Influence of Endogenous Viral Sequences on Gene Expression

Sofuku, Kozue; Honda, Takeshi

doi:10.5772/intechopen.71864

“…nrEVEs derived from the nucleoprotein (N) gene of bornaviruses, EBLNs, are present in the genomes of several mammalian species, including humans [147]. Homo sapiens EBLN-1 (hsEBLN-1) RNA potentially affects the expression of a neighboring COMMD3 gene [148,149]. Since COMMD proteins interact with different NF-κB subunits, hsEBLN-1 RNA may regulate immune responses through the COMMD3-NF-kB pathway [148].…”

Section: Non-retroviral Endogenous Viral Elements and Innate Immunitymentioning

confidence: 99%

Roles of Human Endogenous Retroviruses and Endogenous Virus-Like Elements in Cancer Development and Innate Immunity

Katoh,

Honda

2023

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Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections in the host genome. Although mutations and silencing mechanisms impair their original role in viral replication, HERVs are believed to play roles in various biological processes. Long interspersed nuclear elements (LINEs) are non-LTR retrotransposons that have a lifecycle resembling that of retroviruses. Although LINE expression is typically silenced in somatic cells, it also contributes to various biological processes. The aberrant expression of HERVs and LINEs is closely associated with the development of cancer and/or immunological diseases, suggesting that they are integrated into various pathways related to the diseases. HERVs/LINEs control gene expression depending on the context as promoter/enhancer elements. Some RNAs and proteins derived from HERVs/LINEs have oncogenic potential, whereas others stimulate innate immunity. Non-retroviral endogenous viral elements (nrEVEs) are a novel type of virus-like element in the genome. nrEVEs may also be involved in host immunity. This article provides a current understanding of how these elements impact cellular physiology in cancer development and innate immunity, and provides perspectives for future studies.

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“…The misclassification of EVE sequences as exogenous viruses is a particularly underestimated possibility in virus discovery studies based on (meta)-transcriptomics datasets. Indeed, depending on their integration sites, EVEs can exploit nearby regulatory elements and the host cell’s transcriptional machinery, facilitating EVE transcription ( Sofuku et al. 2018 ).…”

Section: Introductionmentioning

confidence: 99%

A tale of caution: How endogenous viral elements affect virus discovery in transcriptomic data

Brait,

Hackl,

Morel

et al. 2023

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Large-scale metagenomic and -transcriptomic studies have revolutionized our understanding of viral diversity and abundance. In contrast, endogenous viral elements (EVEs), remnants of viral sequences integrated into host genomes, have received limited attention in the context of virus discovery, especially in RNA-Seq data. EVEs resemble their original viruses, a challenge that makes distinguishing between active infections and integrated remnants difficult, affecting virus classification and biases downstream analyses. Here, we systematically assess the effects of EVEs on a prototypical virus discovery pipeline, evaluate their impact on data integrity and classification accuracy, and provide some recommendations for better practices. We examined EVEs and exogenous viral sequences linked to Orthomyxoviridae, a diverse family of negative-sense segmented RNA viruses, in 13 genomic and 538 transcriptomic datasets of Culicinae mosquitoes. Our analysis revealed a substantial number of viral sequences in transcriptomic datasets. However, a significant portion appeared not to be exogenous viruses but transcripts derived from EVEs. Distinguishing between transcribed EVEs or exogenous virus sequences was especially difficult in samples with low viral abundance. For example, three transcribed EVEs showed full-length segments, devoid of frameshift and nonsense mutations, exhibiting sufficient mean read depths that qualify them as exogenous virus hits. Mapping reads on a host genome containing EVEs before assembly somewhat alleviated the EVE burden, but it led to a drastic reduction of viral hits and reduced quality of assemblies, especially in regions of the viral genome relatively similar to EVEs. Our study highlights that our knowledge of the genetic diversity of viruses can be altered by the underestimated presence of EVEs in transcriptomic datasets, leading to false positives and altered or missing sequence information. Thus, recognizing and addressing the influence of EVEs in virus discovery pipelines will be key to enhancing our ability to capture the full spectrum of viral diversity.

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“…The misclassification of EVE sequences as exogenous viruses is a particularly underestimated possibility in virus discovery studies based on (meta)-transcriptomics datasets. Indeed, depending on their integration sites, EVEs can exploit nearby regulatory elements and the host cell’s transcriptional machinery, facilitating EVE transcription (Sofuku et al, 2018). While most described EVEs are highly mutated or fragmented, transcribing as non-coding RNAs, several have been discovered to encode intact open reading frames (ORFs) (Horie et al, 2010; Katzourakis & Gifford, 2010).…”

Section: Introductionmentioning

confidence: 99%

A tale of caution: How endogenous viral elements affect virus discovery in transcriptomic data

Brait,

Hackl,

Morel

et al. 2023

Preprint

0

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Large-scale metagenomic and -transcriptomic studies have revolutionized our understanding of viral diversity and abundance. In contrast, endogenous viral elements (EVEs), remnants of viral sequences integrated into host genomes, have received limited attention in the context of virus discovery, especially in RNA-Seq data. EVEs resemble their original viruses, a challenge that makes distinguishing between active infections and integrated remnants difficult, affecting virus classification and biases downstream analyses. Here, we systematically assess the effects of EVEs on a prototypical virus discovery pipeline, evaluate their impact on data integrity and classification accuracy, and provide some recommendations for better practices. We examined EVEs and exogenous viral sequences linked to Orthomyxoviridae, a diverse family of negative-sense segmented RNA viruses, in 13 genomic and 538 transcriptomic datasets of Culicinae mosquitoes. Our analysis revealed a substantial number of viral sequences in transcriptomic datasets. However, a significant portion appeared not to be exogenous viruses but transcripts derived from EVEs. Distinguishing between transcribed EVEs or exogenous virus sequences was especially difficult in samples with low viral abundance. For example, three transcribed EVEs showed full-length segments, devoid of frameshift and nonsense mutations, exhibiting sufficient mean read depths that qualify them as exogenous virus hits. Mapping reads on a host genome containing EVEs before assembly somewhat alleviated the EVE burden, but it led to a drastic reduction of viral hits and reduced quality of assemblies, especially in regions of the viral genome relatively similar to EVEs. Our study highlights that our knowledge of the genetic diversity of viruses can be altered by the underestimated presence of EVEs in transcriptomic datasets, leading to false positives and altered or missing sequence information. Thus, recognizing and addressing the influence of EVEs in virus discovery pipelines will be key to enhancing our ability to capture the full spectrum of viral diversity.

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Influence of Endogenous Viral Sequences on Gene Expression

Cited by 6 publications

References 65 publications

Roles of Human Endogenous Retroviruses and Endogenous Virus-Like Elements in Cancer Development and Innate Immunity

Roles of Human Endogenous Retroviruses and Endogenous Virus-Like Elements in Cancer Development and Innate Immunity

A tale of caution: How endogenous viral elements affect virus discovery in transcriptomic data

A tale of caution: How endogenous viral elements affect virus discovery in transcriptomic data

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