PhD defence T. (Thomas) Langerak

Summary:

Zika virus (ZIKV) is a virus transmitted by mosquitoes and belongs to the virus family that also includes dengue virus (dengue fever), yellow fever virus and West Nile virus. ZIKV was first described in 1947 in the Zika forest in Uganda. Since then, very little research has been conducted on this virus because ZIKV infection in humans is often asymptomatic and therefore the virus was considered not clinically relevant. This view of ZIKV changed in late 2015 when it emerged that infection with ZIKV, which was now spreading rapidly in Brazil, could be associated with serious complications. One of these complications was Guillain-Barré syndrome (GBS). GBS is a disorder of the nervous system manifested by reversible, rapidly increasing muscle weakness, sometimes accompanied by loss of sensation or pain. Other complications of ZIKV first reported in Brazil in 2015 were congenital disorders in children whose mothers were infected with ZIKV during pregnancy. The most commonly reported congenital condition associated with ZIKV was microcephaly, a central nervous system abnormality that causes the head size to be too small. It is now clear that congenital ZIKV infection can cause a spectrum of congenital abnormalities such as disorders of the eye, microcephaly, increased muscle tone (hypertonia) and calcifications in the brain. All these abnormalities belong to congenital Zika syndrome.

The rapid spread of ZIKV in Central and South America, with the accompanying increasing incidence of GBS and congenital anomalies, led the World Health Organisation to declare the ZIKV outbreak a 'Public Health Emergency of International Concern' on 1 February 2016. Since then, much research has been conducted on ZIKV and significantly more knowledge has been gained about this virus and the complications it can cause. However, much is also still unknown about, among other things, the mechanisms behind the damage ZIKV can cause, the true extent of the ZIKV outbreak in 2015-2016 and how ZIKV can cross the placenta. This thesis describes research on the association between GBS and ZIKV, the epidemiology and antibody response after ZIKV infection and the role of cross-reacting antibodies on ZIKV infection during pregnancy and on ZIKV transmission across the placenta.