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Sample records for alamos hiv sequence

  1. HIV Sequence Compendium 2015

    SciTech Connect

    Foley, Brian Thomas; Leitner, Thomas Kenneth; Apetrei, Cristian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette Tina Marie

    2015-10-05

    This compendium is an annual printed summary of the data contained in the HIV sequence database. We try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2015. Hence, though it is published in 2015 and called the 2015 Compendium, its contents correspond to the 2014 curated alignments on our website. The number of sequences in the HIV database is still increasing. In total, at the end of 2014, there were 624,121 sequences in the HIV Sequence Database, an increase of 7% since the previous year. This is the first year that the number of new sequences added to the database has decreased compared to the previous year. The number of near complete genomes (>7000 nucleotides) increased to 5834 by end of 2014. However, as in previous years, the compendium alignments contain only a fraction of these. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/ content/sequence/NEWALIGN/align.html As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  2. HIV Sequence Compendium 2010

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Leitner, Thomas; Apetrei, Christian; Hahn, Beatrice; Mizrachi, Ilene; Mullins, James; Rambaut, Andrew; Wolinsky, Steven; Korber, Bette

    2010-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Each of the alignments attempts to display the genetic variability within the different species, groups and subtypes of the virus. This compendium contains sequences published before January 1, 2010. Hence, though it is called the 2010 Compendium, its contents correspond to the 2009 curated alignments on our website. The number of sequences in the HIV database is still increasing exponentially. In total, at the time of printing, there were 339,306 sequences in the HIV Sequence Database, an increase of 45% since last year. The number of near complete genomes (>7000 nucleotides) increased to 2576 by end of 2009, reflecting a smaller increase than in previous years. However, as in previous years, the compendium alignments contain only a small fraction of these. Included in the alignments are a small number of sequences representing each of the subtypes and the more prevalent circulating recombinant forms (CRFs) such as 01 and 02, as well as a few outgroup sequences (group O and N and SIV-CPZ). Of the rarer CRFs we included one representative each. A more complete version of all alignments is available on our website, http://www.hiv.lanl.gov/content/sequence/NEWALIGN/align.html. Reprints are available from our website in the form of both HTML and PDF files. As always, we are open to complaints and suggestions for improvement. Inquiries and comments regarding the compendium should be addressed to seq-info@lanl.gov.

  3. HIV sequence compendium 2002

    SciTech Connect

    Kuiken, Carla; Foley, Brian; Freed, Eric; Hahn, Beatrice; Marx, Preston; McCutchan, Francine; Mellors, John; Wolinsky, Steven; Korber, Bette

    2002-12-31

    This compendium is an annual printed summary of the data contained in the HIV sequence database. In these compendia we try to present a judicious selection of the data in such a way that it is of maximum utility to HIV researchers. Traditionally, we present the sequence data themselves in the form of alignments: Section II, an alignment of a selection of HIV-1/SIVcpz full-length genomes (a lot of LAI-like sequences, for example, have been omitted because they are so similar that they bias the alignment); Section III, a combined HIV-1/HIV-2/SIV whole genome alignment; Sections IV–VI, amino acid alignments for HIV-1/SIV-cpz, HIV-2/SIV, and SIVagm. The HIV-2/SIV and SIVagm amino acid alignments are separate because the genetic distances between these groups are so great that presenting them in one alignment would make it very elongated because of the large number of gaps that have to be inserted. As always, tables with extensive background information gathered from the literature accompany the whole genome alignments. The collection of whole-gene sequences in the database is now large enough that we have abundant representation of most subtypes. For many subtypes, and especially for subtype B, a large number of sequences that span entire genes were not included in the printed alignments to conserve space. A more complete version of all alignments is available on our website, http://hiv-web.lanl.gov/content/hiv-db/ALIGN_CURRENT/ALIGN-INDEX.html. Importantly, all these alignments have been edited to include only one sequence per person, based on phylogenetic trees that were created for all of them, as well as on the literature. Because of the number of sequences available, we have decided to use a different selection principle this year, based on the epidemiological importance of the subtypes. Subtypes A–D and CRFs 01 and 02 are by far the most widespread variants, and for these (when available) we have included 8–10 representatives in the alignments. The other

  4. HIV-1 Sequence Data Coverage in Central East Africa from 1959 to 2013.

    PubMed

    Lamers, Susanna L; Barbier, Andrew E; Ratmann, Oliver; Fraser, Christophe; Rose, Rebecca; Laeyendecker, Oliver; Grabowski, Mary K

    2016-09-01

    Central and Eastern African HIV sequence data have been most critical in understanding the establishment and evolution of the global HIV pandemic. Here we report on the extent of publicly available HIV genetic sequence data in the Los Alamos National Laboratory Sequence Database sampled from 1959 to 2013 from six African countries: Uganda, Kenya, Tanzania, Burundi, the Democratic Republic of Congo, and Rwanda. We have summarized these data, including HIV subtypes, the years sampled, and the genomic regions sequenced. We also provide curated alignments for this important geographic area in five HIV genomic regions with substantial coverage. PMID:27353049

  5. Los Alamos hepatitis C virus sequence and human immunology databases: an expanding resource for antiviral research.

    PubMed

    Hraber, Peter T; Leach, Robert W; Reilly, Lee P; Thurmond, James; Yusim, Karina; Kuiken, Carla

    2007-01-01

    The hepatitis C virus (HCV) resource at Los Alamos (hcv.lanl.gov) provides access to multiple databases: one containing annotated sequences and the other a repository of immunogenic epitopes. They are derived from databases originally developed for HIV research (hiv.lanl.gov). HCV and HIV are RNA viruses with relatively compact genomes (around 10 kb) that are extraordinarily variable, both within and between hosts. This diversity requires methods to track and exclude variants from an individual infection or from epidemiologically related infections, and tools to analyse the variation. The HCV immunology database contains a curated inventory of immunogenic epitopes and information about their interaction with the host immune system, with associated retrieval and analysis tools. This interactive resource provides flexible retrieval tools for sequences, epitopes, clinical information, and meta-data, as well as utilities for scientific data analysis, to investigators with internet access and a web browser. This paper describes the types of data and the services that these databases offer, the tools they provide, and their configuration and use. Examples of applications to clonal analysis for drug-resistance mutations are shown.

  6. Integrated sequence and immunology filovirus database at Los Alamos

    PubMed Central

    Yoon, Hyejin; Foley, Brian; Feng, Shihai; Macke, Jennifer; Dimitrijevic, Mira; Abfalterer, Werner; Szinger, James; Fischer, Will; Kuiken, Carla; Korber, Bette

    2016-01-01

    The Ebola outbreak of 2013–15 infected more than 28 000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. As this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy. Database URL: www.hfv.lanl.gov PMID:27103629

  7. Integrated sequence and immunology filovirus database at Los Alamos

    SciTech Connect

    Yusim, Karina; Yoon, Hyejin; Foley, Brian; Feng, Shihai; Macke, Jennifer; Dimitrijevic, Mira; Abfalterer, Werner; Szinger, James; Fischer, Will; Kuiken, Carla; Korber, Bette

    2016-01-01

    The Ebola outbreak of 2013–15 infected more than 28,000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. We report that as this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.

  8. Integrated sequence and immunology filovirus database at Los Alamos

    DOE PAGES

    Yusim, Karina; Yoon, Hyejin; Foley, Brian; Feng, Shihai; Macke, Jennifer; Dimitrijevic, Mira; Abfalterer, Werner; Szinger, James; Fischer, Will; Kuiken, Carla; et al

    2016-01-01

    The Ebola outbreak of 2013–15 infected more than 28,000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. We report that as this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of knownmore » natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.« less

  9. A relational database system for the maintenance and verification of the Los Alamos sequence library.

    PubMed Central

    Kanehisa, M; Fickett, J W; Goad, W B

    1984-01-01

    The nucleic acid sequence databases of Los Alamos National Laboratory, European Molecular Biology Laboratory, and others are organized in a single relational database. This organization with a suitable relational database management program facilitates the tasks of reporting statistics, making cross-references, and double-checking of the original databases. PMID:6694899

  10. Integrated sequence and immunology filovirus database at Los Alamos.

    PubMed

    Yusim, Karina; Yoon, Hyejin; Foley, Brian; Feng, Shihai; Macke, Jennifer; Dimitrijevic, Mira; Abfalterer, Werner; Szinger, James; Fischer, Will; Kuiken, Carla; Korber, Bette

    2016-01-01

    The Ebola outbreak of 2013-15 infected more than 28 000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. As this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family ITALIC! Filoviridaesequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.Database URL:www.hfv.lanl.gov. PMID:27103629

  11. A Pan-HIV Strategy for Complete Genome Sequencing

    PubMed Central

    Yamaguchi, Julie; Alessandri-Gradt, Elodie; Tell, Robert W.; Brennan, Catherine A.

    2015-01-01

    Molecular surveillance is essential to monitor HIV diversity and track emerging strains. We have developed a universal library preparation method (HIV-SMART [i.e., switching mechanism at 5′ end of RNA transcript]) for next-generation sequencing that harnesses the specificity of HIV-directed priming to enable full genome characterization of all HIV-1 groups (M, N, O, and P) and HIV-2. Broad application of the HIV-SMART approach was demonstrated using a panel of diverse cell-cultured virus isolates. HIV-1 non-subtype B-infected clinical specimens from Cameroon were then used to optimize the protocol to sequence directly from plasma. When multiplexing 8 or more libraries per MiSeq run, full genome coverage at a median ∼2,000× depth was routinely obtained for either sample type. The method reproducibly generated the same consensus sequence, consistently identified viral sequence heterogeneity present in specimens, and at viral loads of ≤4.5 log copies/ml yielded sufficient coverage to permit strain classification. HIV-SMART provides an unparalleled opportunity to identify diverse HIV strains in patient specimens and to determine phylogenetic classification based on the entire viral genome. Easily adapted to sequence any RNA virus, this technology illustrates the utility of next-generation sequencing (NGS) for viral characterization and surveillance. PMID:26699702

  12. Molecular Characterization of Mexican HIV-1 Vif Sequences.

    PubMed

    Guerra-Palomares, Sandra E; Hernandez-Sanchez, Pedro G; Esparza-Perez, Mario A; Arguello, J Rafael; Noyola, Daniel E; Garcia-Sepulveda, Christian A

    2016-03-01

    The viral infectivity factor (Vif) is an HIV accessory protein that counteracts host antiviral proteins of the APOBEC3 family. Accumulating evidence highlights the pivotal role that accessory HIV proteins have on disease pathogenesis, a fact that has made them targets of interest for novel therapeutic and preventive strategies. Little is known about Vif sequence diversity outside of African or white populations. Mexico is home to Americas' third largest HIV-affected population and Mexican Hispanics represent an ever-increasing U.S. minority. This study provides a detailed analysis of the diversity seen in 77 Mexican Vif protein sequences. Phylogenetic analysis shows that most sequences cluster with HIV-1 subtype B, while less than 10% exhibit greater similarity to subtype D and A subtypes. Although most functional motifs are conserved among the Mexican sequences, substantial diversity was seen in some APOBEC binding sites, the nuclear localization inhibitory signal, and the CBFβ interaction sites.

  13. Deep sequencing of HIV: clinical and research applications.

    PubMed

    Chabria, Shiven B; Gupta, Shaili; Kozal, Michael J

    2014-01-01

    Human immunodeficiency virus (HIV) exhibits remarkable diversity in its genomic makeup and exists in any given individual as a complex distribution of closely related but nonidentical genomes called a viral quasispecies, which is subject to genetic variation, competition, and selection. This viral diversity clinically manifests as a selection of mutant variants based on viral fitness in treatment-naive individuals and based on drug-selective pressure in those on antiretroviral therapy (ART). The current standard-of-care ART consists of a combination of antiretroviral agents, which ensures maximal viral suppression while preventing the emergence of drug-resistant HIV variants. Unfortunately, transmission of drug-resistant HIV does occur, affecting 5% to >20% of newly infected individuals. To optimize therapy, clinicians rely on viral genotypic information obtained from conventional population sequencing-based assays, which cannot reliably detect viral variants that constitute <20% of the circulating viral quasispecies. These low-frequency variants can be detected by highly sensitive genotyping methods collectively grouped under the moniker of deep sequencing. Low-frequency variants have been correlated to treatment failures and HIV transmission, and detection of these variants is helping to inform strategies for vaccine development. Here, we discuss the molecular virology of HIV, viral heterogeneity, drug-resistance mutations, and the application of deep sequencing technologies in research and the clinical care of HIV-infected individuals. PMID:24821496

  14. Performance of genotypic tools for prediction of tropism in HIV-1 subtype C V3 loop sequences.

    PubMed

    Gupta, Soham; Neogi, Ujjwal; Srinivasa, Hiresave; Shet, Anita

    2015-01-01

    Currently, there is no consensus on the genotypic tools to be used for tropism analysis in HIV-1 subtype C strains. Thus, the aim of the study was to evaluate the performance of the different V3 loop-based genotypic algorithms available. We compiled a dataset of 645 HIV-1 subtype C V3 loop sequences of known coreceptor phenotypes (531 R5-tropic/non-syncytium-inducing and 114 X4-tropic/R5X4-tropic/syncytium-inducing sequences) from the Los Alamos database (http://www.hiv.lanl.gov/) and previously published literature. Coreceptor usage was predicted based on this dataset using different software-based machine-learning algorithms as well as simple classical rules. All the sophisticated machine-learning methods showed a good concordance of above 85%. Geno2Pheno (false-positive rate cutoff of 5-15%) and CoRSeqV3-C were found to have a high predicting capability in determining both HIV-1 subtype C X4-tropic and R5-tropic strains. The current sophisticated genotypic tropism tools based on V3 loop perform well for tropism prediction in HIV-1 subtype C strains and can be used in clinical settings. PMID:25573618

  15. Dynamics of immunoglobulin sequence diversity in HIV-1 infected individuals

    PubMed Central

    Hoehn, Kenneth B.; Gall, Astrid; Bashford-Rogers, Rachael; Fidler, S. J.; Kaye, S.; Weber, J. N.; McClure, M. O.; Kellam, Paul; Pybus, Oliver G.

    2015-01-01

    Advances in immunoglobulin (Ig) sequencing technology are leading to new perspectives on immune system dynamics. Much research in this nascent field has focused on resolving immune responses to viral infection. However, the dynamics of B-cell diversity in early HIV infection, and in response to anti-retroviral therapy, are still poorly understood. Here, we investigate these dynamics through bulk Ig sequencing of samples collected over 2 years from a group of eight HIV-1 infected patients, five of whom received anti-retroviral therapy during the first half of the study period. We applied previously published methods for visualizing and quantifying B-cell sequence diversity, including the Gini index, and compared their efficacy to alternative measures. While we found significantly greater clonal structure in HIV-infected patients versus healthy controls, within HIV patients, we observed no significant relationships between statistics of B-cell clonal expansion and clinical variables such as viral load and CD4+ count. Although there are many potential explanations for this, we suggest that important factors include poor sampling resolution and complex B-cell dynamics that are difficult to summarize using simple summary statistics. Importantly, we find a significant association between observed Gini indices and sequencing read depth, and we conclude that more robust analytical methods and a closer integration of experimental and theoretical work is needed to further our understanding of B-cell repertoire diversity during viral infection. PMID:26194755

  16. Computer analysis of HIV epitope sequences

    SciTech Connect

    Gupta, G.; Myers, G.

    1990-01-01

    Phylogenetic tree analysis provide us with important general information regarding the extent and rate of HIV variation. Currently we are attempting to extend computer analysis and modeling to the V3 loop of the type 2 virus and its simian homologues, especially in light of the prominent role the latter will play in animal model studies. Moreover, it might be possible to attack the slightly similar V4 loop by this approach. However, the strategy relies very heavily upon natural'' information and constraints, thus there exist severe limitations upon the general applicability, in addition to uncertainties with regard to long-range residue interactions. 5 refs., 3 figs.

  17. APOBEC3H Haplotypes and HIV-1 Pro-Viral vif DNA Sequence Diversity in Early Untreated HIV-1 Infection

    PubMed Central

    Gourraud, PA; Karaouni, A; Woo, JM; Schmidt, T; Oksenberg, JR; Hecht, FM; Liegler, TJ; Barbour, JD

    2011-01-01

    We examined single nucleotide polymorphisms (SNP) in the APOBEC3 locus on chromosome 22, paired to population sequences of pro-viral HIV-1 vif of peripheral blood mononuclear cells (PBMC), from 96 recently HIV-1 infected treatment naïve adults. We found evidence for the existence of an APOBEC3H linkage disequilibrium (LD) block associated with variation in GA->AA, or APOBEC3F signature, sequence changes in pro-viral HIV-1 vif sequence (top significant 10 SNPs with a top-significant p=4.8×10−3). We identified a common 5 position risk haplotype distal to APOBEC3H (A3Hrh). These markers were in high LD (D′ = 1; r2=0.98) to a previously described A3H ‘RED’ haplotype containing a variant (E121) with enhanced susceptibility to HIV-1 Vif (Zhen et al 2009 [1]). This association is confirmed by a haplotype analysis: Homozygote carriers of the A3Hrh had lower GA->AA (A3F) sequence editing on pro-viral HIV-1 vif sequence (p = 0.01), and lower HIV-1 RNA levels over time during early, untreated HIV-1 infection, (p = 0.015 mixed effects model). This effect may be due to enhanced susceptibility of A3H forms to HIV-1 Vif mediated viral suppression of sequence editing activity, slowing viral diversification and escape from immune responses. PMID:21167246

  18. [HIV-1 subtype distribution determined by phylogenetic analysis of pol gene sequences and automated subtyping tools among HIV-1 isolates from the Aegian Region of Turkey].

    PubMed

    Uluer Biçeroğlu, Servet; Altuğlu, Imre; Nazli Zeka, Arzu; Gökengin, Deniz; Yazan Sertöz, Rüçhan

    2014-07-01

    Human immunodeficiency virus (HIV) exhibiting remarkable genetic variability, includes two genotypes namely HIV-1 (group M, N, O and P) and HIV-2 (group A-H). HIV-1 group M, which is mainly the cause of the AIDS pandemic, is divided into nine pure subtypes, more than 45 circulating recombinant forms (CRF) and numerous unique recombinant forms (URF). According to the documents of Turkish Government of Health, among a total of 6802 HIV-positive cases, 1096 of them were defined as AIDS as of June 2013 in Turkey. Although subtype B is the predominant subtype, recent studies indicate higher proportion of CRFs similar to their increasing role in the HIV pandemic. The aim of this study was to determine the subtype distribution of HIV-1 strains isolated from 70 patients (61 male, 9 female; age range: 16-73 yrs, mean age: 39.6 yrs) who presented to our institution between April 2008-June 2013. HIV-1 strains were subtyped by phylogenetic analysis of the pol gene region and commonly used automated subtyping tools namely, Stanford HIV db v6.2.0 and Rega v3.0. Pol sequences retrieved from the Los Alamos database and from GeneBank, were trimmed from full-length genomes. Phylogenetic analysis of the 1302 base pair of the pol gene region was performed using Mega v5.2 software. The sequences were aligned using Muscle and phylogenetic distances between sequences were estimated by using Kimura two-parameter model (transition/transversion ratio: 2.0). Tree topology was obtained using neighbour-joining method and bootstrap value was set at 1000. Sixty-one (87.1%) patients were antiretroviral treatment (ART)-naive and nine were on different ART regimens. The subtypes of the isolates according to phylogenetic analysis were found as follows; 31 (44.2%) subtype B, 24 (34.2%) CRF42_BF, 6 (8.5%) B/CRF02_AG recombinants, 5 (7.1%) sub-subtype A1, 1 (1.4%) sub-subtype F1, 1 (%1.4) CRF 25_cpx, 1 (1.4%) CRF02_AG and 1 (1.4%) CRF01_AE. Rega v3.0 subtyping tool produced five discrepant results (4 B

  19. Deep Sequencing of the Vaginal Microbiota of Women with HIV

    PubMed Central

    Hummelen, Ruben; Fernandes, Andrew D.; Macklaim, Jean M.; Dickson, Russell J.; Changalucha, John

    2010-01-01

    Background Women living with HIV and co-infected with bacterial vaginosis (BV) are at higher risk for transmitting HIV to a partner or newborn. It is poorly understood which bacterial communities constitute BV or the normal vaginal microbiota among this population and how the microbiota associated with BV responds to antibiotic treatment. Methods and Findings The vaginal microbiota of 132 HIV positive Tanzanian women, including 39 who received metronidazole treatment for BV, were profiled using Illumina to sequence the V6 region of the 16S rRNA gene. Of note, Gardnerella vaginalis and Lactobacillus iners were detected in each sample constituting core members of the vaginal microbiota. Eight major clusters were detected with relatively uniform microbiota compositions. Two clusters dominated by L. iners or L. crispatus were strongly associated with a normal microbiota. The L. crispatus dominated microbiota were associated with low pH, but when L. crispatus was not present, a large fraction of L. iners was required to predict a low pH. Four clusters were strongly associated with BV, and were dominated by Prevotella bivia, Lachnospiraceae, or a mixture of different species. Metronidazole treatment reduced the microbial diversity and perturbed the BV-associated microbiota, but rarely resulted in the establishment of a lactobacilli-dominated microbiota. Conclusions Illumina based microbial profiling enabled high though-put analyses of microbial samples at a high phylogenetic resolution. The vaginal microbiota among women living with HIV in Sub-Saharan Africa constitutes several profiles associated with a normal microbiota or BV. Recurrence of BV frequently constitutes a different BV-associated profile than before antibiotic treatment. PMID:20711427

  20. HIV Integration Site Analysis of Cellular Models of HIV Latency with a Probe-Enriched Next-Generation Sequencing Assay

    PubMed Central

    Sunshine, Sara; Kirchner, Rory; Amr, Sami S.; Mansur, Leandra; Shakhbatyan, Rimma; Kim, Michelle; Bosque, Alberto; Siliciano, Robert F.; Planelles, Vicente; Hofmann, Oliver; Ho Sui, Shannan

    2016-01-01

    ABSTRACT Antiretroviral therapy (ART) is successful in the suppression of HIV but cannot target and eradicate the latent proviral reservoir. The location of retroviral integration into the human genome is thought to play a role in the clonal expansion of infected cells and HIV persistence. We developed a high-throughput targeted sequence capture assay that uses a pool of HIV-specific probes to enrich Illumina libraries prior to deep sequencing. Using an expanded clonal population of ACH-2 cells, we demonstrate that this sequence capture assay has an extremely low false-positive rate. This assay assessed four cellular models commonly used to study HIV latency and latency-reversing agents: ACH-2 cells, J-Lat cells, the Bcl-2-transduced primary CD4+ model, and the cultured TCM (central memory) CD4+ model. HIV integration site characteristics and genes were compared between these cellular models and to previously reported patient data sets. Across these cellular models, there were significant differences in integration site characteristics, including orientation relative to that of the host gene, the proportion of clonally expanded sites, and the proportion located within genic regions and exons. Despite a greater diversity of minority integration sites than expected in ACH-2 cells, their integration site characteristics consistently differed from those of the other models and from the patient samples. Gene ontology analysis of highly represented genes from the patient samples found little overlap with HIV-containing genes from the cell lines. These findings show that integration site differences exist among the commonly used cellular models of HIV latency and in comparison to integration sites found in patient samples. IMPORTANCE Despite the success of ART, currently there is no successful therapy to eradicate integrated proviruses. Cellular models of HIV latency are used to test the efficacy of latency-reversing agents, but it is unclear how well these models reflect

  1. Identification of HIV-1 Genitourinary Tract Compartmentalization by Analyzing the env Gene Sequences in Urine

    PubMed Central

    BLASI, Maria; CARPENTER, J. Harris; BALAKUMARAN, Bala; CARA, Andrea; GAO, Feng; KLOTMAN, Mary E.

