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Zika virus infects human neural stem cells, but…

zika virus

The Zika virus infects a type of neural stem cell that gives rise to the brain’s cerebral cortex, Johns Hopkins and Florida State researchers have found. On laboratory dishes, these stem cells were found to be havens for viral reproduction, resulting in cell death and/or disruption of cell growth. While this study does not prove the direct link between Zika and microcephaly, it does pinpoint where the virus may be doing the most damage.

The researchers worked around the clock for a month to conduct the study, which provides a new platform to learn about the Zika virus using neuronal cells derived from human induced pluripotent stem cells. In the near future, the researchers hope to grow mini-brains from the stem cells to observe the long-term effects of Zika infection on neural tissue and to screen for potential therapeutics.

“This is a first step, and there’s a lot more that needs to be done,” says Hongjun Song, a neuroscientist and stem cell biologist.

“What we show is that the Zika virus infects neuronal cells in dish that are counterparts to those that form the cortex during human brain development.”

We still don’t know at all what is happening in the developing fetus. These findings may correlate with disrupted brain development, but direct evidence for a link between Zika virus and microcephaly is more likely to come from clinical studies.

As humans are typically infected by Zika virus carried by mosquitoes, the researchers also grew their Zika virus stock in mosquito cells for a few days before applying the virus onto the human cells used in all of their infection experiments.

One concerning discovery was that the stem cells that Zika was found to infect, called cortical neural precursors, become factories for viral replication. From a single infection, the virus particles spread through a plate of stem cells within a span of three days. There’s also no evidence that the cells are employing antiviral responses, which means we don’t know whether or how the virus is being cleared from the precursor cells.

“There are case reports for the Zika virus where they show that certain brain areas appear to have developed normally, but it is mostly the cortical structures that are missing,” says Guo-li Ming, a neuroscientist.

“So a very important question that emerges from our work is whether the Zika virus specifically targets the neural progenitor mostly responsible for generating the cortex.”

There are several other questions left to answer as well: why are the symptoms in adults so mild? How is the virus entering the nervous system of the developing fetus? Zika infects adults when mosquitoes deposit the virus on human skin, and our immune cells carry it into the blood. But how is the virus crossing the blood-brain barrier? And could Zika infect the small population of neural stem cells that adults keep above the brain stem in their hippocampus?

“We are trying to fill the knowledge gap between the infection and potential neurological defects,” says first author Hengli Tang, the team’s virologist whose lab studies RNA viruses like Zika, Dengue, and hepatitis C virus.

“The questions we address here are among the very first questions people want to know the answers of.”

 “We hope our results will help educate the public and government decision makers because they need to have more information on this virus, and we have to take it seriously,” Song says.

Now for the but… We’ve been silent on the zika virus, there is a good reason for this. Do you recall the avian flu epidemic that killed millions? Or how about the swine flu [H1N1]? We aren’t trying to downplay the importance of discovering what is causing microcephaly — or avian and swine flu — by any means. However, there is still only casual data suggesting a link and this is probably the strongest evidence yet to help support that link.

We aren’t saying there isn’t a connection by any means, at this point we would be surprised if another culprit was found. However, there is no need to panic as the instances of microcephaly while high — for microcephaly — overall instances of microcephaly are still quite low. In short, humanity has a way of catastrophizing things, then running wildly through the streets, without any real knowledge of what is going on.

Let’s put it this way, if you spend all your time and energy trying to hunt a tiger you suspect is hiding in the bushes, you might just miss the wolf that walked through your front door when you were busy in the bushes.

Tang, Hammack, Ogden, Wen, and Qian et al. (2016). Zika Virus Infects Human Cortical Neural Precursors and Attenuates Their Growth” Cell Stem Cell : dx.doi.org/10.1016/j.stem.2016.02.016

2 responses

  1. Has it been shown that Zika virus does, in fact, cross the blood-brain barrier? This study doesn’t show that, and I think it’s a critical question that must be looked into. If it doesn’t cross the BBB, this may explain why adults suffer only mild symptoms (another being that inflammatory responses are likely to be less severe in adults, generally). What about children infected with Zika? Do they also only show mild symptoms? Is brain development affected (unfortunately I think only long-term monitoring will demonstrate this, but if Zika doesn’t cross the BBB then they’re probably safe). The BBB is established during embryonic development, in a rostral-caudal wave that correlates with CNS development. It is in place in newborns though. The risk and severity of microcephaly may well correlate with how early the fetus is exposed to the virus, if it is shown that it can cross the BBB.


    March 6, 2016 at 7:00 am

    • Exactly, thank you. It’s important to understand the correlation with the zika virus, yes. However, it may be something completely unforeseen and the zika virus is just a coincidence. With the incidences of microcephaly so low and seemingly random when compared to zika infections it’s tough to say at the moment.


      March 6, 2016 at 12:35 pm

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