scholarly journals PHYLOSCANNER: Inferring Transmission from Within‐ and Between-Host Pathogen Genetic Diversity

2017 ◽  
Author(s):  
Chris Wymant ◽  
Matthew Hall ◽  
Oliver Ratmann ◽  
David Bonsall ◽  
Tanya Golubchik ◽  
...  
Keyword(s):  
Sequence Data ◽  
Infected Individual ◽  
Software Tool ◽  
Central Feature ◽  
Bacterial Cells ◽  
Pathogen Diversity ◽  
Oxford Nanopore ◽  
Host Evolution ◽  
Hiv 1 ◽  
Roche 454

AbstractA central feature of pathogen genomics is that different infectious particles (virions, bacterial cells, etc.) within an infected individual may be genetically distinct, with patterns of relatedness amongst infectious particles being the result of both within-host evolution and transmission from one host to the next. Here we present a new software tool, phyloscanner, which analyses pathogen diversity from multiple infected hosts. phyloscanner provides unprecedented resolution into the transmission process, allowing inference of the direction of transmission from sequence data alone. Multiply infected individuals are also identified, as they harbour subpopulations of infectious particles that are not connected by within-host evolution, except where recombinant types emerge. Low-level contamination is flagged and removed. We illustrate phyloscanner on both viral and bacterial pathogens, namely HIV-1 sequenced on Illumina and Roche 454 platforms, HCV sequenced with the Oxford Nanopore MinION platform, and Streptococcus pneumoniae with sequences from multiple colonies per individual. phyloscanner is available from https://github.com/BDI-pathogens/phyloscanner.

scholarly journals Identifying likely transmission pairs with pathogen sequence data using Kolmogorov Forward Equations; an application to M.bovis in cattle and badgers

2020 ◽  
Author(s):  
Gianluigi Rossi ◽  
Joseph Crispell ◽  
Daniel Balaz ◽  
Samantha J. Lycett ◽  
Richard J. Delahay ◽  
...  
Keyword(s):  
Sequence Data ◽  
Epidemiological Data ◽  
Transmission Probability ◽  
Clock Signal ◽  
Nucleotide Polymorphisms ◽  
Pathogen Diversity ◽  
Infection Pathways ◽  
Computationally Intensive ◽  
Forward Equations ◽  
Host Evolution

AbstractEstablished methods for whole-genome-sequencing (WGS) technology allow for the detection of single-nucleotide polymorphisms (SNPs) in the pathogen genomes sourced from host samples. The information obtained can be used to track the pathogen’s evolution in time and potentially identify ‘who-infected-whom’ with unprecedented accuracy. Successful methods include ‘phylodynamic approaches’ that integrate evolutionary and epidemiological data. However, they are typically computationally intensive, require extensive data, and are best applied when there is a strong molecular clock signal and substantial pathogen diversity.To determine how much transmission information can be inferred when pathogen genetic diversity is low and metadata limited, we propose an analytical approach that combines pathogen WGS data and sampling times from infected hosts. It accounts for ‘between-scale’ processes, in particular within-host pathogen evolution and between-host transmission. We applied this to a well-characterised population with an endemic Mycobacterium bovis (the causative agent of bovine/zoonotic tuberculosis, bTB) infection.Our results show that, even with such limited data and low diversity, the computation of the transmission probability between host pairs can help discriminate between likely and unlikely infection pathways and therefore help to identify potential transmission networks, but can be sensitive to assumptions about within-host evolution.

scholarly journals Prevalence of Non-B HIV-1 Subtypes in North Italy and Analysis of Transmission Clusters Based on Sequence Data Analysis

2019 ◽  
Vol 8 (1) ◽  
pp. 36 ◽  
Author(s):  
Giovanni Lorenzin ◽  
Franco Gargiulo ◽  
Arnaldo Caruso ◽  
Francesca Caccuri ◽  
Emanuele Focà ◽  
...  
Keyword(s):  
Public Health ◽  
Sequence Data ◽  
Human Mobility ◽  
Heterosexual Couples ◽  
Molecular Surveillance ◽  
Coalescence Model ◽  
Coding Regions ◽  
Hiv Epidemic ◽  
Viral Subtypes ◽  
Hiv 1