    2015-01-01

    Objective HIV-1 persists indefinitely in memory CD4+ T cells and other long-lived cellular reservoirs despite antiretroviral therapy (ART). Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that the kidney represents a separate compartment for HIV-1 replication. Here, to better understand the viruses in this unique site, we genetically characterized and compared the viruses in blood and urine specimens from twenty-four HIV-1 infected subjects with detectable viremia. Design and Methods Blood and urine samples were obtained from 35 HIV-1 positive subjects. Single-genome amplification was performed on HIV-1 env RNA and DNA isolated from urine supernatants and urine derived cell pellets respectively, as well as from plasma and PBMC from the same individuals. Neighbor-joining trees were constructed under the Kimura 2-parameter mode. Results We amplified and sequenced the full-length HIV-1 envelope (env) gene from twelve of the twenty-four individuals, indicating that fifty percent (50%) of the viremic HIV-1 positive patients had viral RNA in their urine. Phylogenetic analysis of the env sequences from four subjects with more than fifteen urine-derived env sequences showed that the majority of the sequences from urine formed distinct cluster(s) independent of those PBMC and plasma-derived sequences, consistent with viral compartmentalization in the urine. Conclusions Our results suggest the presence of a distinct HIV compartment in the genitourinary tract. PMID:26372275

  2. Performance Characteristics of the TRUGENE HIV-1 Genotyping Kit and the Opengene DNA Sequencing System

    PubMed Central

    Kuritzkes, Daniel R.; Grant, Robert M.; Feorino, Paul; Griswold, Marshal; Hoover, Marie; Young, Russell; Day, Stephen; Lloyd, Jr., Robert M.; Reid, Caroline; Morgan, Gillian F.; Winslow, Dean L.

    2003-01-01

    The TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System are designed to sequence the protease (PR)- and reverse transcriptase (RT)-coding regions of human immunodeficiency virus type 1 (HIV-1) pol. Studies were undertaken to determine the accuracy of this assay system in detecting resistance-associated mutations and to determine the effects of RNA extraction methods, anticoagulants, specimen handling, and potentially interfering substances. Samples were plasma obtained from HIV-infected subjects or seronegative plasma to which viruses derived from wild-type and mutant infectious molecular clones (IMC) of HIV-1 were added. Extraction methods tested included standard and UltraSensitive AMPLICOR HIV-1 MONITOR, QIAGEN viral RNA extraction mini kit, and QIAGEN Ultra HIV extraction kit, and NASBA manual HIV-1 quantitative NucliSens. Sequence data from test sites were compared to a “gold standard” reference sequence to determine the percent agreement. Comparisons between test and reference sequences at the nucleotide level showed 97.5 to 100% agreement. Similar results were obtained regardless of extraction method, regardless of use of EDTA or acid citrate dextrose as anticoagulant, and despite the presence of triglycerides, bilirubin, hemoglobin, antiretroviral drugs, HIV-2, hepatitis C virus (HCV), HBV, cytomegalovirus, human T-cell leukemia virus type 1 (HTLV-1), or HTLV-2. Samples with HIV-1 RNA titers of ≥1,000 copies/ml gave consistent results. The TRUGENE HIV-1 Genotyping Kit and OpenGene DNA Sequencing System consistently generate highly accurate sequence data when tested with IMC-derived HIV and patient samples. PMID:12682150

  3. Trajectories of Childbearing among HIV Infected Indian Women: A Sequence Analysis Approach

    PubMed Central

    Darak, Shrinivas; Mills, Melinda; Kulkarni, Vinay; Kulkarni, Sanjeevani; Hutter, Inge; Janssen, Fanny

    2015-01-01

    Background HIV infection closely relates to and deeply affects the reproductive career of those infected. However, little is known about the reproductive career trajectories, specifically the interaction of the timing of HIV diagnosis with the timing and sequencing of reproductive events among HIV infected women. This is the first study to describe and typify this interaction. Methods Retrospective calendar data of ever married HIV infected women aged 15-45 attending a HIV clinic in Pune, Maharashtra, Western India (N=622) on reproductive events such as marriage, cohabitation with the partner, use of contraception, pregnancy, childbirth and HIV diagnosis were analyzed using sequence analysis and multinomial logistic regression. Results Optimal matching revealed three distinct trajectories: 1) HIV diagnosis concurrent with childbearing (40.7%), 2) HIV diagnosis after childbearing (32.1%), and 3) HIV diagnosis after husband’s death (27.2%). Multinomial logistic regression (trajectory 1 = baseline) showed that women who got married before the age of 21 years and who had no or primary level education had a significantly higher risk of knowing their HIV status either after childbearing or close to their husband’s death. The risk of HIV diagnosis after husband’s death was also higher among rural women and those who were diagnosed before 2005. Conclusions Three distinct patterns of interaction of timing of HIV diagnosis with timing and sequencing of events in the reproductive career were observed that have clear implications for (i) understanding of the individual life planning process in the context of HIV, (ii) formulation of assumptions for estimating HIV infected women in need of PMTCT services, and (iii) provision of care services. PMID:25906185

  4. Quantifying Next Generation Sequencing Sample Pre-Processing Bias in HIV-1 Complete Genome Sequencing.

    PubMed

    Vrancken, Bram; Trovão, Nídia Sequeira; Baele, Guy; van Wijngaerden, Eric; Vandamme, Anne-Mieke; van Laethem, Kristel; Lemey, Philippe

    2016-01-01

    Genetic analyses play a central role in infectious disease research. Massively parallelized "mechanical cloning" and sequencing technologies were quickly adopted by HIV researchers in order to broaden the understanding of the clinical importance of minor drug-resistant variants. These efforts have, however, remained largely limited to small genomic regions. The growing need to monitor multiple genome regions for drug resistance testing, as well as the obvious benefit for studying evolutionary and epidemic processes makes complete genome sequencing an important goal in viral research. In addition, a major drawback for NGS applications to RNA viruses is the need for large quantities of input DNA. Here, we use a generic overlapping amplicon-based near full-genome amplification protocol to compare low-input enzymatic fragmentation (Nextera™) with conventional mechanical shearing for Roche 454 sequencing. We find that the fragmentation method has only a modest impact on the characterization of the population composition and that for reliable results, the variation introduced at all steps of the procedure--from nucleic acid extraction to sequencing--should be taken into account, a finding that is also relevant for NGS technologies that are now more commonly used. Furthermore, by applying our protocol to deep sequence a number of pre-therapy plasma and PBMC samples, we illustrate the potential benefits of a near complete genome sequencing approach in routine genotyping. PMID:26751471

  5. Near full-length HIV type 1M genomic sequences from Cameroon

    PubMed Central

    Tongo, Marcel; Dorfman, Jeffrey R.; Abrahams, Melissa-Rose; Mpoudi-Ngole, Eitel; Burgers, Wendy A.; Martin, Darren P.

    2015-01-01

    Background: Cameroon is the country in which HIV-1 group M (HIV-1M) likely originated and is today a major hotspot of HIV-1M genetic diversity. It remains unclear, however, whether the highly divergent HIV-1M lineages found in this country arose during the earliest phases of the global HIV-1M epidemic, or whether they arose more recently as a result of recombination events between globally circulating HIV-1M lineages. Methodology: To differentiate between these two possibilities, we performed phylogenetic analyses of the near full genome sequences of nine newly sequenced divergent HIV-1M isolates and 15 previously identified, apparently unique recombinant forms (URFs) from Cameroon. Results: Although two of the new genome sequences were clearly classifiable within subtype G, the remaining seven were highly divergent and phylogenetically branched either outside of, or very near the bases of clades containing the well characterised globally circulating viral lineages that they were most closely related to. Recombination analyses further revealed that these divergent viruses were likely complex URFs. We show, however that substantial portions (>1 Kb) of three of the new genome sequences and 15 of the previously characterised Cameroonian URFs have apparently been derived from divergent parental viruses that branch phylogenetically near the bases of the major HIV-1M clades. Conclusions and implications: Our analyses indicate the presence in Cameroon of contemporary descendants of numerous early-diverging HIV-1M lineages. Further efforts to sample and sequence viruses from such lineages could be crucial both for retracing the earliest evolutionary steps during the emergence of HIV-1M in humans, and accurately reconstructing the ancestral sequences of the major globally circulating HIV-1M lineages. PMID:26354000

  6. Quantifying Next Generation Sequencing Sample Pre-Processing Bias in HIV-1 Complete Genome Sequencing

    PubMed Central

    Vrancken, Bram; Trovão, Nídia Sequeira; Baele, Guy; van Wijngaerden, Eric; Vandamme, Anne-Mieke; van Laethem, Kristel; Lemey, Philippe

    2016-01-01

    Genetic analyses play a central role in infectious disease research. Massively parallelized “mechanical cloning” and sequencing technologies were quickly adopted by HIV researchers in order to broaden the understanding of the clinical importance of minor drug-resistant variants. These efforts have, however, remained largely limited to small genomic regions. The growing need to monitor multiple genome regions for drug resistance testing, as well as the obvious benefit for studying evolutionary and epidemic processes makes complete genome sequencing an important goal in viral research. In addition, a major drawback for NGS applications to RNA viruses is the need for large quantities of input DNA. Here, we use a generic overlapping amplicon-based near full-genome amplification protocol to compare low-input enzymatic fragmentation (Nextera™) with conventional mechanical shearing for Roche 454 sequencing. We find that the fragmentation method has only a modest impact on the characterization of the population composition and that for reliable results, the variation introduced at all steps of the procedure—from nucleic acid extraction to sequencing—should be taken into account, a finding that is also relevant for NGS technologies that are now more commonly used. Furthermore, by applying our protocol to deep sequence a number of pre-therapy plasma and PBMC samples, we illustrate the potential benefits of a near complete genome sequencing approach in routine genotyping. PMID:26751471

  7. Use of four next-generation sequencing platforms to determine HIV-1 coreceptor tropism.

    PubMed

    Archer, John; Weber, Jan; Henry, Kenneth; Winner, Dane; Gibson, Richard; Lee, Lawrence; Paxinos, Ellen; Arts, Eric J; Robertson, David L; Mimms, Larry; Quiñones-Mateu, Miguel E

    2012-01-01

    HIV-1 coreceptor tropism assays are required to rule out the presence of CXCR4-tropic (non-R5) viruses prior treatment with CCR5 antagonists. Phenotypic (e.g., Trofile™, Monogram Biosciences) and genotypic (e.g., population sequencing linked to bioinformatic algorithms) assays are the most widely used. Although several next-generation sequencing (NGS) platforms are available, to date all published deep sequencing HIV-1 tropism studies have used the 454™ Life Sciences/Roche platform. In this study, HIV-1 co-receptor usage was predicted for twelve patients scheduled to start a maraviroc-based antiretroviral regimen. The V3 region of the HIV-1 env gene was sequenced using four NGS platforms: 454™, PacBio® RS (Pacific Biosciences), Illumina®, and Ion Torrent™ (Life Technologies). Cross-platform variation was evaluated, including number of reads, read length and error rates. HIV-1 tropism was inferred using Geno2Pheno, Web PSSM, and the 11/24/25 rule and compared with Trofile™ and virologic response to antiretroviral therapy. Error rates related to insertions/deletions (indels) and nucleotide substitutions introduced by the four NGS platforms were low compared to the actual HIV-1 sequence variation. Each platform detected all major virus variants within the HIV-1 population with similar frequencies. Identification of non-R5 viruses was comparable among the four platforms, with minor differences attributable to the algorithms used to infer HIV-1 tropism. All NGS platforms showed similar concordance with virologic response to the maraviroc-based regimen (75% to 80% range depending on the algorithm used), compared to Trofile (80%) and population sequencing (70%). In conclusion, all four NGS platforms were able to detect minority non-R5 variants at comparable levels suggesting that any NGS-based method can be used to predict HIV-1 coreceptor usage.

  8. Longitudinal studies on maternal HIV-1 variants by biological phenotyping, sequence analysis and viral load.

    PubMed

    Renta, J Y; Cadilla, C L; Vega, M E; Hillyer, G V; Estrada, C; Jiménez, E; Abreu, E; Méndez, I; Gandía, J; Meléndez-Guerrero, L M

    1997-11-01

    In this study, the HIV-1 variant viruses from ten pregnant women and their infants were isolated and characterized longitudinally in order to determine the role that viral envelope (gp120-V3 loop) gene variation and viral tropism play in vertical transmission. Biological phenotyping of each HIV variant was accomplished by growth in MT-2, and macrophages from healthy and non-HIV-infected donors. Genetic characterization of the variants was accomplished by DNA sequence analysis. All the women enrolled in this study received ZDV therapy. Virus was cultured from eight out of ten env V3-PCR positive mothers. HIV-1 isolates were all non-syncitium inducing variants. None of the mothers were found to transmit HIV, as determined by DNA PCR and quantitative co-cultures on their infants which were seronegative for HIV-1 through one year after birth. Viral cultures from infant blood samples were negative and infants were all healthy. However, nested env V3-PCR detected proviral DNA in five out of ten infants. In contrast, conventional gag-PCR was negative in the same five infants. Sequences of the five maternal-infant pairs were different, suggesting unique infant HIV-1 variants. The three highest maternal viral load values corresponded to infants that were env V3-PCR positive. These results suggest that HIV-1 particles are transmitted from ZDV-treated mothers to infants. Infant follow up is recommended to determine if HIV-1 has been inhibited by the immune system of the infants.

  9. Diversity of HIV type 1 envelope (V3-V5) sequence in HIV type 1-infected Indian children.

    PubMed

    Prakash, Somi Sankaran; Kalra, Rajesh; Lodha, Rakesh; Kabra, Sushil K; Luthra, Kalpana

    2012-05-01

    Abstract We assessed the viral envelope (V3-V5 region) sequence diversity from 13 HIV-1-infected Indian children from north India. All of the 13 children were found to be infected with subtype C viruses. One of the viral sequences exhibited usage of the CXCR4 coreceptor predicted by Web PSSM and Geno2pheno tools. This virus also had a longer V3 sequence with 37 amino acids, a GRGQ motif, and a methionine residue before it (AIIMS_307). A unique finding was the complete deletion of the V4 region of another virus (AIIMS_363). High sequence diversity was observed in the envelope of the HIV-1-infected Indian children.

  10. In vitro HIV-1 selective integration into the target sequence and decoy-effect of the modified sequence.

    PubMed

    Tsuruyama, Tatsuaki; Nakai, Tonau; Hiratsuka, Takuya; Jin, Guang; Nakamura, Takuro; Yoshikawa, Kenichi

    2010-01-01

    Although there have been a few reports that the HIV-1 genome can be selectively integrated into the genomic DNA of cultured host cell, the biochemistry of integration selectivity has not been fully understood. We modified the in vitro integration reaction protocol and developed a reaction system with higher efficiency. We used a substrate repeat, 5'-(GTCCCTTCCCAGT)(n)(ACTGGGAAGGGAC)(n)-3', and a modified sequence DNA ligated into a circular plasmid. CAGT and ACTG (shown in italics in the above sequence) in the repeat units originated from the HIV-1 proviral genome ends. Following the incubation of the HIV-1 genome end cDNA and recombinant integrase for the formation of the pre-integration (PI) complex, substrate DNA was reacted with this complex. It was confirmed that the integration selectively occurred in the middle segment of the repeat sequence. In addition, integration frequency and selectivity were positively correlated with repeat number n. On the other hand, both frequency and selectivity decreased markedly when using sequences with deletion of CAGT in the middle position of the original target sequence. Moreover, on incubation with the deleted DNAs and original sequence, the integration efficiency and selectivity for the original target sequence were significantly reduced, which indicated interference effects by the deleted sequence DNAs. Efficiency and selectivity were also found to vary discontinuously with changes in manganese dichloride concentration in the reaction buffer, probably due to its influence on the secondary structure of substrate DNA. Finally, integrase was found to form oligomers on the binding site and substrate DNA formed a loop-like structure. In conclusion, there is a considerable selectivity in HIV-integration into the specified sequence; however, similar DNA sequences can interfere with the integration process, and it is therefore difficult for in vivo integration to occur selectively in the actual host genome DNA.

  11. Translating HIV sequences into quantitative fitness landscapes predicts viral vulnerabilities for rational immunogen design.

    PubMed

    Ferguson, Andrew L; Mann, Jaclyn K; Omarjee, Saleha; Ndung'u, Thumbi; Walker, Bruce D; Chakraborty, Arup K

    2013-03-21

    A prophylactic or therapeutic vaccine offers the best hope to curb the HIV-AIDS epidemic gripping sub-Saharan Africa, but it remains elusive. A major challenge is the extreme viral sequence variability among strains. Systematic means to guide immunogen design for highly variable pathogens like HIV are not available. Using computational models, we have developed an approach to translate available viral sequence data into quantitative landscapes of viral fitness as a function of the amino acid sequences of its constituent proteins. Predictions emerging from our computationally defined landscapes for the proteins of HIV-1 clade B Gag were positively tested against new in vitro fitness measurements and were consistent with previously defined in vitro measurements and clinical observations. These landscapes chart the peaks and valleys of viral fitness as protein sequences change and inform the design of immunogens and therapies that can target regions of the virus most vulnerable to selection pressure.

  12. Los Alamos National Laboratory Overview

    SciTech Connect

    Neu, Mary

    2010-06-02

    Mary Neu, Associate Director for Chemistry, Life and Earth Sciences at Los Alamos National Laboratory, delivers opening remarks at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

  13. Sequence quality analysis tool for HIV type 1 protease and reverse transcriptase.

    PubMed

    Delong, Allison K; Wu, Mingham; Bennett, Diane; Parkin, Neil; Wu, Zhijin; Hogan, Joseph W; Kantor, Rami

    2012-08-01

    Access to antiretroviral therapy is increasing globally and drug resistance evolution is anticipated. Currently, protease (PR) and reverse transcriptase (RT) sequence generation is increasing, including the use of in-house sequencing assays, and quality assessment prior to sequence analysis is essential. We created a computational HIV PR/RT Sequence Quality Analysis Tool (SQUAT) that runs in the R statistical environment. Sequence quality thresholds are calculated from a large dataset (46,802 PR and 44,432 RT sequences) from the published literature ( http://hivdb.Stanford.edu ). Nucleic acid sequences are read into SQUAT, identified, aligned, and translated. Nucleic acid sequences are flagged if with >five 1-2-base insertions; >one 3-base insertion; >one deletion; >six PR or >18 RT ambiguous bases; >three consecutive PR or >four RT nucleic acid mutations; >zero stop codons; >three PR or >six RT ambiguous amino acids; >three consecutive PR or >four RT amino acid mutations; >zero unique amino acids; or <0.5% or >15% genetic distance from another submitted sequence. Thresholds are user modifiable. SQUAT output includes a summary report with detailed comments for troubleshooting of flagged sequences, histograms of pairwise genetic distances, neighbor joining phylogenetic trees, and aligned nucleic and amino acid sequences. SQUAT is a stand-alone, free, web-independent tool to ensure use of high-quality HIV PR/RT sequences in interpretation and reporting of drug resistance, while increasing awareness and expertise and facilitating troubleshooting of potentially problematic sequences.

