Retroviral integration: Site matters

Demeulemeester, Jonas; Rijck, Jan De; Gijsbers, Rik; Debyser, Zeger

doi:10.1002/bies.201500051

Cited by 63 publications

(33 citation statements)

References 126 publications

(229 reference statements)

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“…The integrase protein interacts with tethering proteins that guide the preintegration viral complex into specific chromatin contexts. The final integration site, usually in bendable DNA sites on nucleosomal DNA, shows weak nucleotide sequence preference (58,59). Our finding that CcBV circle integration is not totally random but does not appear to involve a precise integration site thus is similar to results observed for retroviruses.…”

Section: Discussionsupporting

confidence: 83%

Cotesia congregata Bracovirus Circles Encoding PTP and Ankyrin Genes Integrate into the DNA of Parasitized Manduca sexta Hemocytes

Chevignon

Périquet

Gyapay

et al. 2018

J Virol

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Polydnaviruses (PDVs) are essential for the parasitism success of tens of thousands of species of parasitoid wasps. PDVs are present in wasp genomes as proviruses, which serve as the template for the production of double-stranded circular viral DNA carrying virulence genes that are injected into lepidopteran hosts. PDV circles do not contain genes coding for particle production, thereby impeding viral replication in caterpillar hosts during parasitism. Here, we investigated the fate of PDV circles of Cotesia congregata bracovirus during parasitism of the tobacco hornworm, , by the wasp Sequences sharing similarities with host integration motifs (HIMs) of Microplitis demolitor bracovirus (MdBV) circles involved in integration into DNA could be identified in 12 CcBV circles, which encode and gene families involved in host immune disruption. A PCR approach performed on a subset of these circles indicated that they persisted in parasitized hemocytes as linear forms, possibly integrated in host DNA. Furthermore, by using a primer extension capture method based on these HIMs and high-throughput sequencing, we could show that 8 out of 9 circles tested were integrated in hemocyte genomic DNA and that integration had occurred specifically using the HIM, indicating that an HIM-mediated specific mechanism was involved in their integration. Investigation of BV circle insertion sites at the genome scale revealed that certain genomic regions appeared to be enriched in BV insertions, but no specific target site could be identified. The identification of a specific and efficient integration mechanism shared by several bracovirus species opens the question of its role in braconid parasitoid wasp parasitism success. Indeed, results obtained here show massive integration of bracovirus DNA in somatic immune cells at each parasitism event of a caterpillar host. Given that bracoviruses do not replicate in infected cells, integration of viral sequences in host DNA might allow the production of PTP and VANK virulence proteins within newly dividing cells of caterpillar hosts that continue to develop during parasitism. Furthermore, this integration process could serve as a basis to understand how PDVs mediate the recently identified gene flux between parasitoid wasps and Lepidoptera and the frequency of these horizontal transfer events in nature.

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Section: Discussionsupporting

confidence: 83%

Cotesia congregata Bracovirus Circles Encoding PTP and Ankyrin Genes Integrate into the DNA of Parasitized Manduca sexta Hemocytes

Chevignon

Périquet

Gyapay

et al. 2018

J Virol

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“…Those who would like additional background information can consult recent reviews (Demeulemeester et al, 2015; Serrao and Engelman, 2016). …”

Section: Introductionmentioning

confidence: 99%

What Integration Sites Tell Us about HIV Persistence

Hughes

Coffin

2016

Cell Host & Microbe

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Summary Advances in technology have made it possible to analyze integration sites in cells from HIV infected patients. A significant fraction of infected cells in patients on long-term therapy are clonally expanded; in some cases the integrated viral DNA contributes to the clonal expansion of the infected cells. Although the large majority (>95%) of the HIV proviruses in treated patients are defective, expanded clones can carry replication competent proviruses, and cells from these clones can release infectious virus. As discussed in this Perspective, it is likely that cells that produce virus are strongly selected against in vivo, and cells with replication competent proviruses expand and survive because only a small fraction of the cells produce virus. These findings have implications for strategies that are intended to eliminate the reservoir of infected cells that has made it almost impossible to cure HIV infected patients.

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“…Nevertheless, the introduction of effective machine learning techniques, e.g., using transfer learning to transfer the cell line knowledge to patient samples would also be an interesting future direction to explore. As integration-associated virus latency is attracting more and more research interest [59], we believe that our DeepHINT framework together with more emerging experimental data [15] and improved experimental techniques [60] will offer more useful insights into the studies of HIV integration in the genome. Figure 1: Schematic overview of the DeepHINT pipeline.…”

Section: Discussionmentioning

confidence: 99%

DeepHINT: Understanding HIV-1 integration via deep learning with attention

Xiao

Zhang

et al. 2018

Preprint

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Motivation: Human immunodeficiency virus type 1 (HIV-1) genome integration is closely related to clinical latency and viral rebound. In addition to human DNA sequences that directly interact with the integration machinery, the selection of HIV integration sites has also been shown to depend on the heterogeneous genomic context around a large region, which greatly hinders the prediction and mechanistic studies of HIV integration.Results: We have developed an attention-based deep learning framework, named DeepHINT, to simultaneously provide accurate prediction of HIV integration sites and mechanistic explanations of the detected sites. Extensive tests on a high-density HIV integration site dataset showed that DeepHINT can outperform conventional modeling strategies by automatically learning the genomic context of HIV integration solely from primary DNA sequence information. Systematic analyses on diverse known factors of HIV integration further validated the biological relevance of the prediction result. More importantly, in-depth analyses of the attention values output by DeepHINT revealed intriguing mechanistic implications in the selection of HIV integration sites, including potential roles of several basic helix-loop-helix (bHLH) transcription factors and zincfinger proteins. These results established DeepHINT as an effective and explainable deep learning framework for the prediction and mechanistic study of HIV integration. Availability: DeepHINT is available as an open-source software and can be downloaded from https://github.com/nonnerdling/DeepHINT Contact:

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Retroviral integration: Site matters

Cited by 63 publications

References 126 publications

Cotesia congregata Bracovirus Circles Encoding PTP and Ankyrin Genes Integrate into the DNA of Parasitized Manduca sexta Hemocytes

Cotesia congregata Bracovirus Circles Encoding PTP and Ankyrin Genes Integrate into the DNA of Parasitized Manduca sexta Hemocytes

What Integration Sites Tell Us about HIV Persistence

DeepHINT: Understanding HIV-1 integration via deep learning with attention

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