They say the difference between herpes and love is that herpes lasts forever. But new research hints at a way to chase the virus from its hiding place and get rid of it for good.
Unlike viruses such as HIV or smallpox that slay nearly every cell they encounter, herpes simplex virus-1 (HSV-1) – the cause of cold sores – is a docile beast. When we’re healthy, HSV-1 snoozes inside our neurons, secluded from drugs and the immune system, where it switches on a single gene called LAT.
When we catch a cold, because the virus can’t distinguish between a mild cold and a deadly fever, the virus flees to the body’s surface, where it infects and kills epithelial cells. “It’s sort of like rats leaving a sinking ship,” says Bryan Cullen, a virologist at Duke University in Durham, North Carolina.
Now, by finding clues to how LAT works, Cullen’s team may have found a way to force the virus out of dormancy and onto the skin’s surface, where it’s easier to fight.
Hiding behind mRNA
Researchers suspected that LAT was the key to herpes’ ability to remain dormant inside nerve cells, but no-one knew how it did this. These nerve cells transcribe LAT into messenger RNA (mRNA), but while mRNA can usually be translated into a protein, mRNA from LAT doesn’t code for a protein and the cells usually just chew the mRNA to bits.
To determine the mysterious molecule’s job, Cullen’s team infected mice with HSV-1, and waited for the virus to retreat to nerve cells and go silent. Next, the researchers scoured the cells for traces of sliced RNA that matched that from LAT. Several hits turned out to be microRNAs, a recently-discovered kind of molecule that cells use to dial down the levels of proteins.
Four microRNAs came from cut-up LAT, while the fifth came from a previously unknown chunk of RNA, which suggests LAT isn’t the only viral DNA molecule involved in latency.
Many microRNAs play a role in maladies such as cancer and heart disease, and some viruses even make microRNAs to stymie cell defences.
But in a twist, HSV-1’s microRNAs latch onto viral mRNA molecules, preventing them from being used as templates for proteins. As a result, the cells are prevented from cranking out two virus proteins (ICP0 and ICP4) essential for escaping dormancy, Cullen’s team found.
It may be possible to coax viruses out of hiding by blocking these microRNAs, and then treating patients with drugs that stamp out herpes in epithelial cells, such as acyclovir. “Every virus that pops out gets killed,” Cullen says.
But this approach could prove troublesome because waking a virus seems to sacrifice the infected nerve cell, says virologist Patricia Spear, of Northwestern University in Evanston, Illinois. “You would be inducing replication of virus in the neuron and the question is how many neurons you want to kill off,” she says.
Journal reference: Nature, DOI: 10.1038/nature07103
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