Work

Potential role of natural selection in a Dengue virus genotype replacement in New Caledonia

Year: 2020

Type: article

Abstract: Background: Dengue virus (DENV) is a mosquito–borne virus that represents a major public health problem worldwide. DENV genetic diversity encompasses four serotypes, each divided into several genotypes. DENV evolutionary dynamics are characterized by frequent DENV genotype replacements, which can be associated with changes in disease severity and human immunity. In 2012, a switch of DENV serotype 1 (DENV-1) genotype-I-Asia to genotype-IV-Pacific was associated with a massive outbreak (over 10,000 cases diagnosed) in New Caledonia. This outbreak and the prolonged circulation of DENV-1 from 2002 to 2018 was unusual. In this study, we hypothesized that this genotype switch reflected a higher replicative fitness of the genotype-I-Asia in the vector and/or in the human host. Methods and materials: For this purpose, we sequenced the full genome of 33 DENV-1 strains isolated from 2009 to 2016 to determine their genotype. Further, two strains per genotype isolated in 2012 during the co-circulation of both genotypes were selected for competition experiments. A 50:50 infectious ratio of the four viral combination was used for viral kinetics replication in vitro and in vivo. Human embryonic kidney 293 cells (HEK 293) were infected with each viral combination and replication of each DENV genotype was measured by RT-qPCR. Furthermore, field-derived Aedes aegypti were orally challenged with the same viral combinations to quantify viral infection and dissemination at 7 and 14 days post infection (dpi). Results: Replication kinetics performed in vitro showed a better replicative fitness for DENV-1 genotype I-Asia for two viral combinations. For in vivo studies, results showed a clear fitness advantage of DENV-1 genotype-I-Asia for three out of four viral combinations at both infection and dissemination steps (ranging from 64 to 100% of infected mosquitoes with only genotype-I-Asia detected), irrespective of the dpi and the DENV-1 genotype-I-Asia strain. Conclusion: To conclude, these results suggest that vector-driven selection may have contributed to the DENV-1 genotype replacement that occurred in 2012 in New Caledonia. At the beginning of the vaccine era, a better understanding of the evolutionary mechanisms driving DENV genotype replacements is crucial as these ones may have an impact on vaccine strategies by the complexity of their antigenic properties.

Source: International Journal of Infectious Diseases

DOI: 10.1016/j.ijid.2020.11.071