The Contribution of Viral Genotype to Plasma Viral Set-Point in HIV Infection

Hodcroft, Emma B.; Hadfield, Jarrod D.; Fearnhill, Esther; Phillips, Andrew; Dunn, David; O’Shea, Siobhan; Pillay, Deenan; Brown, Andrew J. Leigh

doi:10.1371/journal.ppat.1004112

Cited by 47 publications

(80 citation statements)

References 87 publications

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“…For each gene tree, ML was estimated using IQTree (with automatic evolutionary model selection, as mentioned above), each with 1,000 ultrafast bootstraps. Branches with less than 70% support were collapsed using TreeCollapseCL4 (HODCROFT et al, 2014), in order to decrease the likelihood of false positives (i.e. clades that did not really exist).…”

Section: Phylogenymentioning

confidence: 99%

“…incomplete lineage sorting, gene duplication and/or gene loss).The MulRF method produces more accurate species trees than other gene tree parsimony approaches (CHAUDHARY et al, 2013). Nevertheless, because it works like a consensus tree, no nodal supports are available, so this issue must be overcome beforehand; we did this by collapsing branches with less than 70% support in each gene tree using TreeCollapseCL4 (HODCROFT et al, 2014), as mentioned above.…”

Section: Phylogenymentioning

confidence: 99%

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Gut transcriptome analysis on females of Ornithodoros mimon (Acari: Argasidae) and phylogenetic inference of ticks

Landulfo

Patané

Silva

et al. 2017

Rev. Bras. Parasitol. Vet.

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Ornithodoros mimon is an argasid tick that parasitizes bats, birds and opossums and is also harmful to humans. Knowledge of the transcripts present in the tick gut helps in understanding the role of vital molecules in the digestion process and parasite-host relationship, while also providing information about the evolution of arthropod hematophagy. Thus, the present study aimed to know and ascertain the main molecules expressed in the gut of argasid after their blood meal, through analysis on the gut transcriptome of engorged females of O. mimon using 454-based RNA sequencing. The gut transcriptome analysis reveals several transcripts associated with hemoglobin digestion, such as serine, cysteine, aspartic proteases and metalloenzymes. The phylogenetic analysis on the peptidases confirmed that most of them are clustered with other tick genes. We recorded the presence a cathepsin O peptidase-coding transcript in ticks. The topology of the phylogenetic inferences, based on transcripts of inferred families of homologues, was similar to that of previous reports based on mitochondrial genome and nuclear rRNA sequences. We deposited 2,213 sequence of O. mimon to the public databases. Our findings may help towards better understanding of important argasid metabolic processes, such as digestion, nutrition and immunity.Keywords: Argasidae, transcriptome, gut, phylogeny, Ornithodoros mimon. ResumoOrnithodoros mimon é um carrapato argasídeo parasita de morcegos, aves e marsupiais, além de ser bastante agressivo aos humanos. O conhecimento dos transcritos presentes no intestino dos carrapatos auxilia no entendimento do papel de moléculas vitais no processo de digestão e na relação parasito-hospedeiro, além de fornecer também informações sobre a evolução dos artrópodes hematófagos. Desta maneira, o presente estudo teve como objetivo conhecer e identificar as principais moléculas expressas no intestino de uma espécie de carrapato argasídeo após o repasto sanguíneo, através de uma análise transcritômica descritiva do intestino de fêmeas ingurgitadas de O. mimon, utilizando um sequenciamento de RNA de nova geração da plataforma 454. Além de inferir a relação filogenética de carrapatos através de um conjunto de dados transcritômicos. O transcriptoma do intestino revelou diversos transcritos associados com a digestão da hemoglobina, como proteinases das classes serino, cisteína, aspártica e metalo. Registramos a presença de um transcrito de uma cisteína peptidase do tipo catepsina O em carrapatos. A inferência filogenética baseada em conjunto de dados transcritos homólogos tem uma resolução topológica similar a de outros conjuntos de dados moleculares. Foram depositados no banco de dados gênico público 2213 transcritos de O. mimon. Os achados obtidos no presente estudo podem contribuir para compreensão dos importantes processos, como digestão, nutrição e imunidade dos carrapatos da família Argasidae, além de fornecer informações sobre a filogenia da ordem Ixodida.

