Profile of Small RNAs, vDNA Forms and Viral Integrations in Late Chikungunya Virus Infection of Aedes albopictus Mosquitoes.

Michele Marconcini,Mariangela Bonizzoni,Umberto Palatini,Nabor Lozada-Chávez,Vincent Houé,Elisa Pischedda,Davide Sogliani,Anna-Bella Failloux

doi:10.3390/v13040553

Michele Marconcini, Mariangela Bonizzoni + Show 6 more

Open Access

https://doi.org/10.3390/v13040553

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Abstract

The Asian tiger mosquito Aedes albopictus is contributing to the (re)-emergence of Chikungunya virus (CHIKV). To gain insights into the molecular underpinning of viral persistence, which renders a mosquito a life-long vector, we coupled small RNA and whole genome sequencing approaches on carcasses and ovaries of mosquitoes sampled 14 days post CHIKV infection and investigated the profile of small RNAs and the presence of vDNA fragments. Since Aedes genomes harbor nonretroviral Endogenous Viral Elements (nrEVEs) which confers tolerance to cognate viral infections in ovaries, we also tested whether nrEVEs are formed after CHIKV infection. We show that while small interfering (si)RNAs are evenly distributed along the full viral genome, PIWI-interacting (pi)RNAs mostly arise from a ~1000 bp window, from which a unique vDNA fragment is identified. CHIKV infection does not result in the formation of new nrEVEs, but piRNAs derived from existing nrEVEs correlate with differential expression of an endogenous transcript. These results demonstrate that all three RNAi pathways contribute to the homeostasis during the late stage of CHIKV infection, but in different ways, ranging from directly targeting the viral sequence to regulating the expression of mosquito transcripts and expand the role of nrEVEs beyond immunity against cognate viruses.

Highlights

Chikungunya virus (CHIKV) was first isolated in Tanzania in 1952 [1] causing sporadic outbreaks
We show that CHIKV infection does not result in new nonretroviral Endogenous Viral Elements (nrEVEs) formation, but the differential accumulation of PIWI- interacting RNAs (piRNAs) derived from existing nrEVEs correlates with differential expression of an endogenous transcript
We describe the profile of small RNAs and the presence of vDNA forms and nrEVEs during persistent infection of Ae. albopictus with CHIKV

Summary

Introduction

Chikungunya virus (CHIKV) was first isolated in Tanzania in 1952 [1] causing sporadic outbreaks. The increasing public heath significance of CHIKV is tightly linked with the global invasion of Asian tiger mosquito Aedes albopictus which established in temperate areas of the world [6]. In response to this trend, chikungunya was included in the WHO list of the most relevant neglected tropical diseases in 2017 [7]. Viruses are blocked in the midgut (i.e., midgut infection barrier) or cannot disseminate from the midgut (midgut escape barrier) or the salivary glands (salivary glands barrier) [14,15] These infection-refractory phenotypes are both viral species and mosquito strain/species specific [16,17,18,19]. It was recently proposed that unravelling the molecular underpinning of viral persistence could facilitate the design of population replacement strategies of mosquito control which avoid emergence of viral resistance [24]

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