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Human immunodeficiency virus (HIV) can adapt to an individual's T cell immune response via genomic mutations that affect antigen recognition and impact disease outcome. These viral adaptations are specific to the host's human leucocyte antigen (HLA) alleles, as these molecules determine which peptides are presented to T cells. As HLA molecules are highly polymorphic at the population level, horizontal transmission events are most commonly between HLA-mismatched donor/recipient pairs, representing new immune selection environments for the transmitted virus. In this study, we utilised a deep sequencing approach to determine the HIV quasispecies in 26 mother-to-child transmission pairs where the potential for founder viruses to be pre-adapted is high due to the pairs being haplo-identical at HLA loci. This scenario allowed the assessment of specific HIV adaptations following transmission in either a non-selective immune environment, due to recipient HLA mismatched to original selecting HLA, or a selective immune environment, mediated by matched donor/recipient HLA. We show that the pattern of reversion or fixation of HIV adaptations following transmission provides insight into the replicative cost, and likely compensatory networks, associated with specific adaptations in vivo. Furthermore, although transmitted viruses were commonly heavily pre-adapted to the child's HLA genotype, we found evidence of de novo post-transmission adaptation, representing new epitopes targeted by the child's T cell response. High-resolution analysis of HIV adaptation is relevant when considering vaccine and cure strategies for individuals exposed to adapted viruses via transmission or reactivated from reservoirs.
Pubmed ID: 31821379 RIS Download
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A collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsNIH genetic sequence database that provides annotated collection of all publicly available DNA sequences for almost 280 000 formally described species (Jan 2014) .These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. It is part of International Nucleotide Sequence Database Collaboration and daily data exchange with European Nucleotide Archive (ENA) and DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through NCBI Entrez retrieval system, which integrates data from major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of GenBank database are available by FTP.
View all literature mentionsA portal to the on-line prediction services at Center for Biological Sequence Analysis. All of the servers are available as interactive input forms, and most of the servers are also available as stand-alone software packages with the same functionality. Ready-to-ship packages exist for the most common UNIX platforms. In addition, for some servers, programmatic access is provided in the form of SOAP-based Web Services.
View all literature mentionsThe Stanford University HIV Drug Resistance Database is a curated public database designed to represent, store, and analyze the different forms of data underlying HIVs drug resistance. HIVDB has three main types of content: (1) Database queries and references, (2) Interactive programs, and (3) Educational resources. Database queries are designed primarily for researchers studying HIV drug resistance. The interactive programs and educational resources are designed for both researchers and those wishing to learn more about HIV drug resistance. 1.DATABASE QUERY AND REFERENCE PAGES Genotype-Treatment Correlations This Genotype-Treatment section of the database links to 15 interactive query pages that explore the relationship between treatment with HIV-1 antiretroviral drugs (ARVs) and mutations in HIV reverse transcriptase (RT), protease, and integrase. There are five types of interactive query pages: Treatment Profiles (Protease and RT inhibitors) Mutation Profiles (Protease and RT mutations) Detailed Treatment Queries (Protease, RT, and integrase inhibitors) Detailed Mutation Queries (Protease, RT, and integrase mutations) Mutation Prevalence According to Subtype and Treatment Genotype-Phenotype Correlations The main page of the Genotype-Phenotype Correlations section links to four interactive query pages: three dynamically updated data summaries and one regularly updated downloadable dataset. Drug Resistance Positions Query for levels of resistance associated with known drug resistance mutations Detailed Phenotype Queries Queries for levels of resistance associated with individual mutations or mutation combinations at all positions of protease, RT, and integrase Patterns of Drug Resistance Mutations Downloadable Reference Dataset Genotype-Clinical Correlations This part of the database has two main sections: Clinical Trials Datasets Summaries of Clinical Studies References This part of the database has two main sections: one with summaries of the data from each of the references in HIVDB and one in which every primate immunodeficiency virus sequence in GenBank is annotated according to its presence or absence in HIVDB. Studies in HIVDB GenBank <=> HIVDB New Submissions Approximately every three months, the New Submissions section lists the studies that have been entered into HIVDB. The study title links to the introductory page of the study in the References section. Database Statistics (http://hivdb.stanford.edu/pages/HIVdbStatistics.html) 2. INTERACTIVE PROGRAMS HIVDB has seven main interactive programs. 