Virus dynamics and phyloanatomy: Merging population dynamic and phylogenetic approaches

Bons, Eva; Regoes, Roland R.

doi:10.1111/imr.12688

Cited by 12 publications

(14 citation statements)

References 131 publications

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“…This observation highlights the need to carefully assess the validity of phylogenetic methods that rely on the assumption of neutral evolution when analyzing within-host evolution of HIV-1, in particular phyloanatomic analyses (Salemi and Rife 2016; Lorenzo-Redondo et al. 2016; Bons and Regoes 2018). We also provide insights into how viral population sequencing data can be used to alleviate problems of phylogenetic reconstruction and analyze sequence diversity to predict evolutionary outcomes.…”

Section: Introductionmentioning

confidence: 99%

Parallel Evolution of HIV-1 in a Long-Term Experiment

Bertels

Leemann

Metzner

et al. 2019

Molecular Biology and Evolution

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One of the most intriguing puzzles in biology is the degree to which evolution is repeatable. The repeatability of evolution, or parallel evolution, has been studied in a variety of model systems, but has rarely been investigated with clinically relevant viruses. To investigate parallel evolution of HIV-1, we passaged two replicate HIV-1 populations for almost 1 year in each of two human T-cell lines. For each of the four evolution lines, we determined the genetic composition of the viral population at nine time points by deep sequencing the entire genome. Mutations that were carried by the majority of the viral population accumulated continuously over 1 year in each evolution line. Many majority mutations appeared in more than one evolution line, that is, our experiments showed an extreme degree of parallel evolution. In one of the evolution lines, 62% of the majority mutations also occur in another line. The parallelism impairs our ability to reconstruct the evolutionary history by phylogenetic methods. We show that one can infer the correct phylogenetic topology by including minority mutations in our analysis. We also find that mutation diversity at the beginning of the experiment is predictive of the frequency of majority mutations at the end of the experiment.

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Section: Introductionmentioning

confidence: 99%

Parallel Evolution of HIV-1 in a Long-Term Experiment

Bertels

Leemann

Metzner

et al. 2019

Molecular Biology and Evolution

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“…We purposely chose this experimental design to control for the variation expected if experimentally or naturally infected animals were used, in order to establish a technical protocol for intrahost phylogenetic studies. This allowed us to determine, without bias, the best methods for obtaining consistent virus RNA for downstream sequencing experiments to contribute to the newly emerging field of phyloanatomy (34, 35). In both natural and experimental infection, several publications have demonstrated that WNV infection in the equine brain and spinal cord is multifocal (14–17).…”

Section: Discussionmentioning

confidence: 99%

“…We incorporated PCR into this protocol because prior literature indicates inconsistent results in sequencing output in the face of positive real time rtPCR results in equine WNV infection (35). This is especially important for WNV disease in horses where virus is highly variable regionally in the CNS.…”

Section: Discussionmentioning

confidence: 99%

Viral Enrichment Methods Affect the Detection but Not Sequence Variation of West Nile Virus in Equine Brain Tissue

et al. 2018

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West Nile virus (WNV), a small, positive sense, single stranded RNA virus continues to encroach into new locales with emergence of new viral variants. Neurological disease in the equine can be moderate to severe in the face of low to undetectable virus loads. Physical methods of virus enrichment may increase sensitivity of virus detection and enhance analysis of viral diversity, especially for deep sequencing studies. However, the use of these techniques is limited mainly to non-neural tissues. We investigated the hypothesis that elimination of equine brain RNA enhances viral detection without limiting viral variation. Eight different WNV viral RNA enrichment and host RNA separation methods were evaluated to determine if elimination of host RNA enhanced detection of WNV and increase the repertoire of virus variants for sequencing. Archived brain tissue from 21 different horses was inoculated with WNV, homogenized, before enrichment and separation. The protocols utilized combinations of low-speed centrifugation, syringe filtration, and nuclease treatment. Viral and host RNA were analyzed using real-time PCR targeting the WNV Envelope (E) protein and equine G3PDH to determine relative sensitivity for WNV and host depletion, respectively. To determine the effect of these methods on viral variation, deep sequencing of the E protein was performed. Our results demonstrate that additional separation and enrichment methods resulted in loss of virus in the face of host RNA depletion. DNA sequencing showed no significant difference in total sequence variation between the RNA enrichment protocols. For equine brain infected with WNV, direct RNA extraction followed by host RNA depletion was most suitable. This study highlights the importance of evaluating viral enrichment and separation methods according to tissue type before embarking on studies where quantification of virus and viral variants is essential to the outcome of the study.

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“…This tripartite interplay is referred to as G*G*E interactions in ecology and evolution, while epidemiologists often pinpoint individual edges in this interaction network and refer to them as cofactors. Third, the notion of 'environment' for a viral infection must be understood as a Russian-doll hierarchical integration across levels, from the virocell to the ecology: cell type diversity may display different permissivity to the infection and different potential for malignization (in the case of HPV, see [8]); tissue diversity may differentially foster malignancy [9]; organ diversity may introduce within-patient structuring of the viral population [10]; individual behaviour may strongly impact viral circulation; biological and physico-chemical agents may modify the host-pathogen interaction; and human population structure will undoubtedly pattern viral population structure. In summary, to understand DNA oncovirus virulence, it is necessary to adopt a multi-scale approach and bridge the cellular and the population levels.…”

Section: Dna Oncoviruses: Low Infection Virulence and High Disease Bumentioning

confidence: 99%

Towards a multi-level and a multi-disciplinary approach to DNA oncovirus virulence

Alizon

Bravo

Farrell

et al. 2019

Phil. Trans. R. Soc. B

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One out of 10 cancers is estimated to arise from infections by a handful of oncogenic viruses. These infectious cancers constitute an opportunity for primary prevention through immunization against the viral infection, for early screening through molecular detection of the infectious agent, and potentially for specific treatments, by targeting the virus as a marker of cancer cells. Accomplishing these objectives will require a detailed understanding of the natural history of infections, the mechanisms by which the viruses contribute to disease, the mutual adaptation of viruses and hosts, and the possible viral evolution in the absence and in the presence of the public health interventions conceived to target them. This issue showcases the current developments in experimental tissue-like and animal systems, mathematical models and evolutionary approaches to understand DNA oncoviruses. Our global aim is to provide proximate explanations to the present-day interface and interactions between virus and host, as well as ultimate explanations about the adaptive value of these interactions and about the evolutionary pathways that have led to the current malignant phenotype of oncoviral infections. This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.

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Virus dynamics and phyloanatomy: Merging population dynamic and phylogenetic approaches

Cited by 12 publications

References 131 publications

Parallel Evolution of HIV-1 in a Long-Term Experiment

Parallel Evolution of HIV-1 in a Long-Term Experiment

Viral Enrichment Methods Affect the Detection but Not Sequence Variation of West Nile Virus in Equine Brain Tissue

Towards a multi-level and a multi-disciplinary approach to DNA oncovirus virulence

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