  14. Reconstructing the Dynamics of HIV Evolution within Hosts from Serial Deep Sequence Data

    PubMed Central

    Poon, Art F. Y.; Swenson, Luke C.; Bunnik, Evelien M.; Edo-Matas, Diana; Schuitemaker, Hanneke; van 't Wout, Angélique B.; Harrigan, P. Richard

    2012-01-01

    At the early stage of infection, human immunodeficiency virus (HIV)-1 predominantly uses the CCR5 coreceptor for host cell entry. The subsequent emergence of HIV variants that use the CXCR4 coreceptor in roughly half of all infections is associated with an accelerated decline of CD4+ T-cells and rate of progression to AIDS. The presence of a ‘fitness valley’ separating CCR5- and CXCR4-using genotypes is postulated to be a biological determinant of whether the HIV coreceptor switch occurs. Using phylogenetic methods to reconstruct the evolutionary dynamics of HIV within hosts enables us to discriminate between competing models of this process. We have developed a phylogenetic pipeline for the molecular clock analysis, ancestral reconstruction, and visualization of deep sequence data. These data were generated by next-generation sequencing of HIV RNA extracted from longitudinal serum samples (median 7 time points) from 8 untreated subjects with chronic HIV infections (Amsterdam Cohort Studies on HIV-1 infection and AIDS). We used the known dates of sampling to directly estimate rates of evolution and to map ancestral mutations to a reconstructed timeline in units of days. HIV coreceptor usage was predicted from reconstructed ancestral sequences using the geno2pheno algorithm. We determined that the first mutations contributing to CXCR4 use emerged about 16 (per subject range 4 to 30) months before the earliest predicted CXCR4-using ancestor, which preceded the first positive cell-based assay of CXCR4 usage by 10 (range 5 to 25) months. CXCR4 usage arose in multiple lineages within 5 of 8 subjects, and ancestral lineages following alternate mutational pathways before going extinct were common. We observed highly patient-specific distributions and time-scales of mutation accumulation, implying that the role of a fitness valley is contingent on the genotype of the transmitted variant. PMID:23133358

  15. Reconstructing the dynamics of HIV evolution within hosts from serial deep sequence data.

    PubMed

    Poon, Art F Y; Swenson, Luke C; Bunnik, Evelien M; Edo-Matas, Diana; Schuitemaker, Hanneke; van 't Wout, Angélique B; Harrigan, P Richard

    2012-01-01

    At the early stage of infection, human immunodeficiency virus (HIV)-1 predominantly uses the CCR5 coreceptor for host cell entry. The subsequent emergence of HIV variants that use the CXCR4 coreceptor in roughly half of all infections is associated with an accelerated decline of CD4+ T-cells and rate of progression to AIDS. The presence of a 'fitness valley' separating CCR5- and CXCR4-using genotypes is postulated to be a biological determinant of whether the HIV coreceptor switch occurs. Using phylogenetic methods to reconstruct the evolutionary dynamics of HIV within hosts enables us to discriminate between competing models of this process. We have developed a phylogenetic pipeline for the molecular clock analysis, ancestral reconstruction, and visualization of deep sequence data. These data were generated by next-generation sequencing of HIV RNA extracted from longitudinal serum samples (median 7 time points) from 8 untreated subjects with chronic HIV infections (Amsterdam Cohort Studies on HIV-1 infection and AIDS). We used the known dates of sampling to directly estimate rates of evolution and to map ancestral mutations to a reconstructed timeline in units of days. HIV coreceptor usage was predicted from reconstructed ancestral sequences using the geno2pheno algorithm. We determined that the first mutations contributing to CXCR4 use emerged about 16 (per subject range 4 to 30) months before the earliest predicted CXCR4-using ancestor, which preceded the first positive cell-based assay of CXCR4 usage by 10 (range 5 to 25) months. CXCR4 usage arose in multiple lineages within 5 of 8 subjects, and ancestral lineages following alternate mutational pathways before going extinct were common. We observed highly patient-specific distributions and time-scales of mutation accumulation, implying that the role of a fitness valley is contingent on the genotype of the transmitted variant.

  16. Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes

    NASA Astrophysics Data System (ADS)

    Shekhar, Karthik; Ruberman, Claire F.; Ferguson, Andrew L.; Barton, John P.; Kardar, Mehran; Chakraborty, Arup K.

    2013-12-01

    Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.

  17. Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs

    PubMed Central

    Schopman, Nick C.T.; Willemsen, Marcel; Liu, Ying Poi; Bradley, Ted; van Kampen, Antoine; Baas, Frank; Berkhout, Ben; Haasnoot, Joost

    2012-01-01

    Small virus-derived interfering RNAs (viRNAs) play an important role in antiviral defence in plants, insects and nematodes by triggering the RNA interference (RNAi) pathway. The role of RNAi as an antiviral defence mechanism in mammalian cells has been obscure due to the lack of viRNA detection. Although viRNAs from different mammalian viruses have recently been identified, their functions and possible impact on viral replication remain unknown. To identify viRNAs derived from HIV-1, we used the extremely sensitive SOLiDTM 3 Plus System to analyse viRNA accumulation in HIV-1-infected T lymphocytes. We detected numerous small RNAs that correspond to the HIV-1 RNA genome. The majority of these sequences have a positive polarity (98.1%) and could be derived from miRNAs encoded by structured segments of the HIV-1 RNA genome (vmiRNAs). A small portion of the viRNAs is of negative polarity and most of them are encoded within the 3′-UTR, which may represent viral siRNAs (vsiRNAs). The identified vsiRNAs can potently repress HIV-1 production, whereas suppression of the vsiRNAs by antagomirs stimulate virus production. These results suggest that HIV-1 triggers the production of vsiRNAs and vmiRNAs to modulate cellular and/or viral gene expression. PMID:21911362

  18. Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs.

    PubMed

    Schopman, Nick C T; Willemsen, Marcel; Liu, Ying Poi; Bradley, Ted; van Kampen, Antoine; Baas, Frank; Berkhout, Ben; Haasnoot, Joost

    2012-01-01

    Small virus-derived interfering RNAs (viRNAs) play an important role in antiviral defence in plants, insects and nematodes by triggering the RNA interference (RNAi) pathway. The role of RNAi as an antiviral defence mechanism in mammalian cells has been obscure due to the lack of viRNA detection. Although viRNAs from different mammalian viruses have recently been identified, their functions and possible impact on viral replication remain unknown. To identify viRNAs derived from HIV-1, we used the extremely sensitive SOLiD(TM) 3 Plus System to analyse viRNA accumulation in HIV-1-infected T lymphocytes. We detected numerous small RNAs that correspond to the HIV-1 RNA genome. The majority of these sequences have a positive polarity (98.1%) and could be derived from miRNAs encoded by structured segments of the HIV-1 RNA genome (vmiRNAs). A small portion of the viRNAs is of negative polarity and most of them are encoded within the 3'-UTR, which may represent viral siRNAs (vsiRNAs). The identified vsiRNAs can potently repress HIV-1 production, whereas suppression of the vsiRNAs by antagomirs stimulate virus production. These results suggest that HIV-1 triggers the production of vsiRNAs and vmiRNAs to modulate cellular and/or viral gene expression. PMID:21911362

  19. CD4+ T Cell Targeting of Human Immunodeficiency Virus Type 1 (HIV-1) Peptide Sequences Present In Vivo during Chronic, Progressive HIV-1 Disease

    PubMed Central

    Boritz, Eli; Rapaport, Eric L.; Campbell, Thomas B.; Koeppe, John R.; Wilson, Cara C.

    2009-01-01

    We previously detected HIV-1 Gag-specific CD4+ T cells recognizing reference strain viral epitopes in subjects with progressive, chronic infection. To test whether these CD4+ T cells persist in vivo by failing to recognize autologous HIV-1 epitopes, we compared autologous plasma HIV-1 p24 nucleotide sequences with targeted HXB.2 strain Gag p24 CD4+ T cell epitopes in nine chronically-infected, untreated subjects. In five responding subjects, 10 of 26 HXB.2 strain p24 peptides targeted by CD4+ T cells exactly matched autologous plasma viral sequences. Four subjects with plasma viral loads >100,000 copies/mL had no measurable p24-specific CD4+ T cell responses despite carrying HIV-1 strains that matched HXB.2 sequences at predicted epitopes. These results show that HIV-1-specific CD4+ T cells can persist in chronic HIV-1 infection despite recognition of epitopes present in vivo. However, with high level in vivo HIV-1 replication, CD4+ T cells targeting autologous HIV-1 may be non-responsive or absent. PMID:17169395

  20. Deep Sequencing of HIV-Infected Cells: Insights into Nascent Transcription and Host-Directed Therapy

    PubMed Central

    Peng, Xinxia; Sova, Pavel; Green, Richard R.; Thomas, Matthew J.; Korth, Marcus J.; Proll, Sean; Xu, Jiabao; Cheng, Yanbing; Yi, Kang; Chen, Li; Peng, Zhiyu; Wang, Jun; Palermo, Robert E.

    2014-01-01

    ABSTRACT Polyadenylated mature mRNAs are the focus of standard transcriptome analyses. However, the profiling of nascent transcripts, which often include nonpolyadenylated RNAs, can unveil novel insights into transcriptional regulation. Here, we separately sequenced total RNAs (Total RNAseq) and mRNAs (mRNAseq) from the same HIV-1-infected human CD4+ T cells. We found that many nonpolyadenylated RNAs were differentially expressed upon HIV-1 infection, and we identified 8 times more differentially expressed genes at 12 h postinfection by Total RNAseq than by mRNAseq. These expression changes were also evident by concurrent changes in introns and were recapitulated by later mRNA changes, revealing an unexpectedly significant delay between transcriptional initiation and mature mRNA production early after HIV-1 infection. We computationally derived and validated the underlying regulatory programs, and we predicted drugs capable of reversing these HIV-1-induced expression changes followed by experimental confirmation. Our results show that combined total and mRNA transcriptome analysis is essential for fully capturing the early host response to virus infection and provide a framework for identifying candidate drugs for host-directed therapy against HIV/AIDS. IMPORTANCE In this study, we used mass sequencing to identify genes differentially expressed in CD4+ T cells during HIV-1 infection. To our surprise, we found many differentially expressed genes early after infection by analyzing both newly transcribed unprocessed pre-mRNAs and fully processed mRNAs, but not by analyzing mRNAs alone, indicating a significant delay between transcription initiation and mRNA production early after HIV-1 infection. These results also show that important findings could be missed by the standard practice of analyzing mRNAs alone. We then derived the regulatory mechanisms driving the observed expression changes using integrative computational analyses. Further, we predicted drugs that

  1. Genome-Wide Association Study of HIV Whole Genome Sequences Validated using Drug Resistance

    PubMed Central

    Power, Robert A.; Davaniah, Siva; Derache, Anne; Wilkinson, Eduan; Tanser, Frank; Pillay, Deenan; de Oliveira, Tulio

    2016-01-01

    Background Genome-wide association studies (GWAS) have considerably advanced our understanding of human traits and diseases. With the increasing availability of whole genome sequences (WGS) for pathogens, it is important to establish whether GWAS of viral genomes could reveal important biological insights. Here we perform the first proof of concept viral GWAS examining drug resistance (DR), a phenotype with well understood genetics. Method We performed a GWAS of DR in a sample of 343 HIV subtype C patients failing 1st line antiretroviral treatment in rural KwaZulu-Natal, South Africa. The majority and minority variants within each sequence were called using PILON, and GWAS was performed within PLINK. HIV WGS from patients failing on different antiretroviral treatments were compared to sequences derived from individuals naïve to the respective treatment. Results GWAS methodology was validated by identifying five associations on a genetic level that led to amino acid changes known to cause DR. Further, we highlighted the ability of GWAS to identify epistatic effects, identifying two replicable variants within amino acid 68 of the reverse transcriptase protein previously described as potential fitness compensatory mutations. A possible additional DR variant within amino acid 91 of the matrix region of the Gag protein was associated with tenofovir failure, highlighting GWAS’s ability to identify variants outside classical candidate genes. Our results also suggest a polygenic component to DR. Conclusions These results validate the applicability of GWAS to HIV WGS data even in relative small samples, and emphasise how high throughput sequencing can provide novel and clinically relevant insights. Further they suggested that for viruses like HIV, population structure was only minor concern compared to that seen in bacteria or parasite GWAS. Given the small genome length and reduced burden for multiple testing, this makes HIV an ideal candidate for GWAS. PMID:27677172

  2. Evaluation of GS Junior and MiSeq next-generation sequencing technologies as an alternative to Trugene population sequencing in the clinical HIV laboratory.

    PubMed

    Ram, Daniela; Leshkowitz, Dena; Gonzalez, Dimitri; Forer, Relly; Levy, Itzchak; Chowers, Michal; Lorber, Margalit; Hindiyeh, Musa; Mendelson, Ella; Mor, Orna

    2015-02-01

    Population HIV-1 sequencing is currently the method of choice for the identification and follow-up of HIV-1 antiretroviral drug resistance. It has limited sensitivity and results in a consensus sequence showing the most prevalent nucleotide per position. Moreover concomitant sequencing and interpretation of the results for several samples together is laborious and time consuming. In this study, the practical use of GS Junior and MiSeq bench-top next generation sequencing (NGS) platforms as an alternative to Trugene Sanger-based population sequencing in the clinical HIV laboratory was assessed. DeepChek(®)-HIV TherapyEdge software was used for processing all the protease and reverse transcriptase sequences and for resistance interpretation. Plasma samples from nine HIV-1 carriers, representing the major HIV-1 subtypes in Israel, were compared. The total number of amino acid substitutions identified in the nine samples by GS Junior (232 substitutions) and MiSeq (243 substitutions) was similar and higher than Trugene (181 substitutions), emphasizing the advantage of deep sequencing on population sequencing. More than 80% of the identified substitutions were identical between the GS Junior and MiSeq platforms, most of which (184 of 199) at similar frequency. Low abundance substitutions accounted for 20.9% of the MiSeq and 21.9% of the GS Junior output, the majority of which were not detected by Trugene. More drug resistance mutations were identified by both the NGS platforms, primarily, but not only, at low abundance. In conclusion, in combination with DeepChek, both GS Junior and MiSeq were found to be more sensitive than Trugene and adequate for HIV-1 resistance analysis in the clinical HIV laboratory.

  3. Evaluation of GS Junior and MiSeq next-generation sequencing technologies as an alternative to Trugene population sequencing in the clinical HIV laboratory.

    PubMed

    Ram, Daniela; Leshkowitz, Dena; Gonzalez, Dimitri; Forer, Relly; Levy, Itzchak; Chowers, Michal; Lorber, Margalit; Hindiyeh, Musa; Mendelson, Ella; Mor, Orna

    2015-02-01

    Population HIV-1 sequencing is currently the method of choice for the identification and follow-up of HIV-1 antiretroviral drug resistance. It has limited sensitivity and results in a consensus sequence showing the most prevalent nucleotide per position. Moreover concomitant sequencing and interpretation of the results for several samples together is laborious and time consuming. In this study, the practical use of GS Junior and MiSeq bench-top next generation sequencing (NGS) platforms as an alternative to Trugene Sanger-based population sequencing in the clinical HIV laboratory was assessed. DeepChek(®)-HIV TherapyEdge software was used for processing all the protease and reverse transcriptase sequences and for resistance interpretation. Plasma samples from nine HIV-1 carriers, representing the major HIV-1 subtypes in Israel, were compared. The total number of amino acid substitutions identified in the nine samples by GS Junior (232 substitutions) and MiSeq (243 substitutions) was similar and higher than Trugene (181 substitutions), emphasizing the advantage of deep sequencing on population sequencing. More than 80% of the identified substitutions were identical between the GS Junior and MiSeq platforms, most of which (184 of 199) at similar frequency. Low abundance substitutions accounted for 20.9% of the MiSeq and 21.9% of the GS Junior output, the majority of which were not detected by Trugene. More drug resistance mutations were identified by both the NGS platforms, primarily, but not only, at low abundance. In conclusion, in combination with DeepChek, both GS Junior and MiSeq were found to be more sensitive than Trugene and adequate for HIV-1 resistance analysis in the clinical HIV laboratory. PMID:25445792

  4. HIV-1 sequence variation between isolates from mother-infant transmission pairs

    SciTech Connect

    Wike, C.M.; Daniels, M.R.; Furtado, M.; Wolinsky, M.; Korber, B.; Hutto, C.; Munoz, J.; Parks, W.; Saah, A.

    1991-01-01

    To examine the sequence diversity of human immunodeficiency virus type 1 (HIV-1) between known transmission sets, sequences from the V3 and V4-V5 region of the env gene from 4 mother-infant pairs were analyzed. The mean interpatient sequence variation between isolates from linked mother-infant pairs was comparable to the sequence diversity found between isolates from other close contacts. The mean intrapatient variation was significantly less in the infants' isolates then the isolates from both their mothers and other characterized intrapatient sequence sets. In addition, a distinct and characteristic difference in the glycosylation pattern preceding the V3 loop was found between each linked transmission pair. These findings indicate that selection of specific genotypic variants, which may play a role in some direct transmission sets, and the duration of infection are important factors in the degree of diversity seen between the sequence sets.

  5. HIV-1 sequence variation between isolates from mother-infant transmission pairs

    SciTech Connect

    Wike, C.M.; Daniels, M.R.; Furtado, M.; Wolinsky, M.; Korber, B.; Hutto, C.; Munoz, J.; Parks, W.; Saah, A.

    1991-12-31

    To examine the sequence diversity of human immunodeficiency virus type 1 (HIV-1) between known transmission sets, sequences from the V3 and V4-V5 region of the env gene from 4 mother-infant pairs were analyzed. The mean interpatient sequence variation between isolates from linked mother-infant pairs was comparable to the sequence diversity found between isolates from other close contacts. The mean intrapatient variation was significantly less in the infants` isolates then the isolates from both their mothers and other characterized intrapatient sequence sets. In addition, a distinct and characteristic difference in the glycosylation pattern preceding the V3 loop was found between each linked transmission pair. These findings indicate that selection of specific genotypic variants, which may play a role in some direct transmission sets, and the duration of infection are important factors in the degree of diversity seen between the sequence sets.

  6. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing

    SciTech Connect

    Wu, Xueling; Zhou, Tongqing; Zhu, Jiang; Zhang, Baoshan; Georgiev, Ivelin; Wang, Charlene; Chen, Xuejun; Longo, Nancy S.; Louder, Mark; McKee, Krisha; O’Dell, Sijy; Perfetto, Stephen; Schmidt, Stephen D.; Shi, Wei; Wu, Lan; Yang, Yongping; Yang, Zhi-Yong; Yang, Zhongjia; Zhang, Zhenhai; Bonsignori, Mattia; Crump, John A.; Kapiga, Saidi H.; Sam, Noel E.; Haynes, Barton F.; Simek, Melissa; Burton, Dennis R.; Koff, Wayne C.; Doria-Rose, Nicole A.; Connors, Mark; Mullikin, James C.; Nabel, Gary J.; Roederer, Mario; Shapiro, Lawrence; Kwong, Peter D.; Mascola, John R.

    2013-03-04

    Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution of antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.

  7. Utility of Metagenomic Next-Generation Sequencing for Characterization of HIV and Human Pegivirus Diversity

    PubMed Central

    Naccache, Samia N.; Kabre, Beniwende; Federman, Scot; Mbanya, Dora; Kaptué, Lazare; Chiu, Charles Y.; Brennan, Catherine A.; Hackett, John

    2015-01-01

    Given the dynamic changes in HIV-1 complexity and diversity, next-generation sequencing (NGS) has the potential to revolutionize strategies for effective HIV global surveillance. In this study, we explore the utility of metagenomic NGS to characterize divergent strains of HIV-1 and to simultaneously screen for other co-infecting viruses. Thirty-five HIV-1-infected Cameroonian blood donor specimens with viral loads of >4.4 log10 copies/ml were selected to include a diverse representation of group M strains. Random-primed NGS libraries, prepared from plasma specimens, resulted in greater than 90% genome coverage for 88% of specimens. Correct subtype designations based on NGS were concordant with sub-region PCR data in 31 of 35 (89%) cases. Complete genomes were assembled for 25 strains, including circulating recombinant forms with relatively limited data available (7 CRF11_cpx, 2 CRF13_cpx, 1 CRF18_cpx, and 1 CRF37_cpx), as well as 9 unique recombinant forms. HPgV (formerly designated GBV-C) co-infection was detected in 9 of 35 (25%) specimens, of which eight specimens yielded complete genomes. The recovered HPgV genomes formed a diverse cluster with genotype 1 sequences previously reported from Ghana, Uganda, and Japan. The extensive genome coverage obtained by NGS improved accuracy and confidence in phylogenetic classification of the HIV-1 strains present in the study population relative to conventional sub-region PCR. In addition, these data demonstrate the potential for metagenomic analysis to be used for routine characterization of HIV-1 and identification of other viral co-infections. PMID:26599538

  8. HIV-1 intrapatient sequence diversity in the immunogenic V3 region

    SciTech Connect

    Korber, B.; Myers, G.; Wolinsky, S.; Kunstman, K.; Levy, R.; Furtado, M.; Otto, P.; Haynes, B.

    1991-11-12

    The third hypervariable domain (V3) of the human immunodeficiency virus type-1 (HIV-1) envelope protein (env) can serve as an epitope for potent type-specific neutralizing antibodies (NAbs) -- thus short peptides predicted on the most commonly found variants of the antigenic tip of the V3 loop have been considered as potential candidates for an HIV peptide vaccine. To evaluate the extent of intrapatient variation in the immunogenic crest of the V3 loop, sequence sets were analyzed from individuals for whom multiple V3 sequences were available. Several strategies for selecting the best sets of hexapeptides to represent the variable tip of the V3 loop were considered and their effectiveness was evaluated by comparing them with the sequence sets from individuals. Most individuals carried at least one, and frequently many, variants that did not match any of the sequences from among the ten most common hexapeptides. Intrapatient viral sequence variation was increased by including sequences derived from brain biopsy specimens as well as from blood. Additionally, sequences obtained from brain specimens of different individuals had common elements which were not conserved in the corresponding blood samples, suggesting that certain amino acids in the V3 loop may be requisite for viral propagation in the CNS.

  9. Sequence and structure requirements for specific recognition of HIV-1 TAR and DIS RNA by the HIV-1 Vif protein.

    PubMed

    Freisz, Séverine; Mezher, Joelle; Hafirassou, Lamine; Wolff, Philippe; Nominé, Yves; Romier, Christophe; Dumas, Philippe; Ennifar, Eric

    2012-07-01

    The HIV-1 Vif protein plays an essential role in the regulation of the infectivity of HIV-1 virion and in vivo pathogenesis. Vif neutralizes the human DNA-editing enzyme APOBEC3 protein, an antiretroviral cellular factor from the innate immune system, allowing the virus to escape the host defence system. It was shown that Vif is packaged into viral particles through specific interactions with the viral genomic RNA. Conserved and structured sequences from the 5'-noncoding region, such as the Tat-responsive element (TAR) or the genomic RNA dimerization initiation site (DIS), are primary binding sites for Vif. In the present study we used isothermal titration calorimetry to investigate sequence and structure determinants important for Vif binding to short viral RNA corresponding to TAR and DIS stem-loops. We showed that Vif specifically binds TAR and DIS in the low nanomolar range. In addition, Vif primarily binds the TAR UCU bulge, but not the apical loop. Determinants for Vif binding to the DIS loop-loop complex are likely more complex and involve the self-complementary loop together with the upper part of the stem. These results suggest that Tat-TAR inhibitors or DIS small molecule binders might be also effective to disturb Vif-TAR and Vif-DIS binding in order to reduce Vif packaging into virions.

  10. Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development

    DOE PAGES

    Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Korber, Bette T.; Barouch, Dan H.

    2014-11-14

    An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth ofmore » IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.« less

  11. Quantification of the epitope diversity of HIV-1-specific binding antibodies by peptide microarrays for global HIV-1 vaccine development

    SciTech Connect

    Stephenson, Kathryn E.; Neubauer, George H.; Reimer, Ulf; Pawlowski, Nikolaus; Knaute, Tobias; Zerweck, Johannes; Korber, Bette T.; Barouch, Dan H.

