Zika fever: suspicions confirmed

Maxim Rousseau, Polit.roo

Computer model of the protein envelope (capsid) of the Zika virus
Manuel Almagro Rivas/Wikimedia Commons

After the Zika epidemic began in Brazil and other Latin American countries in 2015, doctors noticed a sharp increase in the number of cases of microcephaly in newborns. The connection between the disease and pathology in the development of the embryo seemed highly probable, but still only indirect evidence pointed to it. Now the effect of the Zika virus on the development of the embryo has been experimentally confirmed. Creating a model of the development of the disease in laboratory animals should also facilitate the search for a vaccine or other treatment methods.

The research results were published this week in three scientific journals at once: Cell, Cell Stem Cell and Nature. Scientists were able to demonstrate how the virus slows down the growth of the fetus in the uterus, causes brain damage and further death of the embryo. For the first time in laboratory animals, the connection of the virus with microcephaly was shown. If earlier a number of researchers suspected that the pathology could be caused by concomitant factors, for example, the use of insecticides, now it has become clear that the virus is able to cause it by itself.

Previously, scientists could not investigate the development of Zika virus fever in mice, since in their body the virus causes the release of interferons – substances that stimulate immune responses. In the laboratory of Michael Diamond from Washington University in St. Louis, they solved this problem by creating female mice in which the key interferon gene was disabled. In a parallel experiment, mice were used that received special antibodies against interferon. For the study, a culture of the Zika virus was used, obtained from people who had it during the epidemic in French Polynesia. Its genome is 99% the same as the virus that caused the current epidemic in South America. The experiments were carried out on pregnant females. Diamond and his colleagues reported on the results in the journal Cell.

The highest level of the virus in the blood was found in mice with the interferon gene disabled. Most of their embryos died. Scientists also found that the level of the virus in the placenta is a thousand times higher than in the blood of the body, which confirms the hypothesis of a particularly strong effect of the virus on the placenta, and through it – on the blood of the embryo. Mice injected with antibodies still retained enough interferon to control the infection and allow the offspring to survive. However, the newborn mice were small in size. In both groups of mice, accumulations of the virus in the heads of embryos were noted. Michael Diamond believes that the virus damages the embryo both directly and by affecting the placenta. In the latter case, there is a decrease in blood flow to the fetus. The results obtained by Diamond and his colleagues confirm the conclusions of previous studies conducted on cell cultures that the Zika virus infects and damages the progenitor cells of human nerve cells. Microcephaly was not detected in this experiment. Diamond suggests this was due to the fact that the researchers infected mice at a very early stage of pregnancy.

In two other studies, experiments ended with the development of microcephaly in mice. Their authors did not manipulate mice to make them more susceptible to the virus, but went the other way. Scientists from the Chinese Academy of Sciences, led by Zhiheng Xu, injected a strain of the virus isolated in the islands of Samoa directly into the brains of mouse embryos. The results of their experiment are published in the journal Cell Stem Cell. The journal Nature published an article by Brazilian scientists from the University of Sao Paulo. There, a group led by Fernanda Cugola used mice whose immunity was reduced for genetic reasons. They injected into the blood of mice a strain of the Zika virus obtained directly in Brazil.

Both studies revealed developmental disorders associated with microcephaly: thinning of the cerebral cortex and a decrease in its size. Also, in both cases, scientists confirmed that the virus infects progenitor cells of nervous tissue isolated from humans and mice.

At the moment, several experiments are being conducted simultaneously to demonstrate the development of Zika disease in pregnant monkeys, which can serve as a more accurate model of human disease. Due to the special importance of the study, authors from four US laboratories post the results on their websites without waiting for an official publication in a scientific journal. "We decided that for the benefit of the whole community, information should be available as widely as possible," says David O'Connor, whose group at the University of Wisconsin is most advanced in studying Zika virus infection in pregnant monkeys.

Now the university staff is monitoring the course of pregnancy in a female rhesus macaque who has been infected with the Zika virus. 50 days have passed, which is about half of the full gestation period, and the published ultrasound results show that the fetal head is relatively small. However, David O'Connor's staff say that so far the size of the head is not much different from the usual for rhesus monkeys. It will be possible to find out the result for sure only after a cesarean section, which will allow scientists to get a placenta (usually macaques eat it). As O'Connor notes, infected monkeys do not fully reflect the course of infection in humans, so the studies that are conducted on mice and monkeys complement each other.

Portal "Eternal youth" http://vechnayamolodost.ru  13.05.2016