Researchers may have finally revealed the way that herpes is able to go into and come out of hiding.
A herpes simplex virus (HSV) infection lasts for life. No vaccination can prevent it, and no treatment can fully eradicate it.
The problem for doctors is that, most of the time, herpes lies dormant in nerve cells and becomes treatable only during unpredictable periods of activity.
Now, researchers — many from Cornell University’s Baker Institute for Animal Health, in Ithaca, NY — may have discovered what allows the genes in HSV to sometimes turn on.
The researchers have found that herpes’ viral DNA sometimes escapes suppressive protein wrappings in nerve cells and becomes reactivated.
Luis M. Schang, Ph.D., the senior author of the summary of these findings, explains that herpes’ on-again-off-again nature is “why antivirals cannot cure the infection and why, so far, it’s been impossible to develop a vaccine.” He points out that “Latency and reactivation are a major focus for herpes virus research.”
The team’s findings may provide the key to more successful HSV research and treatment. A summary of their work appears in PLOS Pathogens.
The World Health Organization (WHO) estimate that
People who have herpes may not realize it, since a herpes infection is asymptomatic when it is dormant, or latent. When an infection is active, either form is contagious.
HSV-1 is transmitted primarily through oral-to-oral or oral-to-genital contact, as well as through contact with the skin around the mouth, sores, or saliva of a person with an active infection. HSV-2 is spread through genital-to-genital contact.
Herpes in its active, or lytic, stage can produce painful ulcers — open sores — and blisters around the mouth, genitals, and anus.
“Any problem that herpes causes is because of reactivation from latency,” says Schang, adding that “Latency and gene regulation is a big problem because we do not know nearly enough about it.”
In addition, among people with compromised immune systems, the symptoms of herpes infection may be more severe and frequent.
Previous research has investigated the mechanisms that allow individual herpes genes to switch on and off.
Schang’s team has discovered, however, that the issue may not involve individual herpes genes but the entire herpes genome becoming activated, allowing individual genes to be expressed. The paper reveals how this may occur.
Unfurled, the DNA inside a single cell would be about 1 yard long, while nerve cells are only roughly a hundredth of a millimeter in diameter.
Upon invasion by HSV, a nerve cell responds by wrapping the viral DNA very tightly around histones, proteins shaped like tiny spools, which are then packed inside chromatin fibers.
Thus imprisoned in chromatin, the virus becomes dormant. However, sometimes nerve cells fail to wrap herpes’ DNA tightly enough, leaving some of it exposed to the cells’ chemistry.
When this occurs, the exposed DNA can reactivate, and the virus’ individual genes can initiate lytic infections that produce herpes symptoms.
With this insight from Schang and colleagues, researchers may be able to delve deeper into why, when, and how this tight bundling can become undone, unlocking at least one of the secrets of this implacable infection.