    2014-11-14

    An effective vaccine against human immunodeficiency virus type 1 (HIV-1) will have to provide protection against a vast array of different HIV-1 strains. Current methods to measure HIV-1-specific binding antibodies following immunization typically focus on determining the magnitude of antibody responses, but the epitope diversity of antibody responses has remained largely unexplored. Here we describe the development of a global HIV-1 peptide microarray that contains 6564 peptides from across the HIV-1 proteome and covers the majority of HIV-1 sequences in the Los Alamos National Laboratory global HIV-1 sequence database. Using this microarray, we quantified the magnitude, breadth, and depth of IgG binding to linear HIV-1 sequences in HIV-1-infected humans and HIV-1-vaccinated humans, rhesus monkeys and guinea pigs. The microarray measured potentially important differences in antibody epitope diversity, particularly regarding the depth of epitope variants recognized at each binding site. Our data suggest that the global HIV-1 peptide microarray may be a useful tool for both preclinical and clinical HIV-1 research.

  12. Sequence-specific interaction between HIV-1 matrix protein and viral genomic RNA revealed by in vitro genetic selection.

    PubMed Central

    Purohit, P; Dupont, S; Stevenson, M; Green, M R

    2001-01-01

    The human immunodeficiency virus type-1 matrix protein (HIV-1 MA) is a multifunctional structural protein synthesized as part of the Pr55 gag polyprotein. We have used in vitro genetic selection to identify an RNA consensus sequence that specifically interacts with MA (Kd = 5 x 10(-7) M). This 13-nt MA binding consensus sequence bears a high degree of homology (77%) to a region (nt 1433-1446) within the POL open reading frame of the HIV-1 genome (consensus sequence from 38 HIV-1 strains). Chemical interference experiments identified the nucleotides within the MA binding consensus sequence involved in direct contact with MA. We further demonstrate that this RNA-protein interaction is mediated through a stretch of basic amino acids within MA. Mutations that disrupt the interaction between MA and its RNA binding site within the HIV-1 genome resulted in a measurable decrease in viral replication. PMID:11345436

  13. Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland.

    PubMed

    Shilaih, Mohaned; Marzel, Alex; Yang, Wan Lin; Scherrer, Alexandra U; Schüpbach, Jörg; Böni, Jürg; Yerly, Sabine; Hirsch, Hans H; Aubert, Vincent; Cavassini, Matthias; Klimkait, Thomas; Vernazza, Pietro L; Bernasconi, Enos; Furrer, Hansjakob; Günthard, Huldrych F; Kouyos, Roger

    2016-01-01

    Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8-2.1), female gender (OR: 1.6; 95% CI: 1.4-1.7), black ethnicity (OR: 1.9; 95% CI: 1.7-2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6-2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS'. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance. PMID:27297284

  14. Genotypic Resistance Tests Sequences Reveal the Role of Marginalized Populations in HIV-1 Transmission in Switzerland

    PubMed Central

    Shilaih, Mohaned; Marzel, Alex; Yang, Wan Lin; Scherrer, Alexandra U.; Schüpbach, Jörg; Böni, Jürg; Yerly, Sabine; Hirsch, Hans H.; Aubert, Vincent; Cavassini, Matthias; Klimkait, Thomas; Vernazza, Pietro L.; Bernasconi, Enos; Furrer, Hansjakob; Günthard, Huldrych F.; Kouyos, Roger; Battegay, Manuel; Braun, Dominique; Bucher, Heiner; Burton-Jeangros, Claudine; Calmy, Alexandra; Dollenmaier, Günter; Egger, Matthias; Elzi, Luigia; Fehr, Jan; Fellay, Jaque; Fux, Christoph; Gorgievski, Meri; Haerry, David; Hasse, Barbara; Hoffmann, Matthias; Hösli, Irene; Kahlert, Christian; Kaiser, Laurent; Keiser, Olivia; Kovari, Helen; Ledergerber, Bruno; Martinetti, Gladys; de Tejada, Begoña Martinez; Marzolini, Catia; Metzner, Karin; Müller, Nicolas; Nadal, David; Nicca, Dunja; Pantaleo, Giuseppe; Rauch, Andre; Regenass, Stephan; Rudin, Christoph; Schöni-Affolter, Franziska; Schmid, Patrick; Speck, Roberto; Stöckle, Marcel; Tarr, Philip; Trkola, Alexandra; Weber, Reiner

    2016-01-01

    Targeting hard-to-reach/marginalized populations is essential for preventing HIV-transmission. A unique opportunity to identify such populations in Switzerland is provided by a database of all genotypic-resistance-tests from Switzerland, including both sequences from the Swiss HIV Cohort Study (SHCS) and non-cohort sequences. A phylogenetic tree was built using 11,127 SHCS and 2,875 Swiss non-SHCS sequences. Demographics were imputed for non-SHCS patients using a phylogenetic proximity approach. Factors associated with non-cohort outbreaks were determined using logistic regression. Non-B subtype (univariable odds-ratio (OR): 1.9; 95% confidence interval (CI): 1.8–2.1), female gender (OR: 1.6; 95% CI: 1.4–1.7), black ethnicity (OR: 1.9; 95% CI: 1.7–2.1) and heterosexual transmission group (OR:1.8; 95% CI: 1.6–2.0), were all associated with underrepresentation in the SHCS. We found 344 purely non-SHCS transmission clusters, however, these outbreaks were small (median 2, maximum 7 patients) with a strong overlap with the SHCS’. 65% of non-SHCS sequences were part of clusters composed of >= 50% SHCS sequences. Our data suggests that marginalized-populations are underrepresented in the SHCS. However, the limited size of outbreaks among non-SHCS patients in-care implies that no major HIV outbreak in Switzerland was missed by the SHCS surveillance. This study demonstrates the potential of sequence data to assess and extend the scope of infectious-disease surveillance. PMID:27297284

  15. Diversity of full-length subtype E HIV type 1 env sequences in early seroconvertors from northern Thailand.

    PubMed

    Yu, X F; Wang, Z; Beyrer, C; Celentano, D D; Khamboonruang, C; Nelson, K

    1997-11-01

    Although both HIV-1 subtypes B and E have been identified from infected individuals in Thailand, subtype E is the main form of HIV currently circulating in the country. Full-length gp160 sequences were obtained from 2 early seroconverters from northern Thailand in a study to learn more about the HIV-1 sequences currently being transmitted among recently infected individuals. Subject A01021 was a female prostitute who tested negative for antibodies to HIV-1 in April 1993, then positive in July 1993. Subject E11429 was a male military conscript who tested negative for antibodies to HIV-1 in May 1993, then positive in November 1993. Uncultured peripheral blood mononuclear cells (PBMCs) were collected from these two individuals in January 1994 and about 2500-bp segments containing the full-length gp160 gene were amplified by nested polymerase chain reaction (PCR) using the Expand high-fidelity PCR system. The nucleotide sequences of full-length gp120 from the subjects were subtype E based upon phylogenetic analysis. The gp120 sequences from the 2 seroconverters appeared more diverse than previously published subtype E HIV-1 sequences from Thailand. Overall, however, the subtype E HIV-1 gp120 sequences from Thailand were less diversified compared to the subtype E HIV-1 isolated from people with AIDS in the Central African Republic. Most of the observed amino acid variations were limited to the 5 variable regions in gp120. Therefore, vaccine strategies which elicit immune responses to the conserved regions of HIV-1 env protein will have a greater possibility of success.

  16. Identification of HIV Mutation as Diagnostic Biomarker through Next Generation Sequencing

    PubMed Central

    Shaw, Wen Hui; Lin, Qianqian; Muhammad, Zikry Zhiwei Bin Roslee; Lee, Jia Jun; Khong, Wei Xin; Ng, Oon Tek; Tan, Eng Lee

    2016-01-01

    Introduction Current clinical detection of Human immunodeficiency virus 1 (HIV-1) is used to target viral genes and proteins. However, the immunoassay, such as viral culture or Polymerase Chain Reaction (PCR), lacks accuracy in the diagnosis, as these conventional assays rely on the stable genome and HIV-1 is a highly-mutated virus. Next generation sequencing (NGS) promises to be transformative for the practice of infectious disease, and the rapidly reducing cost and processing time mean that this will become a feasible technology in diagnostic and research laboratories in the near future. The technology offers the superior sensitivity to detect the pathogenic viruses, including unknown and unexpected strains. Aim To leverage the NGS technology in order to improve current HIV-1 diagnosis and genotyping methods. Materials and Methods Ten blood samples were collected from HIV-1 infected patients which were diagnosed by RT PCR at Singapore Communicable Disease Centre, Tan Tock Seng Hospital from October 2014 to March 2015. Viral RNAs were extracted from blood plasma and reversed into cDNA. The HIV-1 cDNA samples were cleaned up using a PCR purification kit and the sequencing library was prepared and identified through MiSeq. Results Two common mutations were observed in all ten samples. The common mutations were identified at genome locations 1908 and 2104 as missense and silent mutations respectively, conferring S37N and S3S found on aspartic protease and reverse transcriptase subunits. Conclusion The common mutations identified in this study were not previously reported, therefore suggesting the potential for them to be used for identification of viral infection, disease transmission and drug resistance. This was especially the case for, missense mutation S37N which could cause an amino acid change in viral proteases thus reducing the binding affinity of some protease inhibitors. Thus, the unique common mutations identified in this study could be used as diagnostic

  17. Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes.

    PubMed

    Shekhar, Karthik; Ruberman, Claire F; Ferguson, Andrew L; Barton, John P; Kardar, Mehran; Chakraborty, Arup K

    2013-12-01

    Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses. PMID:24483484

  18. Structural Conservation Predominates Over Sequence Variability in the Crown of HIV Type 1's V3 Loop

    PubMed Central

    Almond, David; Kimura, Tetsuya; Kong, XiangPeng; Swetnam, James; Zolla-Pazner, Susan

    2010-01-01

    Abstract The diversity of HIV-1 is a confounding problem for vaccine design, as the human immune response appears to favor poor or strain-specific responses to any given HIV-1 virus strain. A significant portion of this diversity is manifested as sequence variability in the loops of HIV-1's surface envelope glycoprotein. Here we show that the most variable sequence positions in the third variable (V3) loop crown cluster to a small zone on the surface of one face of the V3 loop ß-hairpin conformation. These results provide a novel visualization of the gp120 V3 loop, specifically demonstrating a surprising preponderance of conserved three-dimensional structure in a highly sequence-variable region. From a structural point of view, there appears to be less diversity in this region of the HIV-1 “principle neutralizing domain” than previously appreciated. PMID:20560796

  19. Nautilus: a bioinformatics package for the analysis of HIV type 1 targeted deep sequencing data.

    PubMed

    Kijak, Gustavo H; Pham, Phuc; Sanders-Buell, Eric; Harbolick, Elizabeth A; Eller, Leigh Anne; Robb, Merlin L; Michael, Nelson L; Kim, Jerome H; Tovanabutra, Sodsai

    2013-10-01

    The advent of next generation sequencing technologies is providing new insight into HIV-1 diversity and evolution, which has created the need for bioinformatics tools that could be applied to the characterization of viral quasispecies. Here we present Nautilus, a bioinformatics package for the analysis of HIV-1 targeted deep sequencing data. The DeepHaplo module determines the nucleotide base frequency and read depth at each position and computes the haplotype frequencies based on the linkage among polymorphisms in the same next generation sequence read. The Motifs module computes the frequency of the variants in the setting of their sequence context and mapping orientation, which allows for the validation of polymorphisms and haplotypes when strand bias is suspected. Both modules are accessed through a user-friendly GUI, which runs on Mac OS X (version 10.7.4 or later), and are based on Python, JAVA, and R scripts. Nautilus is available from www.hivresearch.org/research.php?ServiceID=5&SubServiceID=6 . PMID:23809062

  20. STD/HIV prevention in Turkey: planning a sequence of interventions.

    PubMed

    Aral, S O; Fransen, L

    1995-12-01

    This study was initiated to assess which mix of early STD/HIV prevention interventions would potentially be effective, cost-effective and sustainable in Turkey; and to program an intervention sequence to maximize synergy among the interventions. During rapid assessment we: 1) reviewed past issues of 3 leading newspapers; 2) collected information on TV coverage; 3) interviewed key informants including taxicab drivers, hotel employees, grocery store owners, academicians in public health and law, investigators of STD/HIV and reproductive tract infections, and officials in the ministry of health; 4) reviewed available evidence on STD/HIV morbidity, sexual behavior patterns, migration patterns and same/opposite gender sex trade. We found: 1) discrepancies between decision makers' perceptions and social realities with respect to the epidemiology of sexual behavior and STDs, and the state of public health programs; 2) discrepancies between sexual practices and public expression regarding sexual practices; 3) economic, demographic, and political pressures in Turkey and in surrounding countries for the expansion of prostitution; 4) a sexual double standard and gender specific migration patterns which sustain a high demand for commercial sex; 5) patterns of health care seeking behaviors and provision of STD clinical services which indicate other STDs may play a very important role in spread of HIV infection; 6) an important mass media role in opinion formation; 7) consensual denial of risk for the majority based on beliefs embedded in machismo, nationalism and religion, and a resulting marginalization and externalization of STD/HIV risk; 8) high prevalence of syphilis among both Turkish and immigrant female prostitutes in Istanbul (early latent 8 and 13%; late latent 0 and 4%; previous history 9 and 22%) 9) and high rates of syphilis among male prostitutes (early latent 11%, late latent 21% and previous history 58%). We concluded that interventions should initially include

  1. STD/HIV prevention in Turkey: planning a sequence of interventions.

    PubMed

    Aral, S O; Fransen, L

    1995-12-01

    This study was initiated to assess which mix of early STD/HIV prevention interventions would potentially be effective, cost-effective and sustainable in Turkey; and to program an intervention sequence to maximize synergy among the interventions. During rapid assessment we: 1) reviewed past issues of 3 leading newspapers; 2) collected information on TV coverage; 3) interviewed key informants including taxicab drivers, hotel employees, grocery store owners, academicians in public health and law, investigators of STD/HIV and reproductive tract infections, and officials in the ministry of health; 4) reviewed available evidence on STD/HIV morbidity, sexual behavior patterns, migration patterns and same/opposite gender sex trade. We found: 1) discrepancies between decision makers' perceptions and social realities with respect to the epidemiology of sexual behavior and STDs, and the state of public health programs; 2) discrepancies between sexual practices and public expression regarding sexual practices; 3) economic, demographic, and political pressures in Turkey and in surrounding countries for the expansion of prostitution; 4) a sexual double standard and gender specific migration patterns which sustain a high demand for commercial sex; 5) patterns of health care seeking behaviors and provision of STD clinical services which indicate other STDs may play a very important role in spread of HIV infection; 6) an important mass media role in opinion formation; 7) consensual denial of risk for the majority based on beliefs embedded in machismo, nationalism and religion, and a resulting marginalization and externalization of STD/HIV risk; 8) high prevalence of syphilis among both Turkish and immigrant female prostitutes in Istanbul (early latent 8 and 13%; late latent 0 and 4%; previous history 9 and 22%) 9) and high rates of syphilis among male prostitutes (early latent 11%, late latent 21% and previous history 58%). We concluded that interventions should initially include

  2. HIV-1 gp140 epitope recognition is influenced by immunoglobulin DH gene segment sequence.

    PubMed

    Wang, Yuge; Kapoor, Pratibha; Parks, Robert; Silva-Sanchez, Aaron; Alam, S Munir; Verkoczy, Laurent; Liao, Hua-Xin; Zhuang, Yingxin; Burrows, Peter; Levinson, Michael; Elgavish, Ada; Cui, Xiangqin; Haynes, Barton F; Schroeder, Harry

    2016-02-01

    Complementarity Determining Region 3 of the immunoglobulin (Ig) H chain (CDR-H3) lies at the center of the antigen-binding site where it often plays a decisive role in antigen recognition and binding. Amino acids encoded by the diversity (DH) gene segment are the main component of CDR-H3. Each DH has the potential to rearrange into one of six DH reading frames (RFs), each of which exhibits a characteristic amino acid hydrophobicity signature that has been conserved among jawed vertebrates by natural selection. A preference for use of RF1 promotes the incorporation of tyrosine into CDR-H3 while suppressing the inclusion of hydrophobic or charged amino acids. To test the hypothesis that these evolutionary constraints on DH sequence influence epitope recognition, we used mice with a single DH that has been altered to preferentially use RF2 or inverted RF1. B cells in these mice produce a CDR-H3 repertoire that is enriched for valine or arginine in place of tyrosine. We serially immunized this panel of mice with gp140 from HIV-1 JR-FL isolate and then used enzyme-linked immunosorbent assay (ELISA) or peptide microarray to assess antibody binding to key or overlapping HIV-1 envelope epitopes. By ELISA, serum reactivity to key epitopes varied by DH sequence. By microarray, sera with Ig CDR-H3s enriched for arginine bound to linear peptides with a greater range of hydrophobicity but had a lower intensity of binding than sera containing Ig CDR-H3s enriched for tyrosine or valine. We conclude that patterns of epitope recognition and binding can be heavily influenced by DH germ line sequence. This may help explain why antibodies in HIV-infected patients must undergo extensive somatic mutation in order to bind to specific viral epitopes and achieve neutralization. PMID:26687685

  3. Evaluation of genotypic prediction of HIV-1 tropism using population sequencing of replicates.

    PubMed

    Ferreira, Joao Leandro de Paula; Coelho, Luana Portes Ozorio; Rodrigues, Rosangela; Cabral, Gabriela Bastos; Cavalcanti, Jaqueline de Souza; Guimaraes, Paula Morena de Souza; Brigido, Luis Fernando de Macedo

    2012-02-01

    Determination of human immunodeficiency virus tropism has contributed to the understanding of the pathogenesis of HIV and is necessary prior to the use of CCR5 antagonists. Replicate V3 sequences may generate different sequences and improve viral tropism prediction. The diversity of HIV was evaluated to access its influence on prediction. Plasma RNA was retro-transcribed and amplified using a one-step protocol, followed by nested PCR and sequencing using an ABI3130XL. Eighty-one patients, 74% male and 26% female, with a median age of 44 years had either a single sequence (n=50) or 2-4 replicates (n=31) evaluated. Most patients (92%) had used multiple anti-retroviral regimens. Tropism prediction was performed using the Geno2pheno clonal option. The number of ambiguous nucleotides, the deduced non-synonymous amino acids at V3 and the genetic distance were quantified. Using a 20% false positive rate (FPR) cut-off, 41/81 (50.6%) was predicted as X4. TCD4 was lower, 226 cells/mm(3) (IQR 82-378), in patients infected with X4; TCD4 for R5 was 324 cells/mm(3) (IQR 200-538, p<0.05). The number of ambiguous nucleotides correlated with a lower FPR value (p<0.0027). Although different sequences may be generated, the number of replicates was not associated to a lower FPR or X4 assignment, and may allow a better prediction of this biological characteristic. Ambiguous nucleotides correlate inversely to a lower FPR.

  4. Characteristic of HIV-1 in V3 loop region based on seroreactivity and amino acid sequences in Thailand.

    PubMed

    Balachandra, Kruavon; Matsuo, Kazuhiro; Sutthent, Ruengpung; Hoisanka, Narin; Boonsarthorn, Naphasawan; Sawanpanyalert, Pathom; Warachit, Paijit; Yamazaki, Shudo; Honda, Mitsuo

    2002-06-01

    The third variable (V3) domain of the envelop (env) protein has been used for determining genetic subtype and phenotypic characteristics of human immunodeficiency virus type 1 (HIV-1) isolates. Based on the seroreactivity of the HIV-1 subtype by V3 peptide binding enzyme immunoassay (EIA) of 351 samples obtained in 1998 from HIV-1 infected individuals and AIDS patients, we found that 283 (80.6%) were subtype E, 20 (5.7%) were subtype B, 28 (8.0%) were cross-reactive between both types and 20 (5.7%) were non-typeable. The degree of seroreactivity of HIV-1 subtype E decreased significantly when the amino acid at the crown of the V3 loop was substituted from a GPGQ motif to GPGR motif. Interestingly, AIDS patients who had V3 sequences of subtype E as GPGR motif had a stronger immunoreactivity to GPGQ motif peptides than to GPGR motif peptides, in contradiction for their proviral sequences. The results suggested that mutations in the V3 loop may lead to a changed immunoreactivity that makes HIV-1 mutants unrecognizable or allow escape from the primary immune response by means of neutralizing sensitivity. In connection with vaccine development, it should be pointed out that the combination of V3 sequencing and peptide EIA could provide a novel approach to obtain a primarily infected virus sequence as a target for a preventive AIDS vaccine.

  5. Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

    PubMed Central

    Meini, Genny; Rossetti, Barbara; Bianco, Claudia; Ceccherini-Silberstein, Francesca; Di Giambenedetto, Simona; Sighinolfi, Laura; Monno, Laura; Castagna, Antonella; Rozera, Gabriella; D'Arminio Monforte, Antonella; Zazzi, Maurizio; De Luca, Andrea; Moroni, M.; Angarano, G.; Antinori, A.; Armignacco, O.; d'Arminio Monforte, A.; Castelli, F.; Cauda, R.; Di Perri, G.; Galli, M.; Iardino, R.; Ippolito, G.; Lazzarin, A.; Perno, C. F.; von Schloesser, F.; Viale, P.; d'Arminio Monforte, A.; Antinori, A.; Castagna, A.; Ceccherini-Silberstein, F.; Cozzi-Lepri, A.; Girardi, E.; Lo Caputo, S.; Mussini, C.; Puoti, M.; Andreoni, M.; Ammassari, A.; Antinori, A.; Balotta, C.; Bonfanti, P.; Bonora, S.; Borderi, M.; Capobianchi, M. R.; Castagna, A.; Ceccherini-Silberstein, F.; Cingolani, A.; Cinque, P.; Cozzi-Lepri, A.; d'Arminio Monforte, A; De Luca, A.; Di Biagio, A.; Girardi, E.; Gianotti, N.; Gori, A.; Guaraldi, G.; Lapadula, G.; Lichtner, M.; Lo Caputo, S.; Madeddu, G.; Maggiolo, F.; Marchetti, G.; Marcotullio, S.; Monno, L.; Mussini, C.; Puoti, M.; Quiros Roldan, E.; Rusconi, S.; Cozzi-Lepri, A.; Cicconi, P.; Fanti, I.; Formenti, T.; Galli, L.; Lorenzini, P.; Giacometti, A.; Costantini, A.; Angarano, G.; Monno, L.; Santoro, C.; Maggiolo, F.; Suardi, C.; Viale, P.; Vanino, E.; Verucchi, G.; Castelli, F.; Quiros Roldan, E.; Minardi, C.; Quirino, T.; Abeli, C.; Manconi, P.E.; Piano, P.; Vecchiet, J.; Falasca, K.; Sighinolfi, L.; Segala, D.; Mazzotta, F.; Lo Caputo, S.; Cassola, G.; Viscoli, G.; Alessandrini, A.; Piscopo, R.; Mazzarello, G.; Mastroianni, C.; Belvisi, V.; Bonfanti, P.; Caramma, I.; Castelli, A. P.; Galli, M.; Lazzarin, A.; Rizzardini, G.; Puoti, M.; d'Arminio Monforte, A.; Ridolfo, A. L.; Piolini, R.; Castagna, A.; Salpietro, S.; Carenzi, L.; Moioli, M. C.; Cicconi, P.; Marchetti, G.; Mussini, C.; Puzzolante, C.; Gori, A.; Lapadula, G.; Abrescia, N.; Chirianni, A.; Guida, M. G.; Gargiulo, M.; Baldelli, F.; Francisci, D.; Parruti, G.; Ursini, T.; Magnani, G.; Ursitti, M. A.; Cauda, R.; Andreoni, M.; Antinori, A.; Vullo, V.; Cingolani, A.; d'Avino, A.; Ammassari, A.; Gallo, L.; Nicastri, E.; Acinapura, R.; Capozzi, M.; Libertone, R.; Tebano, G.; Cattelan, A.; Mura, M. S.; Madeddu, G.; Caramello, P.; Di Perri, G.; Orofino, G. C.; Bonora, S.; Sciandra, M.; Pellizzer, G.; Manfrin, V.

