|Scientists have found a human protein that blocks Zika replication and prevents cell death|
6 JUN 2016
Scientists have finally figured out what Zika virus does to the human body, and it explains why its effects can be so devastating, but infections can go for months without detection.
A new study has shown that not only does it go straight for the brain's progenitor cells, blocking around 20 percent of them from forming new neurons, but it does so without alerting the body’s immune system, so can go on replicating in the brain for weeks.
The good news is that, by better understanding how Zika is so successful in spreading throughout the human body, scientists from the University of Texas Medical Centre have found a way to combat it.
A tiny protein called interferon-induced protein 3 (IFITM3), which is naturally produced in the body, has been shown to reduce Zika’s ability to infect brain cells in both humans and mice, and can even prevent the cell die-off associated with the virus.
"This work represents the first look at how our cells defend themselves against Zika virus' attack," says one of the team, Abraham Brass. "Our results show that Zika virus has a weakness that we could potentially exploit to prevent or stop infection."
Since we all started talking about it back in January, the spread of Zika has been slow but steady, and we’re now looking at a total of 52 countries where infections have cropped up locally, including Brazil, Cuba, Papua New Guinea, and the Philippines.
Places like the US, the UK, and Australia have all reported cases from returning travellers, and the US just had its second confirmed birth of a baby infected by the virus.
That’s pretty devastating news, because scientists have finally found the biological mechanism that connects Zika to microcephaly - a rare and devastating neurological disorder that causes newborns to develop abnormally small skulls and brains. The World Health Organisation (WHO) officially confirmed in April that the virus is to blame for the skyrocketing number of birth defects in affected countries.
But now we might finally have an answer to the epidemic that’s been sweeping the Americas and the Pacific for at least 12 months now, and it’s been hiding in our bodies the whole time.
Brass and his team were investigating the activity of the IFITM3 protein in relation to emerging viral infections, because they found that people who have a genetic variant (or allele), of the IFITM3 gene are more susceptible to developing severe influenza. This variant appears to be fairly rare in people of European decent, but more common in Asia and Micronesia.
After working with the dengue virus, and other viruses that are related to Zika, the team found evidence that IFITM3 could block replication within healthy cells, so boosted levels of the protein within both mouse and human cells to see how a Zika infection would respond.
In both cases, the researchers found that boosted IFITM3 levels actually altered the cell membrane, toughening it up so the viruses struggled to break through. If cells had lower levels of IFITM3 than usual, the viruses were found to more easily break through the cells’ defences and replicate inside.
When human cells were exposed to Zika, they are overwhelming infected, as seen by the large number of green cells on the left. When IFITM3 levels were boosted, the same amount of virus was prevented from replicating (right panel). Credit: Brass Lab
"In effect, we see that IFITM3 allows our cells to swallow up and quarantine the virus thereby stopping their own infection, and also the infection of neighbouring cells," said one of the team, George Savidis. "We think this also reduces the levels of cell death caused by Zika virus."
"IFITM3 pretty much keeps Zika virus stuck in no man's land, where it can't do anything to harm us," he added.
So where to from here? The effects of the protein have only been tested in cells extracted from humans and mice and cultured in the lab, so will need to be tested in situ before we can get too excited about the potential of a new treatment or vaccine for Zika.
The team plans to test their findings in mice that are IFITM3-deficient to see if they’re more susceptible to the effects of the virus. They’ll also be searching for molecules that could boost the levels of IFITM3 in the body, which could be developed into a new drug that not only combats Zika, but many other related viruses. Right now, there is no treatment, cure, or prevention for Zika.
"A lot of data by us and others in the field has shown that IFITM3 has a big impact on blocking many emerging viruses such as dengue, Zika, and Ebola," says Brass. "Given our recent results with Zika virus, it's now even more important that we work to find out how IFITM3 is blocking these viruses, and use that knowledge to prevent and treat infections."
The results have been published in Cell Reports.