lthough not a concrete link to microcephaly, study shows that Zika can infect cells similar to those involved in brain development and disrupt cell growth.
Scientists examining the link between the Zika virus and microcephaly in babies have discovered that the virus can infect cells similar to those involved in brain development.
Published in Stem Cell Stem the study, led by scientists at Johns Hopkins University and Florida State University, reveals that when lab-grown neuronal cells are exposed to the Zika virus, it infects the cells and is able to produce a large number of copies of itself. The researchers also found that the virus was able to disrupt pathways within the cells and limit their growth.
However, the scientists are quick to point out that their results do not prove that the mosquito-borne virus is leading to abnormal brain development of babies in the womb. “We don’t have the direct evidence to show that this will link the Zika virus to microcephaly,” said Dr Zhexing Wen, a co-author of the paper from Johns Hopkins University.
In order to probe the effect of the virus on neuronal cells, the scientists took human skin cells and “reprogrammed” them into pluripotent stem cells, which were then encouraged to grow into cells known as human cortical neural progenitor cells (human NPCs). These cells are similar to those that lead to the development of the cortex - the region of the brain that is typically underdeveloped in babies born with microcephaly.
The cells were then exposed to Zika virus. After 56 hours 65- 90% of the cells were infected with Zika; the virus was also found to be able to reproduce in large numbers within infected cells. What’s more, the Zika virus was found to interfere with cell processes and to increase cell death.
“This study hasn’t directly proved that the Zika virus causes microcephaly,” said Wen. “But it is telling that the human NPCs are very susceptible to the Zika virus and the Zika virus can cause the disruption of the human NPC growth and this may potentially correlate to the disrupted brain development in the foetus.”
While the Zika virus has previously been found to infect a range of human cells types, the latest study reveals that human NPCs showed a greater susceptibility to infection than some other cell types, including human embryonic stem cells. “We also want to know why the human NPCs are quite specific for the infection,” Wen adds.
There are, however, many more questions. “Maybe different strains of the Zika virus have different effects or maybe different people in different areas of the world may have a different response to the same Zika virus,” says Wen. But he believes the technique used by the team could help to provide answers. “We can test this out with the human NPC system,” he says.
Wen adds the team now want to use the human NPC system to screen for drugs that could prevent or eradicate infection by the Zika virus.
Responding to the paper, Prof Jonathan Ball from the University of Nottingham urges caution in interpreting the study’s findings. “There are still a number of unknowns,” he says. “It isn’t clear if the virus growing in the laboratory in these artificially generated nerve cells behaves the same way as it would in a human. We are complex organisms and lots of factors can affect how a virus infection pans out.”
However, he does believe the findings are a step towards probing the impact of Zika on the human body. “These are really interesting findings and go some way to understand how Zika virus might be causing the serious conditions that it is associated with,” he adds. “But we must remember, at the moment Zika and the link to microcephaly and Guillain-Barré [a neurological condition that can cause temporary paralysis] are only associations, and we need to know what is really happening in natural infection. Unfortunately we don’t have all of the tools to be able to do this work and the necessary experiments are tricky to do.”
Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, believes such in vitro research builds on a range of studies exploring the link between the Zika virus and microcephaly. “It’s all accumulating complementary evidence,” he says.
“It is important to understand and definitively prove - or not - the direct causal relationship between infections during pregnancy and microcephaly. As the weeks and months go by there is more and more evidence that is becoming almost compelling that there is a direct causal link,” he told the Guardian.
“I think it is reasonable to make the assumption that sooner or later we will find definitive proof that Zika is related to microcephaly,” he adds. “Then we have a compelling need to protect pregnant women and women of childbearing age who will become pregnant.”
While there is currently no vaccine available to combat the virus, Fauci says that several are under development, with phase one trials for the first vaccine scheduled to begin towards the end of the summer. “Barring any unforeseen glitches I would think we would start that in September,” he says. “By the end of 2016, early 2017 we will know if it is safe in normal people.”
However finding out if it works could take time. “Everything is going to depend on the state of the epidemic because if [it] dies down it might take a couple of years to show that the vaccine works,” says Fauci. “If the epidemic is raging as it is now in early 2017, we may actually know whether it works by the end of 2017.”
