New research provides insights into what encourages the progression of the herpes virus.
According to the latest statistics from the Centers for Disease Control and Prevention (CDC), in 2015–2016, almost 48% of people in the United States were living with herpes simplex 1, a viral strain that causes oral infections.
Worldwide, 80% of the population has the virus. Once a person contracts it, the virus never goes away — it remains dormant in their body throughout their life.
Although herpes symptoms sometimes go unnoticed, for some people, they can be unpleasant and painful.
The herpes virus is also highly contagious, as a person can pass it on even when they do not have any symptoms.
New research suggests that contracting the virus may soon be preventable, as scientists offer new insights into what goes on at a cellular level during a herpes infection and find a way to slow the progression of the infection.
Emanuel Wyler, Ph.D., and Vedran Franke, Ph.D., from the Berlin Institute for Medical Systems Biology, in Germany, are the co-lead authors of the new paper, which appears in the journalNature Communications.
Importance of NRF2 transcription factor
The scientists developed an algorithm that enabled them to predict how an infection will progress in individual cells.
The researchers used single-cell RNA sequencing to analyze 12,000 human skin cells infected with herpes simplex virus 1 (HSV1). Single cell RNA sequencing is a revolutionary technique that allows for genetic expressions to be broken down at a much more granular level than bulk RNA sequencing.
The researchers explain the difference between single cell RNA sequencing and conventional, bulk RNA sequencing using an analogy of a smoothie.
“If I put ten types of fruit into a blender, I can roughly tell that the smoothie contains, say, blackberries when I taste it,” Wyler explains. “With single-cell RNA sequencing, we aren’t making a smoothie — we’re making a fruit salad. I can immediately identify the blackberries and say exactly how many are in the salad.”
The technique, combined with the algorithm, revealed to the researchers that a transcription factor called NRF2 plays a key role, with its activation inhibiting the progression of the infection.
Transcription factors are proteins that “decode” information from our genome and activate or deactivate specific genes by binding to certain DNA regions.
Franke explains how the new technique revealed the significance of the NRF2 transcription factor.
“I visualized changes in the regulation of each gene we investigated in a single cell,” he says. “This showed us that the activation level of the NRF2 transcription factor can be a marker for temporary resistance to HSV1 infection.”
The researchers also found that two NRF2 agonists, or activators, called bardoxolone methyl and sulforaphane impair the production of the virus, that is, they make the virus activate fewer of its own genes. This confirmed to the researchers the key role of NRF2.
Bardoxolone methyl is a drug designed to treat chronic kidney infection. It is currently in its third phase of clinical trials.
Finally, the study also revealed that the stage of the cell cycle also influences how vulnerable a cell is to HSV1 infection.
The researchers explain that the herpes virus is a good “general blueprint” for investigating cell states in viral infections, and they plan on using single cell RNA sequencing to study future viruses.