HIV-1 diversity is increasing in European countries due to immigration flows, as well as travels and human mobility, leading to the circulation of both new viral subtypes and new recombinant forms, with important implications for public health. We analyzed 710 HIV-1 sequences comprising protease and reverse-transcriptase (PR/RT) coding regions, sampled from 2011 to 2017, from naive patients in Spedali Civili Hospital, Brescia, Italy. Subtyping was performed by using a combination of different tools; the phylogenetic analysis with a structured coalescence model and Makarov Chain Monte Carlo was used on the datasets, to determine clusters and evolution. We detected 304 (43%) patients infected with HIV-1 non-B variants, of which only 293 sequences were available, with four pure subtypes and five recombinant forms; subtype F1 (17%) and CRF02_AG (51.1%) were most common. Twenty-five transmission clusters were identified, three of which included >10 patients, belonging to subtype CRF02_AG and subtype F. Most cases of alleged transmission were between heterosexual couples. Probably due to strong migratory flows, we have identified different subtypes with particular patterns of recombination or, as in the case of the subtype G (18/293, 6.1%), to a complete lack of relationship between the sequenced strains, revealing that they are all singletons. Continued HIV molecular surveillance is most important to analyze the dynamics of the boost of transmission clusters in order to implement public health interventions aimed at controlling the HIV epidemic.

scholarly journals Ontogeny and Specificities of Mucosal and Blood Human Immunodeficiency Virus Type 1-Specific CD8+ Cytotoxic T Lymphocytes

2003 ◽  
Vol 77 (1) ◽  
pp. 291-300 ◽  
Author(s):  
L. Musey ◽  
Y. Ding ◽  
J. Cao ◽  
J. Lee ◽  
C. Galloway ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Cytotoxic T Lymphocyte ◽  
Infected Individual ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Induction of adaptive immunity to human immunodeficiency virus type 1 (HIV-1) at the mucosal site of transmission is poorly understood but crucial in devising strategies to control and prevent infection. To gain further understanding of HIV-1-specific T-cell mucosal immunity, we established HIV-1-specific CD8+ cytotoxic T-lymphocyte (CTL) cell lines and clones from the blood, cervix, rectum, and semen of 12 HIV-1-infected individuals and compared their specificities, cytolytic function, and T-cell receptor (TCR) clonotypes. Blood and mucosal CD8+ CTL had common HIV-1 epitope specificities and major histocompatibility complex restriction patterns. Moreover, both systemic and mucosal CTL lysed targets with similar efficiency, primarily through the perforin-dependent pathway in in vitro studies. Sequence analysis of the TCRβ VDJ region revealed in some cases identical HIV-1-specific CTL clones in different compartments in the same HIV-1-infected individual. These results clearly establish that a subset of blood and mucosal HIV-1-specific CTL can have a common origin and can traffic between anatomically distinct compartments. Thus, these effectors can provide immune surveillance at the mucosa, where rapid responses are needed to contain HIV-1 infection.

scholarly journals Detection of novel HIV-1 drug resistance mutations by support vector analysis of deep sequence data and experimental validation

2019 ◽  
Author(s):  
Mariano Avino ◽  
Emmanuel Ndashimye ◽  
Daniel J. Lizotte ◽  
Abayomi S. Olabode ◽  
Richard M. Gibson ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Drug Treatment ◽  
Treatment Outcomes ◽  
Sequence Data ◽  
Wild Type Virus ◽  
Support Vector ◽  
Wild Type ◽  
Subtype B ◽  
The World ◽  
Hiv 1

AbstractThe global HIV-1 pandemic comprises many genetically divergent subtypes. Most of our understanding of drug resistance in HIV-1 derives from subtype B, which predominates in North America and western Europe. However, about 90% of the pandemic represents non-subtype B infections. Here, we use deep sequencing to analyze HIV-1 from infected individuals in Uganda who were either treatment-naïve or who experienced virologic failure on ART without the expected patterns of drug resistance. Our objective was to detect potentially novel associations between mutations in HIV-1 integrase and treatment outcomes in Uganda, where most infections are subtypes A or D. We retrieved a total of 380 archived plasma samples from patients at the Joint Clinical Research Centre (Kampala), of which 328 were integrase inhibitor-naïve and 52 were raltegravir (RAL)-based treatment failures. Next, we developed a bioinformatic pipeline for alignment and variant calling of the deep sequence data obtained from these samples from a MiSeq platform (Illumina). To detect associations between within-patient polymorphisms and treatment outcomes, we used a support vector machine (SVM) for feature selection with multiple imputation to account for partial reads and low quality base calls. Candidate point mutations of interest were experimentally introduced into the HIV-1 subtype B NL4-3 backbone to determine susceptibility to RAL in U87.CD4.CXCR4 cells. Finally, we carried out replication capacity experiments with wild-type and mutant viruses in TZM-bl cells in the presence and absence of RAL. Our analyses not only identified the known major mutation N155H and accessory mutations G163R and V151I, but also novel mutations I203M and I208L as most highly associated with RAL failure. The I203M and I208L mutations resulted in significantly decreased susceptibility to RAL (44.0-fold and 54.9-fold, respectively) compared to wild-type virus (EC50=0.32 nM), and may represent novel pathways of HIV-1 resistance to modern treatments.Author summaryThere are many different types of HIV-1 around the world. Most of the research on how HIV-1 can become resistant to drug treatment has focused on the type (B) that is the most common in high-income countries. However, about 90% of infections around the world are caused by a type other than B. We used next-generation sequencing to analyze samples of HIV-1 from patients in Uganda (mostly infected by types A and D) for whom drug treatment failed to work, and whose infections did not fit the classic pattern of adaptation based on B. Next, we used machine learning to detect mutations in these virus populations that could explain the treatment outcomes. Finally, we experimentally added two candidate mutations identified by our analysis to a laboratory strain of HIV-1 and confirmed that they conferred drug resistance to the virus. Our study reveals new pathways that other types of HIV-1 may use to evolve resistance to drugs that make up the current recommended treatment for newly diagnosed individuals.

