Understanding whether Zika virus emergence was associated with adaptive evolution will shed light on the evolutionary mechanisms underlying emergence. This will help to better predict unforeseen, future emergence events and thus enhance preparedness.

“Zika virus has been circulating in a silent manner in Africa and Asia for years. So the big question we need to answer is why the size and impact of the current epidemic? What differences between the virus then and now?”

Dr. Louis Lambrechts, Institut Pasteur

Unique Approach

The Viral Fitness group investigates evolutionary mechanisms underlying Zika virus emergence based on an experimental approach that is unique for at least two reasons:

  • it uses both live mosquitoes and mice, which are more relevant than cell lines to assess fitness differences,
  • it compares Zika virus strains that are more representative of wild-type viruses than reference strains, which have often been heavily passaged in cell culture.

Overall Objective

Researchers are investigating whether ZIKV emergence is associated with adaptive viral evolution in the vector, i.e., viral fitness differences that may explain the observed recent increase in ZIKV transmission by mosquitoes among humans. It also will address whether contemporary ZIKV results in more severe neurological disease, different tissue tropism and higher viral loads in mice compared with historic Zika virus isolates.

Specific Objectives

  • Investigate whether ZIKV emergence is associated with adaptive viral evolution in Aedes mosquitoes,
  • Determine viral fitness in vector competence assays of contemporary versus historical ZIKV isolates,
  • Investigate whether contemporary Zika viruses result in more severe neurological disease in mice compared with historical Zika virus isolates,
  • Investigate whether infection of mice with contemporary Zika viruses result in higher viremia levels in the testicles compared with historical Zika virus isolates,
  • Compare tissue tropism of contemporary ZIKV isolates versus historical isolates in mice.

Results and Achievements

  • The group has successfully obtained a valuable set of low-passage ZIKV isolates representing the recently circulating diversity of strains worldwide and spanning African strains, Asian pre-epidemic strains and Asian epidemic strains from the Pacific region and from Latin America. This biologically relevant set of ZIKV strains will allow in-depth characterization of viral fitness differences that may be associated with increased ZIKV transmission by mosquitoes and/or potential differences in virulence and pathological outcomes in a mouse model.
  • Pilot experiments have been conducted (susceptibility study in mosquitoes and virus tropism study in mice). A wild-type mosquito population from Colombia was also successfully colonized for subsequent laboratory studies.

Participating Organisations

Group leader: Dr. Louis Lambrechts, Institut Pasteur

  • University of Leuven (KU Leuven)
  • Fundación Universidad del Norte