    2014-01-01

    Objectives Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment. Methods HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated. Results Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing. Conclusions HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option. PMID:24155059

  6. Multilocus sequence typing of Cryptococcus neoformans in non-HIV associated cryptococcosis in Nagasaki, Japan.

    PubMed

    Mihara, Tomo; Izumikawa, Koichi; Kakeya, Hiroshi; Ngamskulrungroj, Popchai; Umeyama, Takashi; Takazono, Takahiro; Tashiro, Masato; Nakamura, Shigeki; Imamura, Yoshifumi; Miyazaki, Taiga; Ohno, Hideaki; Yamamoto, Yoshihiro; Yanagihara, Katsunori; Miyzaki, Yoshitsugu; Kohno, Shigeru

    2013-04-01

    Cryptococcosis is primarily caused by two Cryptococcus species, i.e., Cryptococcus neoformans and C. gattii. Both include several genetically diverse subgroups that can be differentiated using various molecular strain typing methods. Since little is known about the molecular epidemiology of the C. neoformans/C. gattii species complex in Japan, we conducted a molecular epidemiological analysis of 35 C. neoformans isolates from non-HIV patients in Nagasaki, Japan and 10 environmental isolates from Thailand. All were analyzed using URA5-restriction fragment length polymorphism (RFLP) and multilocus sequence typing (MLST). Combined sequence data for all isolates were evaluated with the neighbor-joining method. All were found to be serotype A and mating type MATα. Thirty-two of the 35 clinical isolates molecular type VNI, while the three remaining isolates were VNII as determined through the URA5-RFLP method. Thirty-one of the VNI isolates were identified as MLST sequence type (ST) 5, the remaining one was ST 32 and the three VNII isolates were found to be ST 43. All the environmental isolates were identified as molecular type VNI (four MLST ST 5 and six ST 4). Our study shows that C. neoformans isolates in Nagasaki are genetically homogeneous, with most of the isolates being ST 5. PMID:22901045

  7. Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences

    PubMed Central

    Tartaglia, Lawrence J.; Chang, Hui-Wen; Lee, Benjamin C.; Abbink, Peter; Ng’ang’a, David; Boyd, Michael; Lavine, Christy L.; Lim, So-Yon; Sanisetty, Srisowmya; Whitney, James B.; Seaman, Michael S.; Rolland, Morgane; Tovanabutra, Sodsai; Ananworanich, Jintanat; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Barouch, Dan H.

    2016-01-01

    Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection. PMID:26849216

  8. HIV

    PubMed Central

    Chawla, Sumit; Sahoo, Soumya Swaroop; Jain, Rambilas; Khanna, Pardeep; Mehta, Bharti; Singh, Inderjeet

    2014-01-01

    Getting to zero: zero new HIV infections, zero deaths from AIDS-related illness, zero discrimination is the theme of World AIDS Day 2012. Given the spread of the epidemic today, getting to zero may sound difficult, but significant progress is underway. The total annual loss for the entire country due to HIV is 7% of GDP, which exceeds India’s annual health expenditure in 2004. The additional loss due to loss of labor income and increased medical expenditure as measured by the external transfers, account for 5% of the country’s health expenditure and 0.23% of GDP. Given that the HIV incidence rate is only 0.27% in India, these losses are quite staggering. Despite the remarkable achievements in development of anti-retroviral therapies against HIV and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. PMID:24056755

  9. Structure-function studies of HIV-1: influence of long terminal repeat U3 region sequences on virus production.

    PubMed

    Velpandi, A; Nagashunmugam, T; Otsuka, T; Cartas, M; Srinivasan, A

    1992-06-01

    DNA sequence analyses of several human immunodeficiency virus (HIV) isolates revealed extensive genetic diversity in the env gene and, to a lesser extent, in other regions of the viral genome, including the long terminal repeat (LTR) sequences. Since the LTRs contain elements responsible for the control of transcription, the difference in the LTR region may play a crucial role in the overall replication rate of HIV. To evaluate the role of the LTR, we have constructed a number of infectious hybrid HIV molecular clones containing LTRs from different proviral DNAs linked to the body of the viral genome, and analyzed them in a transient expression system. Both parental and hybrid proviral DNAs were transfected into human rhabdomyosarcoma cells for monitoring virus production. Proviral DNA designate pZ6 (HIVZr6) showed a high level of virus in the medium of the transfected culture in comparison to the pHXB2 (HIVHTLV-III) and pARV (HIVSF-2) DNAs. Hybrid proviral DNAs containing viral genes from pZ6, linked to LTR U3 sequences of pHXB2 and pARV at the 5' end, showed virus production similar to the levels observed with pZ6. These results indicate that the extent of virus production does not correlate with the LTR U3 sequences, and may involve other regions of the viral genome.

  10. Dynamic regulation of HIV-1 mRNA populations analyzed by single-molecule enrichment and long-read sequencing

    PubMed Central

    Ocwieja, Karen E.; Sherrill-Mix, Scott; Mukherjee, Rithun; Custers-Allen, Rebecca; David, Patricia; Brown, Michael; Wang, Susana; Link, Darren R.; Olson, Jeff; Travers, Kevin; Schadt, Eric; Bushman, Frederic D.

    2012-01-01

    Alternative RNA splicing greatly expands the repertoire of proteins encoded by genomes. Next-generation sequencing (NGS) is attractive for studying alternative splicing because of the efficiency and low cost per base, but short reads typical of NGS only report mRNA fragments containing one or few splice junctions. Here, we used single-molecule amplification and long-read sequencing to study the HIV-1 provirus, which is only 9700 bp in length, but encodes nine major proteins via alternative splicing. Our data showed that the clinical isolate HIV-189.6 produces at least 109 different spliced RNAs, including a previously unappreciated ∼1 kb class of messages, two of which encode new proteins. HIV-1 message populations differed between cell types, longitudinally during infection, and among T cells from different human donors. These findings open a new window on a little studied aspect of HIV-1 replication, suggest therapeutic opportunities and provide advanced tools for the study of alternative splicing. PMID:22923523

  11. The highly conserved codon following the slippery sequence supports -1 frameshift efficiency at the HIV-1 frameshift site.

    PubMed

    Mathew, Suneeth F; Crowe-McAuliffe, Caillan; Graves, Ryan; Cardno, Tony S; McKinney, Cushla; Poole, Elizabeth S; Tate, Warren P

    2015-01-01

    HIV-1 utilises -1 programmed ribosomal frameshifting to translate structural and enzymatic domains in a defined proportion required for replication. A slippery sequence, U UUU UUA, and a stem-loop are well-defined RNA features modulating -1 frameshifting in HIV-1. The GGG glycine codon immediately following the slippery sequence (the 'intercodon') contributes structurally to the start of the stem-loop but has no defined role in current models of the frameshift mechanism, as slippage is inferred to occur before the intercodon has reached the ribosomal decoding site. This GGG codon is highly conserved in natural isolates of HIV. When the natural intercodon was replaced with a stop codon two different decoding molecules-eRF1 protein or a cognate suppressor tRNA-were able to access and decode the intercodon prior to -1 frameshifting. This implies significant slippage occurs when the intercodon is in the (perhaps distorted) ribosomal A site. We accommodate the influence of the intercodon in a model of frame maintenance versus frameshifting in HIV-1. PMID:25807539

  12. Genetic shift of env V3 loop viral sequences in patients with HIV-associated neurocognitive disorder during antiretroviral therapy.

    PubMed

    Eggers, Christian; Müller, Oliver; Thordsen, Ingo; Schreiber, Michael; Methner, Axel

    2013-12-01

    The development of human immunodeficiency virus type 1 (HIV)-associated neurocognitive disorder (HAND) involves the adaptation of viral sequences coding for the V3 loop of the env protein. The plasma and cerebrospinal fluid (CSF) may contain viral populations from various cellular sources and with differing pathogenicity. Combination antiretroviral therapy (cART) may alter the relative abundance of these viral populations, leading to a genetic shift. We characterized plasma and CNS viral populations prior to and during cART and relate the findings to viral elimination kinetics and the clinical phenotype. Longitudinal plasma and CSF samples of five chronically infected HIV patients, four of whom had HAND, and one seroconverter were analyzed for V3 sequences by RT-PCR and sequence analysis. In the chronically infected patients, pre-cART plasma and CSF viral sequences were different irrespective of viral elimination kinetics and clinical phenotype. cART induced replacement of plasma viral populations in all subjects. CSF viral populations underwent a clear genetic shift in some patients but remained stable in others. This was not dependent on the presence of HAND. The genetic shift of CSF V3 sequences was absent in the two subjects whose CSF viral load initially increased during cART. In one patient, pre- and post-treatment CSF sequences were closely related to the post-treatment plasma sequences, suggesting a common cellular source. We found heterogeneous patterns of genetic compartmentalization and genetic shift over time. Although these did not closely match viral elimination kinetics and clinical phenotype, the results imply different patterns of the dynamics and relative contribution of compartment-specific virus populations in chronic HIV infection.

  13. Characterization of HIV Transmission in South-East Austria.

    PubMed

    Hoenigl, Martin; Chaillon, Antoine; Kessler, Harald H; Haas, Bernhard; Stelzl, Evelyn; Weninger, Karin; Little, Susan J; Mehta, Sanjay R

    2016-01-01

    To gain deeper insight into the epidemiology of HIV-1 transmission in South-East Austria we performed a retrospective analysis of 259 HIV-1 partial pol sequences obtained from unique individuals newly diagnosed with HIV infection in South-East Austria from 2008 through 2014. After quality filtering, putative transmission linkages were inferred when two sequences were ≤1.5% genetically different. Multiple linkages were resolved into putative transmission clusters. Further phylogenetic analyses were performed using BEAST v1.8.1. Finally, we investigated putative links between the 259 sequences from South-East Austria and all publicly available HIV polymerase sequences in the Los Alamos National Laboratory HIV sequence database. We found that 45.6% (118/259) of the sampled sequences were genetically linked with at least one other sequence from South-East Austria forming putative transmission clusters. Clustering individuals were more likely to be men who have sex with men (MSM; p<0.001), infected with subtype B (p<0.001) or subtype F (p = 0.02). Among clustered males who reported only heterosexual (HSX) sex as an HIV risk, 47% clustered closely with MSM (either as pairs or within larger MSM clusters). One hundred and seven of the 259 sequences (41.3%) from South-East Austria had at least one putative inferred linkage with sequences from a total of 69 other countries. In conclusion, analysis of HIV-1 sequences from newly diagnosed individuals residing in South-East Austria revealed a high degree of national and international clustering mainly within MSM. Interestingly, we found that a high number of heterosexual males clustered within MSM networks, suggesting either linkage between risk groups or misrepresentation of sexual risk behaviors by subjects.

  14. Characterization of HIV Transmission in South-East Austria

    PubMed Central

    Kessler, Harald H.; Haas, Bernhard; Stelzl, Evelyn; Weninger, Karin; Little, Susan J.; Mehta, Sanjay R.

    2016-01-01

    To gain deeper insight into the epidemiology of HIV-1 transmission in South-East Austria we performed a retrospective analysis of 259 HIV-1 partial pol sequences obtained from unique individuals newly diagnosed with HIV infection in South-East Austria from 2008 through 2014. After quality filtering, putative transmission linkages were inferred when two sequences were ≤1.5% genetically different. Multiple linkages were resolved into putative transmission clusters. Further phylogenetic analyses were performed using BEAST v1.8.1. Finally, we investigated putative links between the 259 sequences from South-East Austria and all publicly available HIV polymerase sequences in the Los Alamos National Laboratory HIV sequence database. We found that 45.6% (118/259) of the sampled sequences were genetically linked with at least one other sequence from South-East Austria forming putative transmission clusters. Clustering individuals were more likely to be men who have sex with men (MSM; p<0.001), infected with subtype B (p<0.001) or subtype F (p = 0.02). Among clustered males who reported only heterosexual (HSX) sex as an HIV risk, 47% clustered closely with MSM (either as pairs or within larger MSM clusters). One hundred and seven of the 259 sequences (41.3%) from South-East Austria had at least one putative inferred linkage with sequences from a total of 69 other countries. In conclusion, analysis of HIV-1 sequences from newly diagnosed individuals residing in South-East Austria revealed a high degree of national and international clustering mainly within MSM. Interestingly, we found that a high number of heterosexual males clustered within MSM networks, suggesting either linkage between risk groups or misrepresentation of sexual risk behaviors by subjects. PMID:26967154

  15. Comparison of a high-resolution melting assay to next-generation sequencing for analysis of HIV diversity.

    PubMed

    Cousins, Matthew M; Ou, San-San; Wawer, Maria J; Munshaw, Supriya; Swan, David; Magaret, Craig A; Mullis, Caroline E; Serwadda, David; Porcella, Stephen F; Gray, Ronald H; Quinn, Thomas C; Donnell, Deborah; Eshleman, Susan H; Redd, Andrew D

    2012-09-01

    Next-generation sequencing (NGS) has recently been used for analysis of HIV diversity, but this method is labor-intensive, costly, and requires complex protocols for data analysis. We compared diversity measures obtained using NGS data to those obtained using a diversity assay based on high-resolution melting (HRM) of DNA duplexes. The HRM diversity assay provides a single numeric score that reflects the level of diversity in the region analyzed. HIV gag and env from individuals in Rakai, Uganda, were analyzed in a previous study using NGS (n = 220 samples from 110 individuals). Three sequence-based diversity measures were calculated from the NGS sequence data (percent diversity, percent complexity, and Shannon entropy). The amplicon pools used for NGS were analyzed with the HRM diversity assay. HRM scores were significantly associated with sequence-based measures of HIV diversity for both gag and env (P < 0.001 for all measures). The level of diversity measured by the HRM diversity assay and NGS increased over time in both regions analyzed (P < 0.001 for all measures except for percent complexity in gag), and similar amounts of diversification were observed with both methods (P < 0.001 for all measures except for percent complexity in gag). Diversity measures obtained using the HRM diversity assay were significantly associated with those from NGS, and similar increases in diversity over time were detected by both methods. The HRM diversity assay is faster and less expensive than NGS, facilitating rapid analysis of large studies of HIV diversity and evolution.

  16. Hepatitis C Virus (HCV) NS3 sequence diversity and antiviral resistance-associated variant frequency in HCV/HIV coinfection.

    PubMed

    Jabara, Cassandra B; Hu, Fengyu; Mollan, Katie R; Williford, Sara E; Menezes, Prema; Yang, Yan; Eron, Joseph J; Fried, Michael W; Hudgens, Michael G; Jones, Corbin D; Swanstrom, Ronald; Lemon, Stanley M

    2014-10-01

    HIV coinfection accelerates disease progression in chronic hepatitis C and reduces sustained antiviral responses (SVR) to interferon-based therapy. New direct-acting antivirals (DAAs) promise higher SVR rates, but the selection of preexisting resistance-associated variants (RAVs) may lead to virologic breakthrough or relapse. Thus, pretreatment frequencies of RAVs are likely determinants of treatment outcome but typically are below levels at which the viral sequence can be accurately resolved. Moreover, it is not known how HIV coinfection influences RAV frequency. We adopted an accurate high-throughput sequencing strategy to compare nucleotide diversity in HCV NS3 protease-coding sequences in 20 monoinfected and 20 coinfected subjects with well-controlled HIV infection. Differences in mean pairwise nucleotide diversity (π), Tajima's D statistic, and Shannon entropy index suggested that the genetic diversity of HCV is reduced in coinfection. Among coinfected subjects, diversity correlated positively with increases in CD4(+) T cells on antiretroviral therapy, suggesting T cell responses are important determinants of diversity. At a median sequencing depth of 0.084%, preexisting RAVs were readily identified. Q80K, which negatively impacts clinical responses to simeprevir, was encoded by more than 99% of viral RNAs in 17 of the 40 subjects. RAVs other than Q80K were identified in 39 of 40 subjects, mostly at frequencies near 0.1%. RAV frequency did not differ significantly between monoinfected and coinfected subjects. We conclude that HCV genetic diversity is reduced in patients with well-controlled HIV infection, likely reflecting impaired T cell immunity. However, RAV frequency is not increased and should not adversely influence the outcome of DAA therapy.

  17. HIV-1 Suppressive Sequences Are Modulated by Rev Transport of Unspliced RNA and Are Required for Efficient HIV-1 Production

    PubMed Central

    Noguchi, Kousei; Ishibashi, Keisuke; Miyokawa, Kaori; Hokari, Manami; Kanno, Tomoyuki; Hirano, Tomoya; Yamamoto, Norio; Takaku, Hiroshi

    2012-01-01

    The unspliced human immunodeficiency virus type 1 (HIV-1) RNAs are translated as Gag and Gag-Pol polyproteins or packaged as genomes into viral particles. Efficient translation is necessary before the transition to produce infective virions. The viral protein Rev exports all intron-containing viral RNAs; however, it also appears to enhance translation. Cellular microRNAs target cellular and viral mRNAs to silence their translation and enrich them at discrete cytoplasmic loci that overlap with the putative interim site of Gag and the genome. Here, we analyzed how Rev-mediated transport and the splicing status of the mRNA influenced the silencing status imposed by microRNA. Through identification and mutational analysis of the silencing sites in the HIV-1 genome, we elucidated the effect of silencing on virus production. Renilla luciferase mRNA, which contains a let-7 targeting site in its 3′ untranslated region, was mediated when it was transported by Rev and not spliced, but it was either not mediated when it was spliced even in a partial way or it was Rev-independent. The silencing sites in the pol and env-nef regions of the HIV-1 genome, which were repressed in T cells and other cell lines, were Drosha-dependent and could also be modulated by Rev in an unspliced state. Mutant viruses that contained genomic mutations that reflect alterations to show more derepressive effects in the 3′ untranslated region of the Renilla luciferase gene replicated more slowly than wild-type virus. These findings yield insights into the HIV-1 silencing sites that might allow the genome to avoid translational machinery and that might be utilized in coordinating virus production during initial virus replication. However, the function of Rev to modulate the silencing sites of unspliced RNAs would be advantageous for the efficient translation that is required to support protein production prior to viral packaging and particle production. PMID:23251516

  18. HIV-1 Nef sequence and functional compartmentalization in the gut is not due to differential cytotoxic T lymphocyte selective pressure.

    PubMed

    Lewis, Martha J; Frohnen, Patricia; Ibarrondo, F Javier; Reed, Diane; Iyer, Varun; Ng, Hwee L; Elliott, Julie; Yang, Otto O; Anton, Peter

    2013-01-01

    The gut is the largest lymphoid organ in the body and a site of active HIV-1 replication and immune surveillance. The gut is a reservoir of persistent infection in some individuals with fully suppressed plasma viremia on combination antiretroviral therapy (cART) although the cause of this persistence is unknown. The HIV-1 accessory protein Nef contributes to persistence through multiple functions including immune evasion and increasing infectivity. Previous studies showed that Nef's function is shaped by cytotoxic T lymphocyte (CTL) responses and that there are distinct populations of Nef within tissue compartments. We asked whether Nef's sequence and/or function are compartmentalized in the gut and how compartmentalization relates to local CTL immune responses. Primary nef quasispecies from paired plasma and sigmoid colon biopsies from chronically infected subjects not on therapy were sequenced and cloned into Env(-) Vpu(-) pseudotyped reporter viruses. CTL responses were mapped by IFN-γ ELISpot using expanded CD8+ cells from blood and gut with pools of overlapping peptides covering the entire HIV proteome. CD4 and MHC Class I Nef-mediated downregulation was measured by flow cytometry. Multiple tests indicated compartmentalization of nef sequences in 5 of 8 subjects. There was also compartmentalization of function with MHC Class I downregulation relatively well preserved, but significant loss of CD4 downregulation specifically by gut quasispecies in 5 of 7 subjects. There was no compartmentalization of CTL responses in 6 of 8 subjects, and the selective pressure on quasispecies correlated with the magnitude CTL response regardless of location. These results demonstrate that Nef adapts via diverse pathways to local selective pressures within gut mucosa, which may be predominated by factors other than CTL responses such as target cell availability. The finding of a functionally distinct population within gut mucosa offers some insight into how HIV-1 may persist in

  19. Adaptation of CD8 T cell responses to changing HIV-1 sequences in a cohort of HIV-1 infected individuals not selected for a certain HLA allele.

