Thursday , August 5 2021

Zika: Find Out Why It Causes Microcephaly In Newborns

An international team in which Argentine researchers participated has elucidated one of the ways in which the virus triggers a congenital neurological syndrome Source: Archive – Credit: Reuters

One night in September 2015, Celina Turchi Martelli, a Brazilian epidemiologist from the School of Hygiene and Tropical Medicine in London, received a call from the Ministry of Health in her country: they detected that many babies with small heads were born and wanted to find out what was happening.

"I remember the first week I went to motherhood: my first feeling was that we were in the middle of a war, everyone had that strange look: the infectious doctors and the neuropediatricians, the nurses and the mothers … No one could understand the happened, "said Turchi Martelli
THE NATION during a visit to Buenos Aires.

The researcher, who would become head of the group tasked with testing the hypotheses about zika and microcephaly, was later included by the journal
Time among the most influential personalities on the planet and
Nature, Among the top ten scientists of 2016, he expressed in words the dramatic perplexity of the scientific community.

Then, the studies pointed to an association between the action of the virus and a set of neurological conditions that includes disturbances of the cerebral development, besides pathologies like Guillain-Barré syndrome, encephalitis, transverse myelitis and acute inflammatory demyelinating polyneuropathy, among others. . But one question remained: what are the biological gears that are driven to cause all these evils?

An international paper recently published in the journal
Cell phone and in which Argentine scientists participated, offers an answer: "We found one of the possible molecular pathways that explains how the Zika virus causes microcephaly," says Andrea Gamarnik, head of the Laboratory of Molecular Virology at Leloir Institute. (NS4A) disrupts the function of another human (Ankle 2) that had previously been identified as one of the causes of microcephaly in humans. "

Evidence indicates that NS4A, which participates in Zika replication, inhibits the functionality of Ankle2, which plays a key role in brain development.

The work was carried out by five centers in the United States with which Gamarnik and his team work as part of a program that began in 2010 to study how dengue interacts with human and mosquito cells.

New therapeutic targets

"Viruses are obligate intracellular parasites," explains the scientist, an internationally recognized virological name, "They have to use the cell to multiply." The program was born to identify all human proteins and mosquitoes and make large maps of their interactions with each of the ten that make up the dengue virus. "

The initiative has already shown encouraging results. Two years ago, Gamarnik and his team published
Pathogens Plos discovery of how a dengue protein interacts with
amendment (the process by which one gene can direct the synthesis of several different proteins) and thereby slows down the antiviral response of the cell so that the virus can replicate efficiently.

Since the dengue and zika viruses have small differences, when the latter appeared, the scientists considered that it was necessary to extrapolate all the information collected to create a new map.

"Zika and dengue differ in the form of transmission (the first can be transmitted sexually and vertically, from mother to child through the placenta)," says Gamarnik. "The pathology they cause is also very different: fever and, in severe cases, hemorrhage, but Zika can cause this terrible congenital syndrome that includes microcephaly and a group of neurological disorders in newborns.The other big difference is that zika persists in the semen of people infected for four or five months, while the other viruses in this group (such as dengue fever and yellow fever) last a few days in the blood, since two thirds of the infected patients do not present symptoms in the area where there is an outbreak, all have to take care of themselves. "

When the zika epidemic emerged in 2015, Priya Shah, a researcher at the University of California, San Francisco and the first author of the
Cell phone, took the initiative and requested the collaboration of Argentine scientists. Hugo Bellen, of Baylor College of Medicine, who was already working on Ankle2, was able to express Zika protein and found that it caused microcephaly in flies.

Once this mechanism has been clarified, it is not yet known what were the main differences between northern Brazil and other regions, such as Colombia, which also had a Zika epidemic, but fewer cases of microcephaly. "We still do not know what the explanation is, whether there is any genetic conditioning or whether cross-infection with both viruses may have influenced," concludes Gamarnik.

The epidemic

2015-2016. Northeast Brazil was the hardest hit area

As a result of the epidemic that shook the country for little more than twelve months, more than 3,000 children were born with the congenital zika syndrome. The most well-known manifestation of this condition is microcephaly, a disorder that causes insufficient skull development frequently associated with brain atrophy. Although the Zika and Dengue viruses are similar and both have ten proteins, scientists did not know what to attribute to differences in the pathologies they cause.

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