New insights into HCV replication in original cells from Aedes mosquitoes

Catherine Fallecker, Alban Caporossi, Yassine Rechoum, Frederic Garzoni, Sylvie Larrat, Olivier François, Pascal Fender, Patrice Morand, Imre Berger*, Marie Anne Petit, Emmanuel Drouet

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
226 Downloads (Pure)

Abstract

Background
The existing literature about HCV association with, and replication in mosquitoes is extremely poor. To fill this gap, we performed cellular investigations aimed at exploring (i) the capacity of HCV E1E2 glycoproteins to bind on Aedes mosquito cells and (ii) the ability of HCV serum particles (HCVsp) to replicate in these cell lines.

Methods
First, we used purified E1E2 expressing baculovirus-derived HCV pseudo particles (bacHCVpp) so we could investigate their association with mosquito cell lines from Aedes aegypti (Aag-2) and Aedes albopictus (C6/36). We initiated a series of infections of both mosquito cells (Ae aegypti and Ae albopictus) with the HCVsp (Lat strain - genotype 3) and we observed the evolution dynamics of viral populations within cells over the course of infection via next-generation sequencing (NGS) experiments.

Results
Our binding assays revealed bacHCVpp an association with the mosquito cells, at comparable levels obtained with human hepatocytes (HepaRG cells) used as a control. In our infection experiments, the HCV RNA (+) were detectable by RT-PCR in the cells between 21 and 28 days post-infection (p.i.). In human hepatocytes HepaRG and Ae aegypti insect cells, NGS experiments revealed an increase of global viral diversity with a selection for a quasi-species, suggesting a structuration of the population with elimination of deleterious mutations. The evolutionary pattern in Ae albopictus insect cells is different (stability of viral diversity and polymorphism).

Conclusions
These results demonstrate for the first time that natural HCV could really replicate within Aedes mosquitoes, a discovery which may have major consequences for public health as well as in vaccine development.

Keywords

Hepatitis C virus (HCV) HCV pseudo particles Aedes aegypti Aedes albopictus Human hepatocytes
Original languageEnglish
Article number161
Number of pages11
JournalVirology Journal
Volume14
DOIs
Publication statusPublished - 22 Aug 2017

Keywords

  • Hepatitis C virus (HCV)
  • HCV pseudo particles
  • Aedes aegypti
  • Aedes albopictus
  • Human hepatocytes

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