Only 6-12% infected babies develop Congenital Zika Syndrome. Researchers worked on twins to find out why
Vulnerability to the dreaded Zika virus may have genetic elements to it, according to studies on twins published in Nature Communications.
The researchers, lead by Dr Mayana Zatz and Maria Rita Passos-Bueno – geneticists from the Human Genome and Stem Cell Research Center from the University of São Paulo (USP) -, also concluded that a single gene cannot explain the cases of Congenital Zika Syndrome (CZS) development nor the brain resistance to Zika virus. About 6% to 12% of the babies born from mothers infected with the Zika virus during pregnancy will have the CZS. It is yet to be explained why not all of them develop the syndrome. This study shed lights on the genetic components associated to it.
“If the baby has these genetic susceptibility factors, we believe he will not have microcephaly unless he is infected by the Zika virus. Maybe we can identify these people and prioritize them in a future vaccine strategy,” says Dr. Mayana Zatz.
Zika is spread mostly by the bite of an infected Aedes species mosquito (Ae. aegypti and Ae. albopictus). These mosquitoes bite during the day and night. Zika can be passed from a pregnant woman to her fetus. Infection during pregnancy can cause certain birth defects. There is no vaccine or medicine for Zika. Babies infected with Zika are born with smaller sized skulls (microcephaly) and also mental deficiencies.
“If the baby has these genetic susceptibility factors, we believe he will not have microcephaly unless he is infected by the Zika virus. Maybe we can identify these people and prioritize them in a future vaccine strategy,” says Dr. Mayana Zatz. Twins provide unique information to answer whether a certain condition has an environmental or a genetic cause. If genetic factors are determinant of a congenital disease, there must be more concordance between the pair of identical (monozygotic) twin babies than between the non-identical or dizygotic twins. Identical siblings should be more often both affected, than dizygotic twins that will be more likely “discordant” (one affected and one non-affected).
If the environment leads to the condition, the pattern observed in the two siblings of non-identical will be the same as observed in identical twins. It means that either none of the siblings will be affected, or both, or just one of them, independently of being monozygotic or dizygotic.
The study started in 2016, during Zika epidemics in Brazil. Mayana Zatz and her team looked for twins in which at least one baby had microcephaly. They accomplished to get in touch with families from 9 pairs of twins from 6 Brazilian states. Two pairs were identical twins, with both affected; one pair was non-identical but also had both affected; and 6 pairs were non-identical and discordant – one affected and one unaffected. This first scenario contributed to the hypothesis of genetic influence on Zika infection during fetal development.
In order to identify this possible genetic component, the team analyzed all the gene sequence from 8 pairs of twins and 10 other babies that developed the Zika syndrome as compared to normal controls. The exome analysis did not identify one gene variation capable of determining, alone, the susceptibility to the infection – instead, it excluded this possibility. The RNA sequencing came next. It allows scientists to measure gene expression – which genes are silenced or which are activated and sending messages to produce proteins in the cell. This is different from the previous DNA sequencing,that shows how genes are but not how they express themselves.
In conclusion, the results indicate that the development of the Zika syndrome in babies is not aleatory, it depends on neural progenitor cells’ susceptibility. It is possibly related to variants in several genes or to mechanisms that control gene expression and protein production.