    PubMed

    Roider, Julia; Kalteis, Anna-Lena; Vollbrecht, Thomas; Gloning, Lisa; Stirner, Renate; Henrich, Nadja; Bogner, Johannes R; Draenert, Rika

    2013-01-01

    HIV evades CD8 T cell mediated pressure by viral escape mutations in targeted CD8 T cell epitopes. A viral escape mutation can lead to a decline of the respective CD8 T cell response. Our question was what happened after the decline of a CD8 T cell response and - in the case of viral escape - if a new CD8 T cell response towards the mutated antigen could be generated in a population not selected for certain HLA alleles. We studied 19 antiretroviral-naïve HIV-1 infected individuals with different disease courses longitudinally. A median number of 12 (range 2-24) CD8 T cell responses towards Gag and Nef were detected per study subject. A total of 30 declining CD8 T cell responses were studied in detail and viral sequence analyses showed amino acid changes in 25 (83%) of these. Peptide titration assays and definition of optimal CD8 T cell epitopes revealed 12 viral escape mutations with one de-novo response (8%). The de-novo response, however, showed less effector functions than the original CD8 T cell response. In addition we identified 4 shifts in immunodominance. For one further shift in immunodominance, the mutations occurred outside the optimal epitope and might represent processing changes. Interestingly, four adaptations to the virus (the de-novo response and 3 shifts in immunodominance) occurred in the group of chronically infected progressors. None of the subjects with adaptation to the changing virus carried the HLA alleles B57, B*58:01 or B27. Our results show that CD8 T cell responses adapt to the mutations of HIV. However it was limited to only 20% (5 out of 25) of the epitopes with viral sequence changes in a cohort not expressing protective HLA alleles.

  20. Stockpile Stewardship: Los Alamos

    SciTech Connect

    McMillan, Charlie; Morgan, Nathanial; Goorley, Tom; Merrill, Frank; Funk, Dave; Korzekwa, Deniece; Laintz, Ken

    2012-01-26

    "Heritage of Science" is a short video that highlights the Stockpile Stewardship program at Los Alamos National Laboratory. Stockpile Stewardship was conceived in the early 1990s as a national science-based program that could assure the safety, security, and effectiveness of the U.S. nuclear deterrent without the need for full-scale underground nuclear testing. This video was produced by Los Alamos National Laboratory for screening at the Lab's Bradbury Science Museum in Los Alamos, NM and is narrated by science correspondent Miles O'Brien.

  1. Stockpile Stewardship: Los Alamos

    ScienceCinema

    McMillan, Charlie; Morgan, Nathanial; Goorley, Tom; Merrill, Frank; Funk, Dave; Korzekwa, Deniece; Laintz, Ken

    2016-07-12

    "Heritage of Science" is a short video that highlights the Stockpile Stewardship program at Los Alamos National Laboratory. Stockpile Stewardship was conceived in the early 1990s as a national science-based program that could assure the safety, security, and effectiveness of the U.S. nuclear deterrent without the need for full-scale underground nuclear testing. This video was produced by Los Alamos National Laboratory for screening at the Lab's Bradbury Science Museum in Los Alamos, NM and is narrated by science correspondent Miles O'Brien.

  2. Certification assays for HIV-1-based vectors: frequent passage of gag sequences without evidence of replication-competent viruses.

    PubMed

    Sastry, Lakshmi; Xu, Yi; Johnson, Terry; Desai, Kunal; Rissing, David; Marsh, Jonathan; Cornetta, Kenneth

    2003-11-01

    A principal concern regarding the safety of HIV-1-based vectors is replication-competent lentivirus (RCL). We have developed two PCR assays for detecting RCL; the first detects recombination between gag regions in the transfer vector and the packaging construct (sensitivity of detection approximately 10-100 copies of target sequence). The second assay uses real-time PCR to detect vesicular stomatitis virus glycoprotein (VSVG) envelope DNA (sensitivity approximately 5-50 VSVG sequences). In an attempt to amplify any RCL, test vectors were used to transduce C8166 and 293 cells, which were then screened weekly for 3 weeks. Psi-gag recombinants were routinely detected (20 of 21 analyses) in four transductions using the RRL-CMV-GFP vector. In contrast, VSVG sequences were detected only once in 21 analyses. Interestingly, p24 levels (as measured by ELISA) were occasionally detectable after 3 weeks of culture. To determine if a true RCL was present, 21-day cell-free medium was used to transduce naïve cells. No evidence of psi-gag or VSVG transfer was detected, indicating that the recombination events were insufficient to reconstitute a true RCL. These findings have important implications for the design and safety of HIV-1-based vectors intended for clinical applications. PMID:14599817

  3. Subtype-independent near full-length HIV-1 genome sequencing and assembly to be used in large molecular epidemiological studies and clinical management

    PubMed Central

    Grossmann, Sebastian; Nowak, Piotr; Neogi, Ujjwal

    2015-01-01

    Introduction HIV-1 near full-length genome (HIV-NFLG) sequencing from plasma is an attractive multidimensional tool to apply in large-scale population-based molecular epidemiological studies. It also enables genotypic resistance testing (GRT) for all drug target sites allowing effective intervention strategies for control and prevention in high-risk population groups. Thus, the main objective of this study was to develop a simplified subtype-independent, cost- and labour-efficient HIV-NFLG protocol that can be used in clinical management as well as in molecular epidemiological studies. Methods Plasma samples (n=30) were obtained from HIV-1B (n=10), HIV-1C (n=10), CRF01_AE (n=5) and CRF01_AG (n=5) infected individuals with minimum viral load >1120 copies/ml. The amplification was performed with two large amplicons of 5.5 kb and 3.7 kb, sequenced with 17 primers to obtain HIV-NFLG. GRT was validated against ViroSeq™ HIV-1 Genotyping System. Results After excluding four plasma samples with low-quality RNA, a total of 26 samples were attempted. Among them, NFLG was obtained from 24 (92%) samples with the lowest viral load being 3000 copies/ml. High (>99%) concordance was observed between HIV-NFLG and ViroSeq™ when determining the drug resistance mutations (DRMs). The N384I connection mutation was additionally detected by NFLG in two samples. Conclusions Our high efficiency subtype-independent HIV-NFLG is a simple and promising approach to be used in large-scale molecular epidemiological studies. It will facilitate the understanding of the HIV-1 pandemic population dynamics and outline effective intervention strategies. Furthermore, it can potentially be applicable in clinical management of drug resistance by evaluating DRMs against all available antiretrovirals in a single assay. PMID:26115688

  4. Conserved sequences in the current strains of HIV-1 subtype A in Russia are effectively targeted by artificial RNAi in vitro.

    PubMed

    Tchurikov, Nickolai A; Fedoseeva, Daria M; Gashnikova, Natalya M; Sosin, Dmitri V; Gorbacheva, Maria A; Alembekov, Ildar R; Chechetkin, Vladimir R; Kravatsky, Yuri V; Kretova, Olga V

    2016-05-25

    Highly active antiretroviral therapy has greatly reduced the morbidity and mortality of AIDS. However, many of the antiretroviral drugs are toxic with long-term use, and all currently used anti-HIV agents generate drug-resistant mutants. Therefore, there is a great need for new approaches to AIDS therapy. RNAi is a powerful means of inhibiting HIV-1 production in human cells. We propose to use RNAi for gene therapy of HIV/AIDS. Previously we identified a number of new biologically active siRNAs targeting several moderately conserved regions in HIV-1 transcripts. Here we analyze the heterogeneity of nucleotide sequences in three RNAi targets in sequences encoding the reverse transcriptase and integrase domains of current isolates of HIV-1 subtype A in Russia. These data were used to generate genetic constructs expressing short hairpin RNAs 28-30-bp in length that could be processed in cells into siRNAs. After transfection of the constructs we observed siRNAs that efficiently attacked the selected targets. We expect that targeting several viral genes important for HIV-1 reproduction will help overcome the problem of viral adaptation and will prevent the appearance of RNAi escape mutants in current virus strains, an important feature of gene therapy of HIV/AIDS.

  5. Multiplexed next-generation sequencing and de novo assembly to obtain near full-length HIV-1 genome from plasma virus.

    PubMed

    Aralaguppe, Shambhu G; Siddik, Abu Bakar; Manickam, Ashokkumar; Ambikan, Anoop T; Kumar, Milner M; Fernandes, Sunjay Jude; Amogne, Wondwossen; Bangaruswamy, Dhinoth K; Hanna, Luke Elizabeth; Sonnerborg, Anders; Neogi, Ujjwal

    2016-10-01

    Analysing the HIV-1 near full-length genome (HIV-NFLG) facilitates new understanding into the diversity of virus population dynamics at individual or population level. In this study we developed a simple but high-throughput next generation sequencing (NGS) protocol for HIV-NFLG using clinical specimens and validated the method against an external quality control (EQC) panel. Clinical specimens (n=105) were obtained from three cohorts from two highly conserved HIV-1C epidemics (India and Ethiopia) and one diverse epidemic (Sweden). Additionally an EQC panel (n=10) was used to validate the protocol. HIV-NFLG was performed amplifying the HIV-genome (Gag-to-nef) in two fragments. NGS was performed using the Illumina HiSeq2500 after multiplexing 24 samples, followed by de novo assembly in Iterative Virus Assembler or VICUNA. Subtyping was carried out using several bioinformatics tools. Amplification of HIV-NFLG has 90% (95/105) success-rate in clinical specimens. NGS was successful in all clinical specimens (n=45) and EQA samples (n=10) attempted. The mean error for mutations for the EQC panel viruses were <1%. Subtyping identified two as A1C recombinant. Our results demonstrate the feasibility of a simple NGS-based HIV-NFLG that can potentially be used in the molecular surveillance for effective identification of subtypes and transmission clusters for operational public health intervention.

  6. HIV-1 sequence evolution in vivo after superinfection with three viral strains

    PubMed Central

    Kozaczynska, Karolina; Cornelissen, Marion; Reiss, Peter; Zorgdrager, Fokla; van der Kuyl, Antoinette C

    2007-01-01

    With millions of people infected worldwide, the evolution of HIV-1 in vivo has been the subject of much research. Although recombinant viruses were detected early in the epidemic, evidence that HIV-1 dual infections really occurred came much later. Dual infected patients, consisting of coinfected (second infection before seroconversion) and superinfected (second infection after seroconversion) individuals, opened up a new area of HIV-1 evolution studies. Here, we describe the in-depth analysis of HIV-1 over time in a patient twice superinfected with HIV-1, first with a subtype B (B2) strain and then with CRF01_AE after initial infection with a subtype B (B1) strain. The nucleotide evolution of gag and env-V3 of the three strains followed a similar pattern: a very low substitution rate in the first 2–3 years of infection, with an increase in synonymous substitutions thereafter. Convergent evolution at the protein level was rare: only a single amino acid in a gag p24 epitope showed convergence in the subtype B strains. Reversal of CTL-epitope mutations were also rare, and did not converge. Recombinant viruses were observed between the two subtype B strains. Luciferase-assays suggested that the CRF01_AE long terminal repeat (LTR) constituted the strongest promoter, but this was not reflected in the plasma viral load. Specific real-time PCR assays based upon the env gene showed that strain B2 and CRF01_AE RNA was present in equal amounts, while levels of strain B1 were 100-fold lower. All three strains were detected in seminal plasma, suggesting that simultaneous transmission is possible. PMID:17716368

  7. Relative Resistance of HLA-B to Downregulation by Naturally Occurring HIV-1 Nef Sequences

    PubMed Central

    Mahiti, Macdonald; Toyoda, Mako; Jia, Xiaofei; Kuang, Xiaomei T.; Mwimanzi, Francis; Mwimanzi, Philip; Walker, Bruce D.; Xiong, Yong; Brumme, Zabrina L.; Brockman, Mark A.

    2016-01-01

    ABSTRACT HIV-1 Nef binds to the cytoplasmic region of HLA-A and HLA-B and downregulates these molecules from the surface of virus-infected cells, thus evading immune detection by CD8+ T cells. Polymorphic residues within the HLA cytoplasmic region may affect Nef’s downregulation activity. However, the effects of HLA polymorphisms on recognition by primary Nef isolates remain elusive, as do the specific Nef regions responsible for downregulation of HLA-A versus HLA-B. Here, we examined 46 Nef clones isolated from chronically HIV-1 subtype B-infected subjects for their ability to downregulate various HLA-A, HLA-B, and HLA-C molecules on the surface of virus-infected cells. Overall, HLA-B exhibited greater resistance to Nef-mediated downregulation than HLA-A, regardless of the cell type examined. As expected, no Nef clone downregulated HLA-C. Importantly, the differential abilities of patient-derived Nef clones to downregulate HLA-A and HLA-B correlated inversely with the sensitivities of HIV-infected target cells to recognition by effector cells expressing an HIV-1 Gag-specific T cell receptor. Nef codon function analysis implicated amino acid variation at position 202 (Nef-202) in differentially affecting the ability to downregulate HLA-A and HLA-B, an observation that was subsequently confirmed by experiments using Nef mutants constructed by site-directed mutagenesis. The in silico and mutagenesis analyses further suggested that Nef-202 may interact with the C-terminal Cys-Lys-Val residues of HLA-A, which are absent in HLA-B. Taken together, the results show that natural polymorphisms within Nef modulate its interaction with natural polymorphisms in the HLA cytoplasmic tails, thereby affecting the efficiency of HLA downregulation and consequent recognition by HIV-specific T cells. These results thus extend our understanding of this complex pathway of retroviral immune evasion. PMID:26787826

  8. Los Alamos offers Fellowships

    NASA Astrophysics Data System (ADS)

    Los Alamos National Laboratory in New Mexico is calling for applications for postdoctoral appointments and research fellowships. The positions are available in geoscience as well as other scientific disciplines.The laboratory, which is operated by the University of California for the Department of Energy, awards J. Robert Oppenheimer Research Fellowships to scientists that either have or will soon complete doctoral degrees. The appointments are for two years, are renewable for a third year, and carry a stipend of $51,865 per year. Potential applicants should send a resume or employment application and a statement of research goals to Carol M. Rich, Div. 89, Human Resources Development Division, MS P290, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 by mid-November.

  9. Short Communication: Investigating a Chain of HIV Transmission Events Due to Homosexual Exposure and Blood Transfusion Based on a Next Generation Sequencing Method.

    PubMed

    Zhao, Qi; Zhang, Chen; Jiang, Yan; Wen, Yujie; Pan, Pinliang; Li, Yang; Zhang, Guiyun; Zhang, Lei; Qiu, Maofeng

    2015-12-01

    This study investigates a chain of HIV transmission events due to homosexual exposure and blood transfusion in China. The MiSeq platform, a next generation sequencing (NGS) system, was used to obtain genetic details of the HIV-1 env region (336 base pairs). Evolutionary analysis combined with epidemiologic evidence suggests a transmission chain from patient T3 to T2 through homosexual exposure and subsequently to T1 through blood transfusion. More importantly, a phylogenetic study suggested a likely genetic bottleneck for HIV in homosexual transmission from T3 to T2, while T1 inherited the majority of variants from T2. The result from the MiSeq platform is consistent with findings from the epidemiologic survey. The MiSeq platform is a powerful tool for tracing HIV transmissions and intrapersonal evolution.

  10. Analysis of 454 sequencing error rate, error sources, and artifact recombination for detection of Low-frequency drug resistance mutations in HIV-1 DNA

    PubMed Central

    2013-01-01

    Background 454 sequencing technology is a promising approach for characterizing HIV-1 populations and for identifying low frequency mutations. The utility of 454 technology for determining allele frequencies and linkage associations in HIV infected individuals has not been extensively investigated. We evaluated the performance of 454 sequencing for characterizing HIV populations with defined allele frequencies. Results We constructed two HIV-1 RT clones. Clone A was a wild type sequence. Clone B was identical to clone A except it contained 13 introduced drug resistant mutations. The clones were mixed at ratios ranging from 1% to 50% and were amplified by standard PCR conditions and by PCR conditions aimed at reducing PCR-based recombination. The products were sequenced using 454 pyrosequencing. Sequence analysis from standard PCR amplification revealed that 14% of all sequencing reads from a sample with a 50:50 mixture of wild type and mutant DNA were recombinants. The majority of the recombinants were the result of a single crossover event which can happen during PCR when the DNA polymerase terminates synthesis prematurely. The incompletely extended template then competes for primer sites in subsequent rounds of PCR. Although less often, a spectrum of other distinct crossover patterns was also detected. In addition, we observed point mutation errors ranging from 0.01% to 1.0% per base as well as indel (insertion and deletion) errors ranging from 0.02% to nearly 50%. The point errors (single nucleotide substitution errors) were mainly introduced during PCR while indels were the result of pyrosequencing. We then used new PCR conditions designed to reduce PCR-based recombination. Using these new conditions, the frequency of recombination was reduced 27-fold. The new conditions had no effect on point mutation errors. We found that 454 pyrosequencing was capable of identifying minority HIV-1 mutations at frequencies down to 0.1% at some nucleotide positions. Conclusion

  11. The Effect of Clade-Specific Sequence Polymorphisms on HIV-1 Protease Activity and Inhibitor Resistance Pathways

    SciTech Connect

    Bandaranayake, Rajintha M.; Kolli, Madhavi; King, Nancy M.; Nalivaika, Ellen A.; Heroux, Annie; Kakizawa, Junko; Sugiura, Wataru; Schiffer, Celia A.

    2010-09-08

    The majority of HIV-1 infections around the world result from non-B clade HIV-1 strains. The CRF01{_}AE (AE) strain is seen principally in Southeast Asia. AE protease differs by {approx}10% in amino acid sequence from clade B protease and carries several naturally occurring polymorphisms that are associated with drug resistance in clade B. AE protease has been observed to develop resistance through a nonactive-site N88S mutation in response to nelfinavir (NFV) therapy, whereas clade B protease develops both the active-site mutation D30N and the nonactive-site mutation N88D. Structural and biochemical studies were carried out with wild-type and NFV-resistant clade B and AE protease variants. The relationship between clade-specific sequence variations and pathways to inhibitor resistance was also assessed. AE protease has a lower catalytic turnover rate than clade B protease, and it also has weaker affinity for both NFV and darunavir (DRV). This weaker affinity may lead to the nonactive-site N88S variant in AE, which exhibits significantly decreased affinity for both NFV and DRV. The D30N/N88D mutations in clade B resulted in a significant loss of affinity for NFV and, to a lesser extent, for DRV. A comparison of crystal structures of AE protease shows significant structural rearrangement in the flap hinge region compared with those of clade B protease and suggests insights into the alternative pathways to NFV resistance. In combination, our studies show that sequence polymorphisms within clades can alter protease activity and inhibitor binding and are capable of altering the pathway to inhibitor resistance.

  12. Detection of GB virus C genomic sequence in the cerebrospinal fluid of a HIV-infected patient in China: a case report and literature review.

    PubMed

    Liu, Z; Zhang, Y; Wei, F; Xu, M; Mou, D; Zhang, T; Li, W; Chen, D; Wu, H

    2016-01-01

    Hepatitis G virus or GB virus C (GBV-C) is a human virus of the Flaviviridae family that is structurally and epidemiologically closest to hepatitis C virus, but replicates primarily in lymphocytes. Co-infection with GBV-C has been reported to confer beneficial outcomes in some HIV-positive patients. Up to now, however, studies on GBV-C infection in the central nervous system (CNS) of HIV-infected patient have rarely been reported. Herein, we report on a 32-year-old HIV-1-infected patient with cerebral toxoplasmosis and fungal encephalitis. GBV-C viral loads were detected in CSF by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), and the results showed that GBV-C viral load was 6·5 log copies/ml. We amplified and sequenced the E2 and 5'-untranslated regions from the purified viral RNA from CSF by RT-PCR. Both sequences belong to genotype 3 and there were some minor nucleotide divergence among the E2 sequences from the CSF of the patient. These data suggest that GBV-C may be able to penetrate the blood-brain barrier and colonize the CNS of HIV-infected patients. However, the exact mechanisms and potential effect of the infected GBV-C in CNS on HIV-associated neuropathy needs to be further explored. PMID:26081197

  13. Heterogeneous structures formed by conserved RNA sequences within the HIV reverse transcription initiation site

    PubMed Central

    Coey, Aaron; Larsen, Kevin; Puglisi, Joseph D.; Viani Puglisi, Elisabetta

    2016-01-01

    Reverse transcription is a key process in the early steps of HIV infection. This process initiates within a specific complex formed by the 5′ UTR of the HIV genomic RNA (vRNA) and a host primer tRNALys3. Using nuclear magnetic resonance (NMR) spectroscopy and single-molecule fluorescence spectroscopy, we detect two distinct conformers adopted by the tRNA/vRNA initiation complex. We directly show that an interaction between the conserved 8-nucleotide viral RNA primer activation signal (PAS) and the primer tRNA occurs in one of these conformers. This intermolecular PAS interaction likely induces strain on a vRNA intramolecular helix, which must be broken for reverse transcription to initiate. We propose a mechanism by which this vRNA/tRNA conformer relieves the kinetic block formed by the vRNA intramolecular helix to initiate reverse transcription. PMID:27613581

  14. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5

    SciTech Connect

    Mefford, Megan E.; Kunstman, Kevin; Wolinsky, Steven M.; Gabuzda, Dana

    2015-07-15

    Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120–CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues. - Highlights: • We analyze HIV Env sequences and identify amino acids in beta 3 of the gp120 bridging sheet that enhance macrophage tropism. • These amino acids at positions 197 and 200 are present in brain of some patients with HIV-associated dementia. • D197 results in loss of a glycan near the HIV Env trimer apex, which may increase exposure of V3. • These variants may promote infection of macrophages in the brain by enhancing gp120–CCR5 interactions.

  15. The Los Alamos primer

    SciTech Connect

    Serber, R.

    1992-01-01

    This book contains the 1943 lecture notes of Robert Serber. Serber was a protege of J. Robert Oppenheimer and member of the team that built the first atomic bomb - reveal what the Los Alamos scientists knew, and did not know, about the terrifying weapon they were building.

