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Virol J. 2017 Aug 22;14(1):161. doi: 10.1186/s12985-017-0828-z.

New insights into HCV replication in original cells from Aedes mosquitoes.

Author information

1
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, 71 Avenue des Martyrs, 38000, Grenoble, France.
2
Institut de Biologie et de Pathologie (IBP), Centre Hospitalier Universitaire (CHU) Grenoble-Alpes, CS10217, 38043, Grenoble Cedex 9, France.
3
Laboratoire Techniques de l'Ingénierie Médicale et de la Complexité, UMR CNRS 5525, Université Grenoble-Alpes, Grenoble, France.
4
Present Address: Dan L Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA.
5
EMBL Grenoble, 71 Avenue des Martyrs, CS90181, 38042, Grenoble Cedex 9, France.
6
The School of Biochemistry, University of Bristol, University Walk, Bristol, Clifton, BS8 1TD, UK. imre.berger@bristol.ac.uk.
7
Centre de Recherche en Cancérologie de Lyon (CRCL), UMR INSERM 1052/CNRS 5286, 151 Cours Albert Thomas, 69424, Lyon, Cedex 03, France. marie-anne.petit@inserm.fr.
8
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, 71 Avenue des Martyrs, 38000, Grenoble, France. emmanuel.drouet@ibs.fr.

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:

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

PMID:
28830495
PMCID:
PMC5567567
DOI:
10.1186/s12985-017-0828-z
[Indexed for MEDLINE]
Free PMC Article

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