Publish Date: 19.02.2016

Category: News from the University

On 10 February 2016, the prestigious New England Journal of Medicine published a breakthrough article by the researchers of the Medical Faculty of the University of Ljubljana (Institute of Microbiology and Immunology and Institute of Pathology) and the University Medical Centre Ljubljana (Department of Perinatology, Division of Gynaecology and Obstetrics and Department of Radiology), which proves that the Zika virus carried by the mother can infect the foetal brain and cause terminal damage and microcephaly. Researchers had only suspected the link, and this study confirms the presence of the Zika virus in the brain of the foetus.

The research was headed by Tatjana Avšič Županc, PhD. The key members of the team were Jernej Mlakar, Miša Korva, PhD, Nataša Tul, MD, Mara Popović, MD, Mateja Poljšak Prijatelj, PhD, Jerica Mraz, Marko Kolenc, Katarina Resman Rus, Tina Vesnaver Vipotnik, Vesna Fabjan Vodušek, Alenka Vizjak, PhD, Jože Pižem. MD, PhD, and Miroslav Petrovec, MD, PhD.

Demonstration of viral particles and high viral load in the brain tissue sample, the absence of other possible disease causing agents and sequencing of the total viral RNA present the most compelling evidence that the congenital malformations of the central nervous system associated with the Zika virus infection during pregnancy are the result of the virus multiplying in the foetal brain.

The research is based on the case of a previously healthy European female who became pregnant while residing and working in Brazil. Towards the end of the first trimester of her pregnancy, she caught a fever accompanied by a rash. Ultrasonographic examination performed at 29 weeks of gestation showed the first signs of foetal anomalies, and the ultrasonography performed at 32 weeks of gestation confirmed foetal growth retardation, microcephaly and calcifications in the brain. The female requested termination of her pregnancy, which was approved by the Ethics Committee and the Pregnancy Termination Committee.

The autopsy of the foetus following the termination of the pregnancy confirmed severe structural damage of the brain (very little brain tissue, nearly complete absence of brain convolutions, hydrocephalus, calcifications), and microscopic examination revealed changes which are characteristic of viral infections. Electron microscopy revealed virus-like particles and particles resembling flavivirus replication complexes (which indicate multiplication of the virus in the brain).

Virological examinations with reversed transcriptase polymerase chain reaction (RT-PCR) confirmed the presence of Zika virus RNA and a relatively high viral load (large number of viral DNA copies per unit of tissue) in brain tissue samples. Numerous brain and other organ samples and tissue samples taken were tested for the presence of other flaviviruses (including the denga virus and yellow fever), other viruses (including the chikungunya virus, cytomegalovirus and herpes viruses) and other possible disease causing agents. The Zika virus was the only disease agent present, and it was discovered exclusively in the brain tissue samples. The presence of the virus was confirmed by determining the nucleotide sequence of the total viral DNA from the brain tissue, which was 99.7% compatible with the Zika virus strains discovered in French Polynesia in 2013 and in São Paolo, Brazil in 2015.