  16. HIV gp120 H375 Is Unique to HIV-1 Subtype CRF01_AE and Confers Strong Resistance to the Entry Inhibitor BMS-599793, a Candidate Microbicide Drug

    PubMed Central

    Schader, Susan M.; Colby-Germinario, Susan P.; Quashie, Peter K.; Oliveira, Maureen; Ibanescu, Ruxandra-Ilinca; Moisi, Daniela; Mespléde, Thibault

    2012-01-01

    BMS-599793 is a small molecule entry inhibitor that binds to human immunodeficiency virus type 1 (HIV-1) gp120, resulting in the inhibition of CD4-dependent entry into cells. Since BMS-599793 is currently considered a candidate microbicide drug, we evaluated its efficacy against a number of primary patient HIV isolates from different subtypes and circulating recombinant forms (CRFs) and showed that activity varied between ∼3 ρM and 7 μM at 50% effective concentrations (EC50s). Interestingly, CRF01_AE HIV-1 isolates consistently demonstrated natural resistance against this compound. Genotypic analysis of >1,600 sequences (Los Alamos HIV sequence database) indicated that a single amino acid polymorphism in Env, H375, may account for the observed BMS-599793 resistance in CRF01_AE HIV-1. Results of site-directed mutagenesis experiments confirmed this hypothesis, and in silico drug docking simulations identified a drug resistance mechanism at the molecular level. In addition, CRF01_AE viruses were shown to be resistant to multiple broadly neutralizing monoclonal antibodies. Thus, our results not only provide insight into how Env polymorphisms may contribute to entry inhibitor resistance but also may help to elucidate how HIV can evade some broadly neutralizing antibodies. Furthermore, the high frequency of H375 in CRF01_AE HIV-1, and its apparent nonoccurrence in other subtypes, could serve as a means for rapid identification of CRF01_AE infections. PMID:22615295

  17. Sequence specificity of viral end DNA binding by HIV-1 integrase reveals critical regions for protein-DNA interaction.

    PubMed Central

    Esposito, D; Craigie, R

    1998-01-01

    HIV-1 integrase specifically recognizes and cleaves viral end DNA during the initial step of retroviral integration. The protein and DNA determinants of the specificity of viral end DNA binding have not been clearly identified. We have used mutational analysis of the viral end LTR sequence, in vitro selection of optimal viral end sequences, and specific photocrosslinking to identify regions of integrase that interact with specific bases in the LTR termini. The results highlight the involvement of the disordered loop of the integrase core domain, specifically residues Q148 and Y143, in binding to the terminal portion of the viral DNA ends. Additionally, we have identified positions upstream in the LTR termini which interact with the C-terminal domain of integrase, providing evidence for the role of that domain in stabilization of viral DNA binding. Finally, we have located a region centered 12 bases from the viral DNA terminus which appears essential for viral end DNA binding in the presence of magnesium, but not in the presence of manganese, suggesting a differential effect of divalent cations on sequence-specific binding. These results help to define important regions of contact between integrase and viral DNA, and assist in the formulation of a molecular model of this vital interaction. PMID:9755183

  18. Genetic Analysis of HIV-1 Subtypes in Nairobi, Kenya

    PubMed Central

    Khoja, Suhail; Ojwang, Peter; Khan, Saeed; Okinda, Nancy; Harania, Reena; Ali, Syed

    2008-01-01

    Background Genetic analysis of a viral infection helps in following its spread in a given population, in tracking the routes of infection and, where applicable, in vaccine design. Additionally, sequence analysis of the viral genome provides information about patterns of genetic divergence that may have occurred during viral evolution. Objective In this study we have analyzed the subtypes of Human Immunodeficiency Virus -1 (HIV-1) circulating in a diverse sample population of Nairobi, Kenya. Methodology 69 blood samples were collected from a diverse subject population attending the Aga Khan University Hospital in Nairobi, Kenya. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs), and used in a Polymerase Chain Reaction (PCR) to amplify the HIV gag gene. The PCR amplimers were partially sequenced, and alignment and phylogenetic analysis of these sequences was performed using the Los Alamos HIV Database. Results Blood samples from 69 HIV-1 infected subjects from varying ethnic backgrounds were analyzed. Sequence alignment and phylogenetic analysis showed 39 isolates to be subtype A, 13 subtype D, 7 subtype C, 3 subtype AD and CRF01_AE, 2 subtype G and 1 subtype AC and 1 AG. Deeper phylogenetic analysis revealed HIV subtype A sequences to be highly divergent as compared to subtypes D and C. Conclusion Our analysis indicates that HIV-1 subtypes in the Nairobi province of Kenya are dominated by a genetically diverse clade A. Additionally, the prevalence of highly divergent, complex subtypes, intersubtypes, and the recombinant forms indicates viral mixing in Kenyan population, possibly as a result of dual infections. PMID:18784834

  19. Recoding method that removes inhibitory sequences and improves HIV gene expression

    DOEpatents

    Rabadan, Raul; Krasnitz, Michael; Robins, Harlan; Witten, Daniela; Levine, Arnold

    2016-08-23

    The invention relates to inhibitory nucleotide signal sequences or "INS" sequences in the genomes of lentiviruses. In particular the invention relates to the AGG motif present in all viral genomes. The AGG motif may have an inhibitory effect on a virus, for example by reducing the levels of, or maintaining low steady-state levels of, viral RNAs in host cells, and inducing and/or maintaining in viral latency. In one aspect, the invention provides vaccines that contain, or are produced from, viral nucleic acids in which the AGG sequences have been mutated. In another aspect, the invention provides methods and compositions for affecting the function of the AGG motif, and methods for identifying other INS sequences in viral genomes.

  20. Hydrogen Exchange Mass Spectrometry of Related Proteins with Divergent Sequences: A Comparative Study of HIV-1 Nef Allelic Variants

    NASA Astrophysics Data System (ADS)

    Wales, Thomas E.; Poe, Jerrod A.; Emert-Sedlak, Lori; Morgan, Christopher R.; Smithgall, Thomas E.; Engen, John R.

    2016-06-01

    Hydrogen exchange mass spectrometry can be used to compare the conformation and dynamics of proteins that are similar in tertiary structure. If relative deuterium levels are measured, differences in sequence, deuterium forward- and back-exchange, peptide retention time, and protease digestion patterns all complicate the data analysis. We illustrate what can be learned from such data sets by analyzing five variants (Consensus G2E, SF2, NL4-3, ELI, and LTNP4) of the HIV-1 Nef protein, both alone and when bound to the human Hck SH3 domain. Regions with similar sequence could be compared between variants. Although much of the hydrogen exchange features were preserved across the five proteins, the kinetics of Nef binding to Hck SH3 were not the same. These observations may be related to biological function, particularly for ELI Nef where we also observed an impaired ability to downregulate CD4 surface presentation. The data illustrate some of the caveats that must be considered for comparison experiments and provide a framework for investigations of other protein relatives, families, and superfamilies with HX MS.

  1. Gag-Protease Sequence Evolution Following Protease Inhibitor Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa.

    PubMed

    Sutherland, Katherine A; Goodall, Ruth L; McCormick, Adele; Kapaata, Anne; Lyagoba, Fred; Kaleebu, Pontiano; Thiltgen, Geant; Gilks, Charles F; Spyer, Moira; Kityo, Cissy; Pillay, Deenan; Dunn, David; Gupta, Ravindra K

    2015-10-01

    Around 2.5 million HIV-infected individuals failing first-line therapy qualify for boosted protease inhibitor (bPI)-based second-line therapy globally. Major resistance mutations are rarely present at treatment failure in patients receiving bPI and the determinants of failure in these patients remain unknown. There is evidence that Gag can impact PI susceptibility. Here, we have sequenced Gag-Protease before and following failure in 23 patients in the SARA trial infected with subtypes A, C, and D viruses. Before bPI, significant variation in Protease and Gag was observed at positions previously associated with PI exposure and resistance including Gag mutations L449P, S451N, and L453P and Protease K20I and L63P. Following PI failure, previously described mutations in Protease and Gag were observed, including those at the cleavage sites such as R361K and P453L. However, the emergence of clear genetic determinants of therapy failure across patients was not observed. Larger Gag sequence datasets will be required to comprehensively identify mutational correlates of bPI failure across subtypes. PMID:26258548

  2. Sequence Analysis of In Vivo-Expressed HIV-1 Spliced RNAs Reveals the Usage of New and Unusual Splice Sites by Viruses of Different Subtypes

    PubMed Central

    Vega, Yolanda; Delgado, Elena; de la Barrera, Jorge; Carrera, Cristina; Zaballos, Ángel; Cuesta, Isabel; Mariño, Ana; Ocampo, Antonio; Miralles, Celia; Pérez-Castro, Sonia; Álvarez, Hortensia; López-Miragaya, Isabel; García-Bodas, Elena; Díez-Fuertes, Francisco; Thomson, Michael M.

    2016-01-01

    HIV-1 RNAs are generated through a complex splicing mechanism, resulting in a great diversity of transcripts, which are classified in three major categories: unspliced, singly spliced (SS), and doubly spliced (DS). Knowledge on HIV-1 RNA splicing in vivo and by non-subtype B viruses is scarce. Here we analyze HIV-1 RNA splice site usage in CD4+CD25+ lymphocytes from HIV-1-infected individuals through pyrosequencing. HIV-1 DS and SS RNAs were amplified by RT-PCR in 19 and 12 samples, respectively. 13,108 sequences from HIV-1 spliced RNAs, derived from viruses of five subtypes (A, B, C, F, G), were identified. In four samples, three of non-B subtypes, five 3’ splice sites (3’ss) mapping to unreported positions in the HIV-1 genome were identified. Two, designated A4i and A4j, were used in 22% and 25% of rev RNAs in two viruses of subtypes B and A, respectively. Given their close proximity (one or two nucleotides) to A4c and A4d, respectively, they could be viewed as variants of these sites. Three 3’ss, designated A7g, A7h, and A7i, located 20, 32, and 18 nucleotides downstream of A7, respectively, were identified in a subtype C (A7g, A7h) and a subtype G (A7i) viruses, each in around 2% of nef RNAs. The new splice sites or variants of splice sites were associated with the usual sequence features of 3’ss. Usage of unusual 3’ss A4d, A4e, A5a, A7a, and A7b was also detected. A4f, previously identified in two subtype C viruses, was preferentially used by rev RNAs of a subtype C virus. These results highlight the great diversity of in vivo splice site usage by HIV-1 RNAs. The fact that four of five newly identified splice sites or variants of splice sites were detected in non-subtype B viruses allows anticipating an even greater diversity of HIV-1 splice site usage than currently known. PMID:27355361

  3. A Short Sequence Motif in the 5′ Leader of the HIV-1 Genome Modulates Extended RNA Dimer Formation and Virus Replication*

    PubMed Central

    van Bel, Nikki; Das, Atze T.; Cornelissen, Marion; Abbink, Truus E. M.; Berkhout, Ben

    2014-01-01

    The 5′ leader of the HIV-1 RNA genome encodes signals that control various steps in the replication cycle, including the dimerization initiation signal (DIS) that triggers RNA dimerization. The DIS folds a hairpin structure with a palindromic sequence in the loop that allows RNA dimerization via intermolecular kissing loop (KL) base pairing. The KL dimer can be stabilized by including the DIS stem nucleotides in the intermolecular base pairing, forming an extended dimer (ED). The role of the ED RNA dimer in HIV-1 replication has hardly been addressed because of technical challenges. We analyzed a set of leader mutants with a stabilized DIS hairpin for in vitro RNA dimerization and virus replication in T cells. In agreement with previous observations, DIS hairpin stability modulated KL and ED dimerization. An unexpected previous finding was that mutation of three nucleotides immediately upstream of the DIS hairpin significantly reduced in vitro ED formation. In this study, we tested such mutants in vivo for the importance of the ED in HIV-1 biology. Mutants with a stabilized DIS hairpin replicated less efficiently than WT HIV-1. This defect was most severe when the upstream sequence motif was altered. Virus evolution experiments with the defective mutants yielded fast replicating HIV-1 variants with second site mutations that (partially) restored the WT hairpin stability. Characterization of the mutant and revertant RNA molecules and the corresponding viruses confirmed the correlation between in vitro ED RNA dimer formation and efficient virus replication, thus indicating that the ED structure is important for HIV-1 replication. PMID:25368321

  4. Comparison of HIV type 1 sequences from plasma, cell-free breast milk, and cell-associated breast milk viral populations in treated and untreated women in Mozambique.

    PubMed

    Andreotti, Mauro; Galluzzo, Clementina M; Guidotti, Giovanni; Germano, Paola; Altan, Annamaria Doro; Pirillo, Maria Franca; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Giuliano, Marina

    2009-07-01

    We analyzed the sequences of the HIV viral populations obtained from plasma, cell-free breast milk, and breast milk cells of HAART-treated (23) and untreated (30) HIV-infected women to obtain information about the origin of the breast milk virus. Sequence analyses of viruses were performed using the TruGene HIV-1 assay. Direct sequences of the reverse transcriptase (RT) and protease (PR) genes were analyzed using the Phylip 3.68 suite of sequence analysis program and pairwise evolutionary distances were calculated with the Kimura two parameter model for estimation of distances. We found that the genetic distances between the plasma and the cell-free breast milk viruses and between the cell-free and cell-associated breast milk viruses for RT were higher in HAART-receiving women than in untreated women, suggesting viral evolution under selective drug pressure in breast milk. Our data support the hypothesis of the presence of an actively replicating viral population in the breast milk compartment, distinct from that present in plasma. PMID:19552594

  5. Sequencing and Phylogenetic Analysis of Near Full-Length HIV-1 Subtypes A, B, G and Unique Recombinant AC and AD Viral Strains Identified in South Africa

    PubMed Central

    Wilkinson, Eduan; Holzmayer, Vera; Jacobs, Graeme B.; de Oliveira, Tulio; Brennan, Catherine A.; Hackett, John; van Rensburg, Estrelita Janse

    2015-01-01

    Abstract By the end of 2012, more than 6.1 million people were infected with HIV-1 in South Africa. Subtype C was responsible for the majority of these infections and more than 300 near full-length genomes (NFLGs) have been published. Currently very few non-subtype C isolates have been identified and characterized within the country, particularly full genome non-C isolates. Seven patients from the Tygerberg Virology (TV) cohort were previously identified as possible non-C subtypes and were selected for further analyses. RNA was isolated from five individuals (TV047, TV096, TV101, TV218, and TV546) and DNA from TV016 and TV1057. The NFLGs of these samples were amplified in overlapping fragments and sequenced. Online subtyping tools REGA version 3 and jpHMM were used to screen for subtypes and recombinants. Maximum likelihood (ML) phylogenetic analysis (phyML) was used to infer subtypes and SimPlot was used to confirm possible intersubtype recombinants. We identified three subtype B (TV016, TV047, and TV1057) isolates, one subtype A1 (TV096), one subtype G (TV546), one unique AD (TV101), and one unique AC (TV218) recombinant form. This is the first NFLG of subtype G that has been described in South Africa. The subtype B sequences described also increased the NFLG subtype B sequences in Africa from three to six. There is a need for more NFLG sequences, as partial HIV-1 sequences may underrepresent viral recombinant forms. It is also necessary to continue monitoring the evolution and spread of HIV-1 in South Africa, because understanding viral diversity may play an important role in HIV-1 prevention strategies. PMID:25492033

  6. Comparison of SIV and HIV-1 genomic RNA structures reveals impact of sequence evolution on conserved and non-conserved structural motifs.

    PubMed

    Pollom, Elizabeth; Dang, Kristen K; Potter, E Lake; Gorelick, Robert J; Burch, Christina L; Weeks, Kevin M; Swanstrom, Ronald

    2013-01-01

    RNA secondary structure plays a central role in the replication and metabolism of all RNA viruses, including retroviruses like HIV-1. However, structures with known function represent only a fraction of the secondary structure reported for HIV-1(NL4-3). One tool to assess the importance of RNA structures is to examine their conservation over evolutionary time. To this end, we used SHAPE to model the secondary structure of a second primate lentiviral genome, SIVmac239, which shares only 50% sequence identity at the nucleotide level with HIV-1NL4-3. Only about half of the paired nucleotides are paired in both genomic RNAs and, across the genome, just 71 base pairs form with the same pairing partner in both genomes. On average the RNA secondary structure is thus evolving at a much faster rate than the sequence. Structure at the Gag-Pro-Pol frameshift site is maintained but in a significantly altered form, while the impact of selection for maintaining a protein binding interaction can be seen in the conservation of pairing partners in the small RRE stems where Rev binds. Structures that are conserved between SIVmac239 and HIV-1(NL4-3) also occur at the 5' polyadenylation sequence, in the plus strand primer sites, PPT and cPPT, and in the stem-loop structure that includes the first splice acceptor site. The two genomes are adenosine-rich and cytidine-poor. The structured regions are enriched in guanosines, while unpaired regions are enriched in adenosines, and functionaly important structures have stronger base pairing than nonconserved structures. We conclude that much of the secondary structure is the result of fortuitous pairing in a metastable state that reforms during sequence evolution. However, secondary structure elements with important function are stabilized by higher guanosine content that allows regions of structure to persist as sequence evolution proceeds, and, within the confines of selective pressure, allows structures to evolve. PMID:23593004

  7. Sequencing and phylogenetic analysis of near full-length HIV-1 subtypes A, B, G and unique recombinant AC and AD viral strains identified in South Africa.

    PubMed

    Wilkinson, Eduan; Holzmayer, Vera; Jacobs, Graeme B; de Oliveira, Tulio; Brennan, Catherine A; Hackett, John; van Rensburg, Estrelita Janse; Engelbrecht, Susan

    2015-04-01

    By the end of 2012, more than 6.1 million people were infected with HIV-1 in South Africa. Subtype C was responsible for the majority of these infections and more than 300 near full-length genomes (NFLGs) have been published. Currently very few non-subtype C isolates have been identified and characterized within the country, particularly full genome non-C isolates. Seven patients from the Tygerberg Virology (TV) cohort were previously identified as possible non-C subtypes and were selected for further analyses. RNA was isolated from five individuals (TV047, TV096, TV101, TV218, and TV546) and DNA from TV016 and TV1057. The NFLGs of these samples were amplified in overlapping fragments and sequenced. Online subtyping tools REGA version 3 and jpHMM were used to screen for subtypes and recombinants. Maximum likelihood (ML) phylogenetic analysis (phyML) was used to infer subtypes and SimPlot was used to confirm possible intersubtype recombinants. We identified three subtype B (TV016, TV047, and TV1057) isolates, one subtype A1 (TV096), one subtype G (TV546), one unique AD (TV101), and one unique AC (TV218) recombinant form. This is the first NFLG of subtype G that has been described in South Africa. The subtype B sequences described also increased the NFLG subtype B sequences in Africa from three to six. There is a need for more NFLG sequences, as partial HIV-1 sequences may underrepresent viral recombinant forms. It is also necessary to continue monitoring the evolution and spread of HIV-1 in South Africa, because understanding viral diversity may play an important role in HIV-1 prevention strategies.

  8. Antiretroviral treatment sequencing strategies to overcome HIV type 1 drug resistance in adolescents and adults in low-middle-income countries.

    PubMed

    De Luca, Andrea; Hamers, Raphael L; Schapiro, Jonathan M

    2013-06-15

    Antiretroviral treatment (ART) is expanding to human immunodeficiency virus type 1 (HIV-1)-infected persons in low-middle income countries, thanks to a public health approach. With 3 available drug classes, 2 ART sequencing lines are programmatically foreseen. The emergence and transmission of viral drug resistance represents a challenge to the efficacy of ART. Knowledge of HIV-1 drug resistance selection associated with specific drugs and regimens and the consequent activity of residual drug options are essential in programming ART sequencing options aimed at preserving ART efficacy for as long as possible. This article determines optimal ART sequencing options for overcoming HIV-1 drug resistance in resource-limited settings, using currently available drugs and treatment monitoring opportunities. From the perspective of drug resistance and on the basis of limited virologic monitoring data, optimal sequencing seems to involve use of a tenofovir-containing nonnucleoside reverse-transcriptase inhibitor-based first-line regimen, followed by a zidovudine-containing, protease inhibitor (PI)-based second-line regimen. Other options and their consequences are explored by considering within-class and between-class sequencing opportunities, including boosted PI monotherapies and future options with integrase inhibitors. Nucleoside reverse-transcriptase inhibitor resistance pathways in HIV-1 subtype C suggest an additional reason for accelerating stavudine phase out. Viral load monitoring avoids the accumulation of resistance mutations that significantly reduce the activity of next-line options. Rational use of resources, including broader access to viral load monitoring, will help ensure 3 lines of fully active treatment options, thereby increasing the duration of ART success. PMID:23687291

  9. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5.

    PubMed

    Mefford, Megan E; Kunstman, Kevin; Wolinsky, Steven M; Gabuzda, Dana

    2015-07-01

    Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120-CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues.

  10. Bioinformatic analysis of neurotropic HIV envelope sequences identifies polymorphisms in the gp120 bridging sheet that increase macrophage-tropism through enhanced interactions with CCR5.

    PubMed

    Mefford, Megan E; Kunstman, Kevin; Wolinsky, Steven M; Gabuzda, Dana

    2015-07-01

    Macrophages express low levels of the CD4 receptor compared to T-cells. Macrophage-tropic HIV strains replicating in brain of untreated patients with HIV-associated dementia (HAD) express Envs that are adapted to overcome this restriction through mechanisms that are poorly understood. Here, bioinformatic analysis of env sequence datasets together with functional studies identified polymorphisms in the β3 strand of the HIV gp120 bridging sheet that increase M-tropism. D197, which results in loss of an N-glycan located near the HIV Env trimer apex, was detected in brain in some HAD patients, while position 200 was estimated to be under positive selection. D197 and T/V200 increased fusion and infection of cells expressing low CD4 by enhancing gp120 binding to CCR5. These results identify polymorphisms in the HIV gp120 bridging sheet that overcome the restriction to macrophage infection imposed by low CD4 through enhanced gp120-CCR5 interactions, thereby promoting infection of brain and other macrophage-rich tissues. PMID:25797607

  11. Association between a naturally arising polymorphism within a functional region of HIV-1 Nef and disease progression in chronic HIV-1 infection.

    PubMed

    Meribe, Stanley C; Hasan, Zafrul; Mahiti, Macdonald; Mwimanzi, Francis; Toyoda, Mako; Mori, Masahiko; Gatanaga, Hiroyuki; Kikuchi, Tadashi; Miura, Toshiyuki; Kawana-Tachikawa, Ai; Iwamoto, Aikichi; Oka, Shinichi; Ueno, Takamasa

    2015-08-01

    HIV-1 Nef mediates downregulation of HLA class I (HLA-I) through a number of highly conserved sequence motifs. We investigated the in vivo implication(s) of naturally arising polymorphisms in functional motifs in HIV-1 Nef that are associated with HLA-I downregulation, including the acidic cluster, polyproline, di-arginine and Met-20 regions. Plasma samples from treatment-naive, chronically HIV-1 infected subjects were collected after obtaining informed consent, and viral RNA was extracted and amplified by nested RT-PCR. The resultant nef amplicons were sequenced directly, and subtype-B sequences with an intact open reading frame (n = 406) were included in our analyses. There was over-representation of isoleucine at position 20 (Ile-20) in our dataset when compared to sequences in the Los Alamos sequence database (17.7 vs. 6.9 %, p = 0.0309). The presence of having Ile-20 in Nef was found to be associated with higher median plasma viral load (p = 0.013), independent of associated codons or viral lineage effects, whereas no clinical association was found with polymorphisms in the other functional motifs. Moreover, introduction of a Met-20-to-Ile mutation in a laboratory strain SF2 Nef resulted in a modest, albeit not statistically significant, increase in HLA class I downregulation activity (p = 0.06). Taken together, we have identified a naturally arising polymorphism, Ile-20, within HIV-1 subtype B Nef that is associated with poorer disease outcome.

