Imagine that you are able to look at the six layers of cortex in a newborn who w
ID: 3511926 • Letter: I
Question
Imagine that you are able to look at the six layers of cortex in a newborn who was infected with the Zika virus in utero. The three deep layers of cortex appear normal, but the three most superficial layers of cortex have less neurons than you would typically see. (a) Based on what you know about Zika, explain why has this occurred (describe the particular cells involved as well as the steps of natural cell death). (b) What does this finding reveal about the timing of the Zika infection? (c) If the newborn is a monozygotic (identical) twin, will you see the same brain abnormalities in the twin? What if the twin is a dizygotic (fraternal) twin?
Explanation / Answer
Zika virus (ZIKV) is a member of the virusfamily Flaviviridae. It is spread by daytime-active Aedes mosquitoes, such as A. aegyptiand A. albopictus. Its name comes from the Ziika Forest of Uganda, where the virus was first isolated in 1947. Zika can spread from a pregnant woman to her baby. This can result in microcephaly, severe brain malformations, and other birth defects. The virus appears to preferentially kill developing brain cells. The virus readily infects neural stem cells which are the precursors of neurons and other brain cells, it was seen when they were grown on cell culture plates or coaxed to form 3D minibrains called cerebral organoids.
To gauge the virus’s possible effects on the developing brain, researchers at Johns Hopkins University in Baltimore, Maryland, and Florida State University in Tallahassee used induced pluripotent stem (iPS) cells to grow, in lab dishes, immature brain cells called human cortical neural progenitor cells. (iPS cells are adult cells that have been reprogrammed into stem cells that can grow into most of the tissues in the body.) They then exposed the neural progenitor cells to a lab strain of Zika virus.The virus readily infected the neural stem cells, neuroscientists Hongjun Song and Guo-li Ming, virologist Hengli Tang, and their colleagues reported Cell Stem Cell. Three days after the virus was applied, 85% of the cells in the culture dishes were infected. In contrast, when the virus was applied to cultures of fetal kidney cells, embryonic stem cells, and undifferentiated iPS cells, it infected fewer than 10% of the cells by day 3. Immature neurons derived from the neural progenitor cells were also less susceptible to the virus; 3 days after receiving a dose of the virus, fewer than 20% of those cells were infected.
The researchers noticed that the infected progenitor cells were not killed right away. Instead, the virus “hijacked the cells,” using the cellular machinery to replicate themselves, Song says. That helped the virus to spread quickly through the cell population, he says. His team also reports that infected cells grew more slowly and had interrupted cell division cycles, which could also contribute to microcephaly.
In a separate set of experiments, other researchers found that the virus can hamper the growth of another type of neural stem cell. In a preprint posted online on 2 March, neuroscientist Patricia Garcez and stem cell researcher Stevens Rehen at the D'Or Institute for Research and Education in Rio de Janiero, Brazil, report growing human iPS cells into clusters of neural stem cells called neurospheres, as well as into 3D organoids that in some ways resemble a miniature version of the human brain. When they infected the growing cells with Zika virus isolated from a Brazilian patient, the virus quickly killed most of the neurospheres and left the few survivors small and misshapen. Infected organoids grew to less than half their normal size.
Lancaster says the results echo earlier studies of gene mutations that cause microcephaly, which also affect neural progenitor cells. “You have two very different causes of microcephaly, but you see something very similar happening: a depletion of neural stem cells, and that would lead to fewer neurons” in the developing brain, she says. This was the study carried out on Zika virus and it's infection and published on the given link. It's gives a fruitful insight to the Zika virus and it's mode of infection. http://www.sciencemag.org/news/2016/03/zika-virus-kills-developing
Even the zygote is monozygotic or dizygotic, if the virus has entered the body of pregnant mother it will infect the both.