scholarly journals NanoHIV: A Bioinformatics Pipeline for Producing Accurate, Near Full-Length HIV Proviral Genomes Sequenced Using the Oxford Nanopore Technology

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2577
Author(s):  
Imogen A. Wright ◽  
Kayla E. Delaney ◽  
Mary Grace K. Katusiime ◽  
Johannes C. Botha ◽  
Susan Engelbrecht ◽  
...  
Keyword(s):  
Pcr Amplification ◽  
Cost Effective ◽  
Full Length ◽  
Sequencing Error ◽  
Consensus Building ◽  
Genome Sequences ◽  
Bioinformatics Pipeline ◽  
Oxford Nanopore ◽  
Single Genome ◽  
Hiv 1

HIV-1 proviral single-genome sequencing by limiting-dilution polymerase chain reaction (PCR) amplification is important for differentiating the sequence-intact from defective proviruses that persist during antiretroviral therapy (ART). Intact proviruses may rebound if ART is interrupted and are the barrier to an HIV cure. Oxford Nanopore Technologies (ONT) sequencing offers a promising, cost-effective approach to the sequencing of long amplicons such as near full-length HIV-1 proviruses, but the high diversity of HIV-1 and the ONT sequencing error render analysis of the generated data difficult. NanoHIV is a new tool that uses an iterative consensus generation approach to construct accurate, near full-length HIV-1 proviral single-genome sequences from ONT data. To validate the approach, single-genome sequences generated using NanoHIV consensus building were compared to Illumina® consensus building of the same nine single-genome near full-length amplicons and an average agreement of 99.4% was found between the two sequencing approaches.

scholarly journals Retrospective screening of routine respiratory samples revealed undetected community transmission and missed intervention opportunities for SARS-CoV-2 in the United Kingdom

2021 ◽  
Vol 102 (6) ◽  
Author(s):  
Joseph G. Chappell ◽  
Theocharis Tsoleridis ◽  
Gemma Clark ◽  
Louise Berry ◽  
Nadine Holmes ◽  
...  
Keyword(s):  
Sequence Data ◽  
Infected Individual ◽  
Case Definition ◽  
Case Definitions ◽  
Risk Area ◽  
High Risk Area ◽  
Epidemiological Risk ◽  
Distinct Lineage ◽  
The Uk ◽  
Archival Specimens

In the early phases of the SARS coronavirus type 2 (SARS-CoV-2) pandemic, testing focused on individuals fitting a strict case definition involving a limited set of symptoms together with an identified epidemiological risk, such as contact with an infected individual or travel to a high-risk area. To assess whether this impaired our ability to detect and control early introductions of the virus into the UK, we PCR-tested archival specimens collected on admission to a large UK teaching hospital who retrospectively were identified as having a clinical presentation compatible with COVID-19. In addition, we screened available archival specimens submitted for respiratory virus diagnosis, and dating back to early January 2020, for the presence of SARS-CoV-2 RNA. Our data provides evidence for widespread community circulation of SARS-CoV-2 in early February 2020 and into March that was undetected at the time due to restrictive case definitions informing testing policy. Genome sequence data showed that many of these early cases were infected with a distinct lineage of the virus. Sequences obtained from the first officially recorded case in Nottinghamshire - a traveller returning from Daegu, South Korea – also clustered with these early UK sequences suggesting acquisition of the virus occurred in the UK and not Daegu. Analysis of a larger sample of sequences obtained in the Nottinghamshire area revealed multiple viral introductions, mainly in late February and through March. These data highlight the importance of timely and extensive community testing to prevent future widespread transmission of the virus.

scholarly journals Case report of three consecutive lues maligna infections in an HIV-infected patient