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Section: Phylogenymentioning

confidence: 99%

Section: Phylogenymentioning

confidence: 99%

Gut transcriptome analysis on females of Ornithodoros mimon (Acari: Argasidae) and phylogenetic inference of ticks

Landulfo

Patané

Silva

et al. 2017

Rev. Bras. Parasitol. Vet.

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“…Various phylogenetic methods have previously been employed to estimate the heritability of SPVL [7,9,21]. All of these methods have been developed in the context of ecological species and have yet to be validated for use on viral populations.…”

Section: Phylogenetic Methodsmentioning

confidence: 99%

“…In order to illustrate the effects of incorrect model assumptions about the evolutionary process underlying the phylogenetic methods, we compare the different estimation methods using mock data from simulations ( used to validate the respective heritability estimates for SPVL in HIV [7,9,26], the simulation models differ between publications and generally do not adequately represent key aspects of the evolution of SPVL across infections. Here, we use a simple previously published model for HIV transmission across many generations in a Wright-Fisher population that accounts for transmission bottlenecks and intra-host evolution [20].…”

Section: Heritability Estimation In Simulated Populationsmentioning

confidence: 99%

Potential pitfalls in estimating viral load heritability

Leventhal

Bonhoeffer

2016

Preprint

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In HIV patients, the set-point viral load (SPVL) is the most widely used predictor of disease severity. Yet SPVL varies over several orders of magnitude between patients. The heritability of SPVL quantifies how much of the variation in SPVL is due to transmissible viral genetics. There is currently no clear consensus on the value of SPVL heritability, as multiple studies have reported apparently discrepant estimates. Here we illustrate that the discrepancies in estimates are most likely due to differences in the estimation methods, rather than the study populations. Importantly, phylogenetic estimates run the risk of being strongly confounded by unrealistic model assumptions. Care must be taken when interpreting and comparing the different estimates to each other. . CC-BY-NC-ND 4.0 International license peer-reviewed) is the author/funder. It is made available under aThe copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/046797 doi: bioRxiv preprint first posted online Apr. 3, 2016; Searching for set-point viral load heritability in HIV infectionDuring the asymptomatic phase of HIV infection, the viral load within a patient fluctuates around a relatively stable value known as the set-point viral load. Set-point viral load (SPVL) has proven to be highly relevant, as untreated patients with higher SPVL tend to progress to AIDS faster than those with low SPVL, and consequentially SPVL is one of the most widely used predictors of disease severity [1,2]. What is particularly striking, however, is the amount of variation in SPVL between patients: SPVL varies over several orders of magnitude between patients [1, [3][4][5]. Understanding the source of this wide variation in SPVL in the patient population is key to understanding HIV pathogenicity and why certain patients progress to AIDS rather quickly, while others progress much more slowly or not at all.The potential contributions to SPVL variation can generally be split into four categories, determined by:(i) the specific genetic viral variant that infects a host; (ii) the host genetics; (iii) any interactions between host and viral genetics; (iv) other extrinsic factors, both independent of and interacting with host and viral genetics. From a virus-centric view, we can group contributions (ii)-(iv) together, and hence the question becomes to what degree the variation in HIV genetics explains the variation in SPVL in the patient population, and by proxy how much viral genetics control the variation HIV pathogenicity.New HIV infections can occur after a virus is transmitted from a donor host to a recipient host. Thus, from an evolutionary point of view, viral genetic information is passed on and conserved from one infection to the next, whereas donor and recipient host genetics are typically unrelated. In evolutionary theory, the concept of heritability quantifies precisely the question at hand [6]: How much of the observed variation in a trait is explained by variation in the genetics that are passed on to the next generation? A ...

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“…Individuals infected with subtype C or D HIV-1 have more rapid disease progression than those infected with subtype A (12-14). There is a trend for transmission pairs to have more similar SPVL than if there was no transmission link (15,16). The viral capsid protein, present within the Gag polyprotein precursor, is the site of important T-cell epitope targets, and immune responses to Gag can be more important than responses to other viral proteins in terms of controlling viral replication (17,18).…”

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confidence: 99%