Key Results & Achievements

The goals of this work package, to investigate the extent of and factors associated with sexual transmission of ZIKV in humans and animal models, were pursued over the four-year period.

Prof. Johan Neyts, University of Leuven"Besides the transmission via mosquitoes, Zika can also be vertically transmitted from mother to unborn child and via the sexual route. Here we will study in more detail both the vertical and sexual transmission route, to this end appropriate models will be used or newly established."

Prof. Johan Neyts, University of Leuven (KU Leuven)

Establishment of a model on sexual transmission in the ZIKV mouse model

Work Package 3 group leader, KU Leuven (KUL), established a mouse model to assess Zika virus replication in the testicles and to study the efficacy of antivirals on viral levels in this organ. If this proves efficacious, their potential antiviral effect could be further evaluated in vertical/sexual transmission models. This will be essential to the development of specific therapeutic interventions or prophylactic treatment to mitigate or even prevent severe complications of Zika infections.

Although an earlier study was unable to demonstrate vertical transmission of ZIKV in the KUL laboratories, publications have reported on vertical as well as sexual transmission using the same mouse species but a different ZIKV strain (a clinical isolate). Work was therefore undertaken with the University of Liège, GIGA- Neurosciences, Belgium, and an intra-placental ZIKV challenge mouse model was established.

Recruitment of male travelers returning from ZIKV endemic regions with ZIKV infection

ZIKV persistence in semen and its associated potential for sexual transmission caused great concern among people of child-bearing age who were exposed to ZIKV infection. The Institute of Tropical Medicine in Antwerp (ITG) conducted a prospective observational study in which travelers returning from endemic regions with confirmed ZIKV infection were recruited and sequential semen samples were collected for each case. Following the decline in overall ZIKV cases, the number of samples from travelers was lower than expected.

Results of the study showed that more than half of the ZIKV-infected men had prolonged shedding of ZIKV in the semen. The ZIKV isolates from semen (4 isolates) and serum (1 isolate) were sequenced and made available to other consortium members. A human cervix/sexual transmission model was developed using hysterectomy tissue and ex vivo challenge with semen derived ZIKV. This ex vivo model is important to assess the efficacy of potential therapeutic agents in blocking ZIKV entry into target cells.

A small selection of both more and less virulent ZIKV isolates will be evaluated in the intra-placental ZIKV challenge mouse model. The general condition of pups and dams as well as neuropathogenesis and possible effects on other organs will be assessed. This may provide further insight into the reported increase in microcephaly cases during the 2015–16 ZIKV epidemic. It will also provide a ‘tool’ to evaluate the potential antiviral effect of small molecule inhibitors and their potential (prophylactic) use. Ex vivo human tissue models will allow early human cellular targets of ZIKV upon sexual transmission to be identified and will establish ways for prophylaxis.

Participating Organisations

Group leader: Prof. Johan Neyts, University of Leuven (KU Leuven)

  • Institute of Tropical Medicine in Antwerp
  • Schweizerisches Tropen- und Public Health-Institut