Viral Fitness: Current Versus Historical ZIKV

Key Results & Achievements

The work package successfully obtained a valuable set of low-passage ZIKV strains representing the global viral diversity recently circulating 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 was utilized for an in-depth characterization of differences in transmissibility by mosquitoes and/or in pathogenicity in mouse models of disease. As a result, WP7 were able to perform the in-depth characterization of viral fitness both in mosquitoes in vivo and in mouse models of ZIKV infection and pathology. Findings from WP7 contribute to elucidate the evolutionary forces that may have driven ZIKV global emergence in the last decade and shed new light on ZIKV epidemiological patterns.

High transmissibility and pathogenicity of recent ZIKV strains from the African lineage

The global emergence of ZIKV since 2007 revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects such as microcephaly. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies was unclear.

WP7 found that recent African ZIKV strains largely outperformed their Asian counterparts in mosquito transmission kinetics experiments, which translated into a markedly higher epidemic potential in outbreak computer simulations. In addition, African ZIKV strains were significantly more lethal than Asian ZIKV strains in immunocompromised adult mice. Finally, prenatal infection of immunocompetent mouse embryos with an African ZIKV strain resulted in embryonic death whereas it caused microcephaly with Asian ZIKV strains. Together, these results demonstrate the high epidemic potential and pathogenicity of recent ZIKV strains from Africa. Importantly, they also imply that the African ZIKV lineage could more easily go unnoticed by public health surveillance systems than the Asian ZIKV lineage due to its propensity to cause fetal loss rather than birth defects.

Increased ZIKV susceptibility of Aedes aegypti populations outside their ancestral range

The main ZIKV vector is the mosquito Aedes aegypti, a species native to Africa that invaded most of the world’s tropical belt over the past four centuries. This geographical range expansion followed the evolution of a ‘domestic’ form of Ae. aegypti that specialized in biting humans and breeding in human water-storage containers. The consequences of this ecological shift for the mosquitoes’ ability to carry ZIKV were unknown.

To address this question, WP7 experimentally challenged 14 field-derived Ae. aegypti colonies from across the species range to their worldwide panel of ZIKV strains. Ae. aegypti populations from their ancestral range in sub-Saharan Africa were significantly less susceptible to ZIKV infection (regardless of the virus strain) than the globally invasive populations from tropical America and Asia. Among the African populations, ZIKV susceptibility was positively correlated with their proportion of ‘domestic’ genetic ancestry. Genetic analysis of a cross between African and non-African mosquitoes further identified genomic regions associated with differences in ZIKV susceptibility. Finally, mouse studies showed that African mosquitoes were substantially less likely to transmit ZIKV from a viremic host than their non-African counterparts. These results indicate that the recent evolution and range expansion of Ae. aegypti outside Africa was accompanied with a marked increase in ZIKV transmission potential. These results may contribute to explaining why Africa has been relatively spared from large-scale Zika outbreaks to date.

Participating Organisations

Group leader: Dr. Louis Lambrechts, Institut Pasteur

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