The Brazilian Zika virus strain (ZIKVBR) can pass through the placenta of mice and cause developmental defects including microcephaly. The results of these studies were recently published in the journal Nature, which is the first animal experiment model to prove that the Brazilian Zika virus strain causes birth defects. The paper also found that the Brazilian Zika virus can infect human brain organoids cultured in vitro, induce cell death and destroy the layer of neural tissue called the cortex.
The recent increase in the number of deformed babies born in Brazil is believed to be related to the outbreak of a strain of Zika virus originating in Asia. The virus is transmitted through Aedes aegypti, and infant deformities include small heads and other neurological diseases. However, there has been a lack of animal models that prove that the Brazilian Zika virus strain causes birth defects. Alysson Muotri, University of California, San Diego, Patricia Beltro Braga, Jean Pierre Peron, University of São Paulo, Brazil, and the team used the Brazilian Zika virus strain isolated from a clinical case in northeastern Brazil to infect pregnant mice of two different strains (SJL and C57BL/6), conducted multiple experiments, each experiment used 2-6 mice. When the pups were born, the researchers immediately evaluated the newborn mice and found that the pups born from pregnant female mice of the SJL strain infected with the Brazilian Zika virus showed obvious signs of systemic growth retardation, also called intrauterine growth. Restricted and showed signs of microcephaly, such as malformations of cerebral cortex, compared with the control group. In contrast, the pups of C57BL/6 female mice infected with Brazilian Zika virus did not show any significant difference compared with the control group, which may be related to the strong antiviral immune response of mice of this strain.
Researchers also found that the Brazilian Zika virus can induce cell apoptosis in mouse nerve tissue, and it can also infect human brain organoids, trigger cell apoptosis and disrupt the cortex. The analysis results showed that the Brazilian Zika virus crossed the placenta and caused microcephaly by targeting cortical precursor cells to induce apoptosis and impair neurodevelopment.
These findings reinforce the existing evidence linking the Brazilian Zika virus outbreak with the increasing number of clinical cases of congenital malformations, and may help future preclinical research, including vaccine development.