viruses to reactivate

Herpes viruses are almost impossible to eliminate from your body. While other viruses succumb when they are defeated by the immune system, the herpes virus remains in the body forever, lying in wait, sometimes reactivating years later. A new study has found that new infections may weaken the body just enough to favor the reawakening of herpes.

Herpes virus

Artistic representation of the herpes virus. Via Gofolic.

For quite a while, scientists have been trying to figure out exactly why the virus sometimes reactivates, even after lying dormant for decades. Herpes, which has been associated to cancer, could be combated with more efficiency if researchers understand the underlying mechanisms of the pathogen. Now, a team has found that interactions with other infections later in life are the catalysts for the awakening.

“Probably 95 percent of us have been infected with at least one herpes virus, but many people never have a problem with it,” said study co-author Rolf Renne, a professor of molecular genetics and microbiology in the UF College of Medicine and a member of the UF Genetics Institute and the UF Health Cancer Center. There are eight herpes viruses that infect humans, causing diseases that range from cold sores and chickenpox to mononucleosis and cancer. “The question has been: What happens to reactivate these viruses to cause disease?”

To me, this information was quite shocking. The fact that Renne, one of the leading voices in the field believes that almost all of us have been infected is quite worrying – especially when in the vast majority of the cases the virus is never truly eliminated from the body.

What they found in this research is that a protein called interferon gamma keeps herpes in check, which explains why the virus typically remains dormant in the body. But when the immune system is challenged, especially when fighting an infection,  another protein called interleukin 4 was released, which not only blocked interferon gamma from doing its job but also directly activated virus replication. Again, the big problem here is not the herpes virus in itself – but rather that when the virus reactivates, it infects new cells, and significantly increases the chances of a cancerous tumor developing.

“The fact that the virus can ‘sense’ the immune reaction to a worm and respond by reactivating is a remarkable example of co-evolution,” said senior author Dr. Herbert W. Virgin IV, of Washington University in St. Louis. “We think other interactions between multiple infectious agents and the immune system will be discovered over time that we will view as similarly sophisticated or maybe even devious. Understanding these interactions will help us survive in a complex microbial world.”

Their findings are quite intuitive – it seems rather safe to assume that the weakening of the body favors the reemergence of dormant virus, but intuitive is not science.

Source: University of Florida