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1.
J Med Virol ; 2022.
Article in English | PubMed | ID: covidwho-2013653

ABSTRACT

The ongoing pandemic of severe acute respiratory coronavirus 2 (SARS-CoV-2) is causing a devastating impact on public health worldwide. However, details concerning the profound impact of SARS-CoV-2 on host cells remain elusive. Here, we investigated the effects of SARS-CoV-2-encoded viral proteins on the intracellular activity of long interspersed element 1 (L1) retrotransposons using well-established reporter systems. Several non-structural or accessory proteins (Nsps) of SARS-CoV-2 (i.e., Nsp1, Nsp3, Nsp5, and Nsp14) significantly suppress human L1 mobility, and these viral L1 inhibitors generate a complex network that modulates L1 transposition. Specifically, Nsp1 and Nsp14 inhibit the intracellular accumulation of L1 open reading frame proteins (ORF1p), whereas Nsp3, Nsp5, and Nsp14 repress the reverse transcriptase activity of L1 ORF2p. Given recent findings concerning the roles of L1 in antiviral immune activation and host genome instability, the anti-L1 activities mediated by SARS-CoV-2-encoded inhibitors suggest that SARS-CoV-2 employs different strategies to optimize the host genetic environment. This article is protected by copyright. All rights reserved.

2.
Journal of Biological Research (Italy) ; 94(2):82-83, 2021.
Article in English | Scopus | ID: covidwho-1674950

ABSTRACT

The COVID-19 pandemic has stimulated the production of different therapeutic approaches for the resolution of coronavirus infections. On one hand, nanobiomolecules have been proposed as bait material for viruses,1,2 on the other hand unconventional messenger RNA vaccines have been produced like SARS-CoV-2 mRNA vaccines (BioNTech/Pfizer BNT162b2 and Moderna mRNA-1273). A not negligible advantage of these mRNA-based vaccines is the speed with which they can be developed, especially in light of the discovery of new viral genetic variants and the need to adapt the vaccine to the rapid genetic changes of the virus. However, the biology of “retrotransposons” suggests greater caution in their large-scale use. The idea that the mRNAs of vaccines used to stimulate the immune response to SARS-CoV-2 are reluctant to integrate into the cellular genome needs more in-depth studies to be confirmd.3-9 In our opinion, these studies should take in consideration that the human genome con- © 2021 the Author(s), Licensee PAGEPress, Italy. All Rights Reserved.

3.
Cell Rep ; 36(7): 109530, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1330686

ABSTRACT

A recent study proposed that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hijacks the LINE-1 (L1) retrotransposition machinery to integrate into the DNA of infected cells. If confirmed, this finding could have significant clinical implications. Here, we apply deep (>50×) long-read Oxford Nanopore Technologies (ONT) sequencing to HEK293T cells infected with SARS-CoV-2 and do not find the virus integrated into the genome. By examining ONT data from separate HEK293T cultivars, we completely resolve 78 L1 insertions arising in vitro in the absence of L1 overexpression systems. ONT sequencing applied to hepatitis B virus (HBV)-positive liver cancer tissues located a single HBV insertion. These experiments demonstrate reliable resolution of retrotransposon and exogenous virus insertions by ONT sequencing. That we find no evidence of SARS-CoV-2 integration suggests that such events are, at most, extremely rare in vivo and therefore are unlikely to drive oncogenesis or explain post-recovery detection of the virus.


Subject(s)
COVID-19/virology , DNA, Viral/genetics , Genome, Human , SARS-CoV-2/genetics , Sequence Analysis, DNA , Virus Integration , Aged , Animals , COVID-19/diagnosis , Carcinoma, Hepatocellular/virology , Chlorocebus aethiops , HEK293 Cells , Hepatitis B virus/genetics , Host-Pathogen Interactions , Humans , Liver Neoplasms/virology , Long Interspersed Nucleotide Elements , Male , Nanopore Sequencing , Vero Cells
4.
Front Cell Infect Microbiol ; 11: 609160, 2021.
Article in English | MEDLINE | ID: covidwho-1140637

ABSTRACT

There is an increased global outbreak of diseases caused by coronaviruses affecting respiratory tracts of birds and mammals. Recent dangerous coronaviruses are MERS-CoV, SARS-CoV, and SARS-CoV-2, causing respiratory illness and even failure of several organs. However, profound impact of coronavirus on host cells remains elusive. In this study, we analyzed transcriptome of MERS-CoV, SARS-CoV, and SARS-CoV-2 infected human lung-derived cells, and observed that infection of these coronaviruses all induced increase of retrotransposon expression with upregulation of TET genes. Upregulation of retrotransposon was also observed in SARS-CoV-2 infected human intestinal organoids. Retrotransposon upregulation may lead to increased genome instability and enhanced expression of genes with readthrough from retrotransposons. Therefore, people with higher basal level of retrotransposon such as cancer patients and aged people may have increased risk of symptomatic infection. Additionally, we show evidence supporting long-term epigenetic inheritance of retrotransposon upregulation. We also observed chimeric transcripts of retrotransposon and SARS-CoV-2 RNA for potential human genome invasion of viral fragments, with the front and the rear part of SARS-CoV-2 genome being easier to form chimeric RNA. Thus, we suggest that primers and probes for nucleic acid detection should be designed in the middle of virus genome to identify live virus with higher probability. In summary, we propose our hypothesis that coronavirus invades human cells and interacts with retrotransposon, eliciting more severe symptoms in patients with underlying diseases. In the treatment of patients with coronavirus infection, it may be necessary to pay more attention to the potential harm contributed by retrotransposon dysregulation.


Subject(s)
Coronavirus Infections/virology , Coronavirus/genetics , Genome, Viral/genetics , Retroelements/genetics , Transcriptome , Cell Line, Tumor , Humans , Middle East Respiratory Syndrome Coronavirus/genetics , SARS Virus/genetics , SARS-CoV-2/genetics
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