1. HIVdb Program Mutation List Analysis Sequence Analysis HIVdb Output Sierra Web Service Release Notes Algorithm Specification Interface (ASI) 2. HIValg Program 3. HIVseq Program 4. Calibrated Population Resistance (CPR) tool 5. Mutation ARV Evidence Listing (MARVEL) 6. ART-AiDE 7. Rega HIV-1 Subtyping tool Three programs in the HIV Drug Resistance Database share a common code base: HIVseq, HIVdb, and HIValg. HIVseq accepts user-submitted protease, RT, and integrase sequences, compares them to the consensus subtype B reference sequence, and uses the differences as query parameters for interrogating the HIV Drug Resistance database (Shafer, D Jung, & B Betts, Nat Med 2000; Rhee SY et al. AIDS 2006). The query result provides users with the prevalence of protease, RT and integrase mutations according to subtype and PI, nucleoside RT inhibitor (NRTI), non-nucleoside RT inhibitor (NNRTI), and integrase inhibitor (INI) exposure. This allows users to detect unusual sequence results immediately so that the person doing the sequencing can check the primary sequence output while it is still on the desktop. In addition, unexpected associations between sequences or isolates can be discovered by immediately retrieving data on isolates sharing one or more mutations with the sequence. There are three ways in which the HIVdb program can be used: (i) entering a list of protease and RT mutations, (ii) entering a complete sequence containing protease, RT, and/or integrase, and (iii) using a Web Service. HIVdb is an expert system that accepts user-submitted HIV-1 pol sequences and returns inferred levels of resistance to 20 FDA-approved ARV drugs including 8 PIs, 7 NRTIs, 4 NNRTIs, and - with this update - one INI. In the HIVdb system, each HIV-1 drug resistance mutation is assigned a drug penalty score and a comment; the total score for a drug is derived by adding the scores of each mutation associated with resistance to that drug. Using the total drug score, the program reports one of the following levels of inferred drug resistance: susceptible, potential low-level resistance, low-level resistance, intermediate resistance, and high-level resistance. HIValg is designed for users interested in comparing the results of different algorithms or who are interested in comparing and evaluating existing and newly developed algorithms. The ability to develop new algorithms that can be run on the HIV Drug Resistance Database depends on the Algorithm Specific Interface (ASI) compiler (Shafer & Betts JCM 2003). Submission of Sequences and Mutations For each of the three programs, sequences can be entered using either the Sequence Analysis Form or the Mutation List form. 3. EDUCATIONAL RESOURCES HIVDB contains several regularly updated sections summarizing data linking RT, protease, and integrase mutations and antiretroviral drugs (ARVs). These sections include (i) tabular summaries of the major mutations associated with each ARV class, (ii) detailed summaries of the major, minor, and accessory mutations associated with each ARV, (iii) the comments used by the HIVdb program, (iv) the scores used by the HIVdb program, (v) clinical studies in which baseline drug resistance mutations have been correlated with the virological response (clinical outcome) to a specific ARV, (vi) mutations that can be used for drug resistance surveillance, and (vii) a two-page PDF handout. 1. Drug Resistance Summaries Tabular Drug Resistance Summaries by ARV Class Detailed Drug Resistance Summaries by ARV Drug Resistance Mutation Comments Used by the HIVdb Program Drug Resistance Mutation Scores Used by the HIVdb Program Genotype-Clinical Outcome Correlation Studies 2. Surveillance Drug-Resistance Mutation List Section 3. PDF Handout Grant Support 1. National Institute for Allergy and Infectious Diseases (NIAID, NIH): Online HIV Drug Resistance Database (PI: Robert W. Shafer, MD, 1R01AI68581-01A1), 04/01/06 - 3/31/11 2. National Institute for Allergy and Infectious Diseases (NIAID, NIH) supplement to the grant Identification of Multidrug-Resistant HIV-1 Isolates (PI: Robert W. Shafer, MD, AI46148-01): Supplement provided 1999-2005. 3. NIH/NIGMS Program Project on AIDS Structural Biology Program Project: Targeting Ensembles of Drug Resistant Protease Variants (PI: Celia Schiffer, PhD, University of Massachusetts): 2002-2007 4. University-wide AIDS Research Program (CR03-ST-524). Community collaborative award: Optimizing Clinical HIV Genotypic Resistance Interpretation: Principal Investigators: Robert W. Shafer, MD and W. Jeffrey Fessel MD (Kaiser Permanente Medical Care Program): 2004-2005 5. Stanford University Bio-X Interdisciplinary Initiative: HIV Gene Sequence Analysis for Drug Resistance Studies: A Pharmacogenetic Challenge Principal Investigators: Robert W. Shafer, MD and Daphne Koller, Ph.D. (Computer Science): 2000-2002
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsLos Alamos National Laboratory is a premier national security research institution, delivering scientific and engineering solutions for the nation''s most crucial and complex problems. Our primary responsibility is ensuring the safety, security, and reliability of the nation''s nuclear deterrent. The Los Alamos of today emphasizes worker safety, effective operational safeguards & security, and environmental stewardship, while outstanding science remains the foundation of the Laboratory. In addition to supporting the Lab''s core national security mission, our work advances bioscience, chemistry, computer science, earth and environmental sciences, materials science, and physics disciplines.
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