2016 ◽  
Vol 28 (5) ◽  
pp. 523-525 ◽  
Author(s):  
Stefanie Sammet ◽  
Rika Draenert
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Infected Patient ◽  
Infected Individual ◽  
Treponema Pallidum ◽  
First Episode ◽  
Rare Presentation ◽  
Cd4 Cell Count ◽  
Highly Active ◽  
Cd4 Cell ◽  
Hiv 1

Lues maligna is a rare presentation of an infection with Treponema pallidum. Here we report three lues maligna infections with severe dermatological manifestations in a single HIV-1 infected individual. Despite the start of highly active antiretroviral therapy and a substantial increase in CD4 cell count after the first episode, he developed consecutive episodes. We assume a specific immunological predisposition to react to T. pallidum in this patient.

VisFeature: a stand-alone program for visualizing and analyzing statistical features of biological sequences

2019 ◽  
Author(s):  
Jun Wang ◽  
Pu-Feng Du ◽  
Xin-Yu Xue ◽  
Guang-Ping Li ◽  
Yuan-Ke Zhou ◽  
...  
Keyword(s):  
Sequence Data ◽  
Software Tool ◽  
Data Retrieval ◽  
Supplementary Information ◽  
Statistical Features ◽  
Biological Sequence ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Source Codes ◽  
Multiple Sequence Alignments

Abstract Summary Many efforts have been made in developing bioinformatics algorithms to predict functional attributes of genes and proteins from their primary sequences. One challenge in this process is to intuitively analyze and to understand the statistical features that have been selected by heuristic or iterative methods. In this paper, we developed VisFeature, which aims to be a helpful software tool that allows the users to intuitively visualize and analyze statistical features of all types of biological sequence, including DNA, RNA and proteins. VisFeature also integrates sequence data retrieval, multiple sequence alignments and statistical feature generation functions. Availability and implementation VisFeature is a desktop application that is implemented using JavaScript/Electron and R. The source codes of VisFeature are freely accessible from the GitHub repository (https://github.com/wangjun1996/VisFeature). The binary release, which includes an example dataset, can be freely downloaded from the same GitHub repository (https://github.com/wangjun1996/VisFeature/releases). Contact [email protected] or [email protected] Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Expression of MDM2 in Macrophages Promotes the Early Postentry Steps of HIV-1 Infection through Inhibition of p53

2019 ◽  
Vol 93 (7) ◽  
Author(s):  
Yann Breton ◽  
Vincent Desrosiers ◽  
Michel Ouellet ◽  
Alexandre Deshiere ◽  
Cynthia Torresilla ◽  
...  
Keyword(s):  
Infected Individual ◽  
Human Monocyte ◽  
Careful Analysis ◽  
Binding Activity ◽  
Individual Identification ◽  
Small Interfering Rnas ◽  
Viral Reservoirs ◽  
Cellular Environment ◽  
Hiv 1

ABSTRACT The molecular basis for HIV-1 susceptibility in primary human monocyte-derived macrophages (MDMs) was previously evaluated by comparing the transcriptome of infected and bystander populations. Careful analysis of the data suggested that the ubiquitin ligase MDM2 acted as a positive regulator of HIV-1 replication in MDMs. In this study, MDM2 silencing through transcript-specific small interfering RNAs in MDMs induced a reduction in HIV-1 reverse transcription and integration along with an increase in the expression of p53-induced genes, including CDKN1A. Experiments with Nutlin-3, a pharmacological inhibitor of MDM2 p53-binding activity, showed a similar effect on HIV-1 infection, suggesting that the observed restriction in HIV-1 production results from the release/activation of p53 and not the absence of MDM2 per se. Knockdown and inhibition of MDM2 also both correlate with a decrease in the Thr592-phosphorylated inactive form of SAMHD1. The expression level of MDM2 and the p53 activation status are therefore important factors in the overall susceptibility of macrophages to HIV-1 infection, bringing a new understanding of signaling events controlling the process of virus replication in this cell type. IMPORTANCE Macrophages, with their long life span in vivo and their resistance to HIV-1-mediated cytopathic effect, might serve as viral reservoirs, contributing to virus persistence in an infected individual. Identification of host factors that increase the overall susceptibility of macrophages to HIV-1 might provide new therapeutic targets for the efficient control of viral replication in these cells and limit the formation of reservoirs in exposed individuals. In this study, we demonstrate the importance of p53 regulation by MDM2, which creates a cellular environment more favorable to the early steps of HIV-1 replication. Moreover, we show that p53 stabilization reduces virus infection in human macrophages, highlighting the important role of p53 in antiviral immunity.

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