Enterovirus Infection Restricts Long Interspersed Element 1 Retrotransposition.

Yan Li,Haoran Guo,Wei Wei,Lili Zhang,Zhe Zhang,Qingran Yang,Yanhang Gao,Junqi Niu,Siyu Shen

doi:10.3389/fmicb.2021.706241

Yan Li, Haoran Guo + Show 7 more

Open Access

https://doi.org/10.3389/fmicb.2021.706241

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Abstract

Long interspersed element 1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome that can serve as an endogenous upstream activator of cytoplasmic nucleic acid sensing pathways to elicit an antiviral immune response. In this study, we investigated the influence of enteroviral infection on L1 mobility. The results showed that infection with different enteroviruses, both EV-D68 and EV-A71, blocked L1 transposition. We screened diverse viral accessory proteins for L1 activity and identified EV-D68 2A, 3A, 3C, and EV-A71 ORF2p proteins as viral L1 inhibitors. EV-D68 2A suppressed L1 mobility by expression suppression of L1 proteins. Viral proteins 3A and 3C restricted ORF2p-mediated L1 reverse transcription in isolated L1 ribonucleoproteins. The newly identified enteroviral protein ORF2p inhibited the expression of L1 ORF1p. Altogether, our findings shed light on the strict modulation of L1 retrotransposons during enterovirus replication.

Highlights

Transposable elements have been recognized as major contributors to mammalian genomes since the discovery of mobile DNA (O’Donnell and Burns, 2010)
We used a well-established EGFP reporter system in HEK293T cells to evaluate the effect of enterovirus infection on L1 retrotransposition (Moran et al, 1996; Ostertag et al, 2000; Goodier et al, 2012)
We investigated the role of EV-A71 infection in L1 mobility and showed that two EV-A71 (Anhui2007, CC063) strains strongly suppressed the EGFP-based L1 retrotransposition activity compared with that by control (Figures 1E–F and Supplementary Figures 1D,E)

Summary

INTRODUCTION

Transposable elements have been recognized as major contributors to mammalian genomes since the discovery of mobile DNA (O’Donnell and Burns, 2010). They are categorized into retrotransposons and DNA transposons. Enterovirus Suppresses LINE-1 Mobility (Kazazian and Moran, 1998; Goodier, 2016). This process is followed by integration events, such as non-homologous endjoining repair (Suzuki et al, 2009). A series of enteroviral proteins target diverse components of nucleic acid-sensing pathways to suppress host immune activation (Xiang et al, 2014, 2016; Rui et al, 2017). In the present study, we investigated the cross-talk between enterovirus and L1

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