  12. Los Alamos National Laboratory

    SciTech Connect

    Dogliani, Harold O

    2011-01-19

    The purpose of the briefing is to describe general laboratory technical capabilities to be used for various groups such as military cadets or university faculty/students and post docs to recruit into a variety of Los Alamos programs. Discussed are: (1) development and application of high leverage science to enable effeictive, predictable and reliability outcomes; (2) deter, detect, characterize, reverse and prevent the proliferation of weapons of mass destruction and their use by adversaries and terrorists; (3) modeling and simulation to define complex processes, predict outcomes, and develop effective prevention, response, and remediation strategies; (4) energetic materials and hydrodynamic testing to develop materials for precise delivery of focused energy; (5) materials cience focused on fundamental understanding of materials behaviors, their quantum-molecular properties, and their dynamic responses, and (6) bio-science to rapidly detect and characterize pathogens, to develop vaccines and prophylactic remedies, and to develop attribution forensics.

  13. Assessment of Immunologically Relevant Dynamic Tertiary Structural Features of the HIV-1 V3 Loop Crown R2 Sequence by ab initio Folding

    PubMed Central

    Almond, David; Cardozo, Timothy

    2010-01-01

    The antigenic diversity of HIV-1 has long been an obstacle to vaccine design, and this variability is especially pronounced in the V3 loop of the virus' surface envelope glycoprotein. We previously proposed that the crown of the V3 loop, although dynamic and sequence variable, is constrained throughout the population of HIV-1 viruses to an immunologically relevant β-hairpin tertiary structure. Importantly, there are thousands of different V3 loop crown sequences in circulating HIV-1 viruses, making 3D structural characterization of trends across the diversity of viruses difficult or impossible by crystallography or NMR. Our previous successful studies with folding of the V3 crown1, 2 used the ab initio algorithm 3 accessible in the ICM-Pro molecular modeling software package (Molsoft LLC, La Jolla, CA) and suggested that the crown of the V3 loop, specifically from positions 10 to 22, benefits sufficiently from the flexibility and length of its flanking stems to behave to a large degree as if it were an unconstrained peptide freely folding in solution. As such, rapid ab initio folding of just this portion of the V3 loop of any individual strain of the 60,000+ circulating HIV-1 strains can be informative. Here, we folded the V3 loop of the R2 strain to gain insight into the structural basis of its unique properties. R2 bears a rare V3 loop sequence thought to be responsible for the exquisite sensitivity of this strain to neutralization by patient sera and monoclonal antibodies4, 5. The strain mediates CD4-independent infection and appears to elicit broadly neutralizing antibodies. We demonstrate how evaluation of the results of the folding can be informative for associating observed structures in the folding with the immunological activities observed for R2. PMID:20864931

  14. Deep sequencing and Circos analyses of antibody libraries reveal antigen-driven selection of Ig VH genes during HIV-1 infection.

    PubMed

    Xiao, Madelyne; Prabakaran, Ponraj; Chen, Weizao; Kessing, Bailey; Dimitrov, Dimiter S

    2013-12-01

    The vast diversity of antibody repertoires is largely attributed to heavy chain (V(H)) recombination of variable (V), diversity (D) and joining (J) gene segments. We used 454 sequencing information of the variable domains of the antibody heavy chain repertoires from neonates, normal adults and an HIV-1-infected individual, to analyze, with Circos software, the VDJ pairing patterns at birth, adulthood and a time-dependent response to HIV-1 infection. Our comparative analyses of the Ig VDJ repertoires from these libraries indicated that, from birth to adulthood, VDJ recombination patterns remain the same with some slight changes, whereas some V(H) families are selected and preferentially expressed after long-term infection with HIV-1. We also demonstrated that the immune system responds to HIV-1 chronic infection by selectively expanding certain HV families in an attempt to combat infection. Our findings may have implications for understanding immune responses in pathology as well as for development of new therapeutics and vaccines.

  15. Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals

    PubMed Central

    Pickering, Suzanne; Hué, Stephane; Kim, Eun-Young; Reddy, Susheel; Wolinsky, Steven M.; Neil, Stuart J. D.

    2014-01-01

    The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires throughout infection in 14 individuals infected with HIV-1 clade B revealed extensive amino acid diversity of the Vpu protein. For the most part, this variation in Vpu increases over the course of infection and is associated with predicted epitopes of the individual's MHC class I haplotype, suggesting CD8+ T cell pressure is the major driver of Vpu sequence diversity within the host. Despite this variability, the Vpu functions of targeting CD4 and counteracting both physical virus restriction and NF-κB activation by tetherin are rigorously maintained throughout HIV-1 infection. Only a minority of circulating alleles bear lesions in either of these activities at any given time, suggesting functional Vpu mutants are heavily selected against even at later stages of infection. Comparison of Vpu proteins defective for one or several functions reveals novel determinants of CD4 downregulation, counteraction of tetherin restriction, and inhibition of NF-κB signalling. These data affirm the importance of Vpu functions for in vivo persistence of HIV-1 within infected individuals, not simply for transmission, and highlight its potential as a target for antiviral therapy. PMID:24465210

  16. The role of recombination in the emergence of a complex and dynamic HIV epidemic

    PubMed Central

    2010-01-01

    Background Inter-subtype recombinants dominate the HIV epidemics in three geographical regions. To better understand the role of HIV recombinants in shaping the current HIV epidemic, we here present the results of a large-scale subtyping analysis of 9435 HIV-1 sequences that involve subtypes A, B, C, G, F and the epidemiologically important recombinants derived from three continents. Results The circulating recombinant form CRF02_AG, common in West Central Africa, appears to result from recombination events that occurred early in the divergence between subtypes A and G, followed by additional recent recombination events that contribute to the breakpoint pattern defining the current recombinant lineage. This finding also corrects a recent claim that G is a recombinant and a descendant of CRF02, which was suggested to be a pure subtype. The BC and BF recombinants in China and South America, respectively, are derived from recent recombination between contemporary parental lineages. Shared breakpoints in South America BF recombinants indicate that the HIV-1 epidemics in Argentina and Brazil are not independent. Therefore, the contemporary HIV-1 epidemic has recombinant lineages of both ancient and more recent origins. Conclusions Taken together, we show that these recombinant lineages, which are highly prevalent in the current HIV epidemic, are a mixture of ancient and recent recombination. The HIV pandemic is moving towards having increasing complexity and higher prevalence of recombinant forms, sometimes existing as "families" of related forms. We find that the classification of some CRF designations need to be revised as a consequence of (1) an estimated > 5% error in the original subtype assignments deposited in the Los Alamos sequence database; (2) an increasing number of CRFs are defined while they do not readily fit into groupings for molecular epidemiology and vaccine design; and (3) a dynamic HIV epidemic context. PMID:20331894

  17. Unbiased proteomic analysis of proteins interacting with the HIV-1 5′LTR sequence: role of the transcription factor Meis

    PubMed Central

    Tacheny, A.; Michel, S.; Dieu, M.; Payen, L.; Arnould, T.; Renard, P.

    2012-01-01

    To depict the largest picture of a core promoter interactome, we developed a one-step DNA-affinity capture method coupled with an improved mass spectrometry analysis process focused on the identification of low abundance proteins. As a proof of concept, this method was developed through the analysis of 230 bp contained in the 5′long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1). Beside many expected interactions, many new transcriptional regulators were identified, either transcription factors (TFs) or co-regulators, which interact directly or indirectly with the HIV-1 5′LTR. Among them, the homeodomain-containing TF myeloid ectopic viral integration site was confirmed to functionally interact with a specific binding site in the HIV-1 5′LTR and to act as a transcriptional repressor, probably through recruitment of the repressive Sin3A complex. This powerful and validated DNA-affinity approach could also be used as an efficient screening tool to identify a large set of proteins that physically interact, directly or indirectly, with a DNA sequence of interest. Combined with an in silico analysis of the DNA sequence of interest, this approach provides a powerful approach to select the interacting candidates to validate functionally by classical approaches. PMID:22904091

  18. ASC platforms at Los Alamos.

    SciTech Connect

    Shaw, S. R.

    2004-01-01

    This talk describes the history, current state, and future plans for ASC computational and data storage service at Los Alamos. The of the systems and services described is limited to those installed in and managed by Group CCN-7.

  19. [Production and evaluation of immunologic characteristics of mzNLA-3, a non-infectious HIV-1 clone with a large deletion in the pol sequence].

    PubMed

    Aghasadeghi, M R; Zabihollahi, R; Sadat, S M; Salehi, M; Ashtiani, S H; Namazi, R; Kashanizadeh, N; Azadmanesh, K

    2013-01-01

    Inactivation ofintegrase and reverse transcriptase can revoke the replication of HIV virions, and non-infectious HIV particles are desirable virus-like particle (VLP) vaccine candidates. Here, we produced inactive in replication HIV-1 particles fit for vaccine and virological purposes by introducing a mutation into the pol sequence. Proviral DNA (pNLA-3) was cut at two points in the pol region using the Bal I restriction enzyme and then religated. HEK 293T cells were transfected with the resultant plasmid (pmzNL4-3) to produce mutated virions. To confirm a production of VLPs and evaluate their biological activity the p24 load and syncytium formation (MT2 cells) were analyzed. The assay indicated that mzNL4-3 virions were assembled and contained functional envelope glycoproteins (ENV). In addition, mzNL4-3 virions were not able to infect MT2 and HEK 293T cells. Furthermore, the immunogenicity of VLPs was investigated in a mouse model. According to the data on vaccinated mice, the titer of ENV-specific antibodies rose rapidly after a boosting injection. Moreover, lymphoid cells extracted from these mice proliferated after exposure to the antigen. The mzNL4-3 virus particles possessed immunogenic antigens of HIV and can effectively trigger humoral and CD4 immune responses. Non-infectious mzNL4-3 virions may also be used in biomedical experiments to improve the biological safety conditions. Moreover, the mzNL4-3 seems to be a promising candidate for further HIV-1 vaccine investigations. PMID:23808159

  20. Genetic Attributes of Blood-Derived Subtype-C HIV-1 tat and env in India and Neurocognitive Function

    PubMed Central

    Tilghman, Myres W.; Bhattacharya, Jayanta; Deshpande, Suprit; Ghate, Manisha; Espitia, Stephen; Grant, Igor; Marcotte, Thomas D.; Smith, Davey; Mehendale, Sanjay

    2013-01-01

    Genetic elements in HIV-1 subtype B tat and env are associated with neurotoxicity yet less is known about other subtypes. HIV-1 sub-type C tat and env sequences were analyzed to determine viral genetic elements associated with neurocognitive impairment in a large Indian cohort. Population-based sequences of HIV-1 tat (exon 1) and env (C2-V3 coding region) were generated from blood plasma of HIV-infected patients in Pune, India. Participants were classified as cognitively normal or impaired based on neuropsychological assessment. Tests for signature residues, positive and negative selection, entropy, and ambiguous bases were performed using tools available through Los Alamos National Laboratory (http://www.hiv.lanl.gov) and Datamonkey (http://www.datamonkey.org). HIV-1 subtype C tat and env sequences were analyzed for 155 and 160 participants, of which 34–36% were impaired. Two signature residues were unique to impaired participants in exon 1 of tat at codons 29 (arginine) and 68 (proline). Positive selection was noted at codon 29 among normal participants and at codon 68 in both groups. The signature at codon 29 was also a signature for low CD4+ (<200 cells/mm3) counts but remained associated with impairment after exclusion of those with low CD4+ counts. No unique genetic signatures were noted in env. In conclusion, two signature residues were identified in exon 1 of HIV-1 subtype C tat that were associated with neurocognitive impairment in India and not completely accounted for by HIV disease progression. These signatures support a linkage between diversifying selection in HIV-1 subtype C tat and neurocognitive impairment. PMID:24150902

  1. Minimization of genetic distances by the consensus, ancestral, and center-of-tree (COT) sequences for HIV-1 variants within an infected individual and the design of reagents to test immune reactivity.

    PubMed

    Kesturu, Girish S; Colleton, Bonnie A; Liu, Yi; Heath, Laura; Shaikh, Obaid Shakil; Rinaldo, Charles R; Shankarappa, Raj

    2006-05-10

    Eliciting maximal immune responses to highly divergent viruses is a challenge and a focus in AIDS vaccine development. Another challenge is to identify the immune correlates of protective immunity. Recent AIDS vaccine design approaches attempt to use reconstructed centralized viral sequences that minimize genetic differences to circulating viruses. Using these approaches, we derive and analyze consensus (CON), ancestral (ANC), and center-of-tree (COT) sequences to represent intra-individual HIV-1 env variants encoding a range of diversities and phylogenetic structures. Each reconstructed sequence significantly minimized genetic distances to extant sequences throughout the first 5 years of infection of an individual. Interestingly, ANC sequences diverged and were not significantly better than extant sequences in minimizing genetic distances at later stages of infection and disease, likely due to the development of a substantially asymmetric phylogeny. COT or CON sequences derived from autologous virus samplings may be useful for increasing the sensitivity of assessments of immune reactivity against HIV.

  2. Ultra-Deep Sequencing of HIV-1 near Full-Length and Partial Proviral Genomes Reveals High Genetic Diversity among Brazilian Blood Donors

    PubMed Central

    Pessôa, Rodrigo; Loureiro, Paula; Esther Lopes, Maria; Carneiro-Proietti, Anna B. F.; Sabino, Ester C; Busch, Michael P.; Sanabani, Sabri S

    2016-01-01

    Background Here, we aimed to gain a comprehensive picture of the HIV-1 diversity in the northeast and southeast part of Brazil. To this end, a high-throughput sequencing-by-synthesis protocol and instrument were used to characterize the near full length (NFLG) and partial HIV-1 proviral genome in 259 HIV-1 infected blood donors at four major blood centers in Brazil: Pro-Sangue foundation (São Paulo state (SP), n 51), Hemominas foundation (Minas Gerais state (MG), n 41), Hemope foundation (Recife state (PE), n 96) and Hemorio blood bank (Rio de Janeiro (RJ), n 70). Materials and Methods A total of 259 blood samples were obtained from 195 donors with long-standing infections and 64 donors with a lack of stage information. DNA was extracted from the peripheral blood mononuclear cells (PBMCs) to amplify the HIV-1 NFLGs from five overlapping fragments. The amplicons were molecularly bar-coded, pooled, and sequenced by Illumina paired-end protocol. Results Of the 259 samples studied, 208 (80%) NFLGs and 49 (18.8%) partial fragments were de novo assembled into contiguous sequences and successfully subtyped. Of these 257 samples, 183 (71.2%) were pure subtypes consisting of clade B (n = 167, 65%), C (n = 10, 3.9%), F1 (n = 4, 1.5%), and D (n = 2, 0.7%). Recombinant viruses were detected in 74 (28.8%) samples and consist of unique BF1 (n = 41, 15.9%), BC (n = 7, 2.7%), BCF1 (n = 4, 1.5%), CF1 and CDK (n = 1, 0.4%, each), CRF70_BF1 (n = 4, 1.5%), CRF71_BF1 (n = 12, 4.7%), and CRF72_BF1 (n = 4, 1.5%). Evidence of dual infection was detected in four patients coinfected with the same subtype (n = 3) and distinct subtype (n = 1). Conclusion Based on this work, subtype B appears to be the prevalent subtype followed by a high proportion of intersubtype recombinants that appeared to be arising continually in this country. Our study represents the largest analysis of the viral NFLG ever undertaken worldwide and provides insights into the understanding the genesis of the HIV-1

  3. Microbiome in HIV infection

    PubMed Central

    Salas, January T.; Chang, Theresa L.

    2014-01-01

    HIV primary infection occurs at mucosa tissues, suggesting an intricate interplay between microbiome and HIV infection. Recent advanced technologies of high-throughput sequencing and bioinformatics allow researchers to explore nonculturable microbes including bacteria, virus and fungi and their association with diseases. HIV/SIV infection is associated with microbiome shifts and immune activation that may affect the outcome of disease progression. Similarly, altered microbiome and inflammation are associated with increased risks of HIV acquisition, suggesting the role of microbiome in HIV transmission. In this review, we will focus on microbiome in HIV infection at various mucosal compartments. Understanding the relationship between microbiome and HIV may offer insights into development of better strategies for HIV prevention and treatment. PMID:25439273

  4. Increased breadth and depth of cytotoxic T lymphocytes responses against HIV-1-B Nef by inclusion of epitope variant sequences.

    PubMed

    Rolland, Morgane; Frahm, Nicole; Nickle, David C; Jojic, Nebojsa; Deng, Wenjie; Allen, Todd M; Brander, Christian; Heckerman, David E; Mullins, James I

    2011-03-28

    Different vaccine approaches cope with HIV-1 diversity, ranging from centralized(1-4) to variability-encompassing(5-7) antigens. For all these strategies, a concern remains: how does HIV-1 diversity impact epitope recognition by the immune system? We studied the relationship between HIV-1 diversity and CD8(+) T Lymphocytes (CTL) targeting of HIV-1 subtype B Nef using 944 peptides (10-mers overlapping by nine amino acids (AA)) that corresponded to consensus peptides and their most common variants in the HIV-1-B virus population. IFN-γ ELISpot assays were performed using freshly isolated PBMC from 26 HIV-1-infected persons. Three hundred and fifty peptides elicited a response in at least one individual. Individuals targeted a median of 7 discrete regions. Overall, 33% of responses were directed against viral variants but not elicited against consensus-based test peptides. However, there was no significant relationship between the frequency of a 10-mer in the viral population and either its frequency of recognition (Spearman's correlation coefficient ρ = 0.24) or the magnitude of the responses (ρ = 0.16). We found that peptides with a single mutation compared to the consensus were likely to be recognized (especially if the change was conservative) and to elicit responses of similar magnitude as the consensus peptide. Our results indicate that cross-reactivity between rare and frequent variants is likely to play a role in the expansion of CTL responses, and that maximizing antigenic diversity in a vaccine may increase the breadth and depth of CTL responses. However, since there are few obvious preferred pathways to virologic escape, the diversity that may be required to block all potential escape pathways may be too large for a realistic vaccine to accommodate. Furthermore, since peptides were not recognized based on their frequency in the population, it remains unclear by which mechanisms variability-inclusive antigens (i.e., constructs enriched with frequent

  5. Concordance of HIV Type 1 Tropism Phenotype to Predictions Using Web-Based Analysis of V3 Sequences: Composite Algorithms May Be Needed to Properly Assess Viral Tropism

    PubMed Central

    Cabral, Gabriela Bastos; Ferreira, João Leandro de Paula; Coelho, Luana Portes Osório; Fonsi, Mylva; Estevam, Denise Lotufo; Cavalcanti, Jaqueline Souza

    2012-01-01

    Abstract Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications. PMID:21919801

  6. Concordance of HIV type 1 tropism phenotype to predictions using web-based analysis of V3 sequences: composite algorithms may be needed to properly assess viral tropism.

    PubMed

    Cabral, Gabriela Bastos; Ferreira, João Leandro de Paula; Coelho, Luana Portes Osório; Fonsi, Mylva; Estevam, Denise Lotufo; Cavalcanti, Jaqueline Souza; Brígido, Luis Fernando de Macedo

    2012-07-01

    Genotypic prediction of HIV-1 tropism has been considered a practical surrogate for phenotypic tests and recently an European Consensus has set up recommendations for its use in clinical practice. Twenty-five antiretroviral-experienced patients, all heavily treated cases with a median of 16 years of antiretroviral therapy, had viral tropism determined by the Trofile assay and predicted by HIV-1 sequencing of partial env, followed by interpretation using web-based tools. Trofile determined 17/24 (71%) as X4 tropic or dual/mixed viruses, with one nonreportable result. The use of European consensus recommendations for single sequences (geno2pheno false-positive rates 20% cutoff) would lead to 4/24 (16.7%) misclassifications, whereas a composite algorithm misclassified 1/24 (4%). The use of the geno2pheno clinical option using CD4 T cell counts at collection was useful in resolving some discrepancies. Applying the European recommendations followed by additional web-based tools for cases around the recommended cutoff would resolve most misclassifications.

  7. Prokaryotic ribosomes recode the HIV-1 gag-pol-1 frameshift sequence by an E/P site post-translocation simultaneous slippage mechanism.

    PubMed Central

    Horsfield, J A; Wilson, D N; Mannering, S A; Adamski, F M; Tate, W P

    1995-01-01

    The mechanism favoured for -1 frameshifting at typical retroviral sites is a pre-translocation simultaneous slippage model. An alternative post-translocation mechanism would also generate the same protein sequence across the frameshift site and therefore in this study the strategic placement of a stop codon has been used to distinguish between the two mechanisms. A 26 base pair frameshift sequence from the HIV-1 gag-pol overlap has been modified to include a stop codon immediately 3' to the heptanucleotide frameshift signal, where it often occurs naturally in retroviral recoding sites. Stop codons at the 3'-end of the heptanucleotide sequence decreased the frame-shifting efficiency on prokaryote ribosomes and the recording event was further depressed when the levels of the release factors in vivo were increased. In the presence of elevated levels of a defective release factor 2, frameshifting efficiency in vivo was increased in the constructs containing the stop codons recognized specifically by that release factor. These results are consistent with the last six nucleotides of the heptanucleotide slippery sequence occupying the ribosomal E and P sites, rather than the P and A sites, with the next codon occupying the A site and therefore with a post-translocation rather than a pre-translocation -1 slippage model. Images PMID:7784201

  8. Short Communication: HIV-1 Subtype B in the Dominican Republic: Evolution and Molecular Epidemiology.

    PubMed

    López, Pablo; Rivera-Amill, Vanessa; Paulino-Ramirez, Robert; Yamamura, Yasuhiro

    2015-07-01

    The Caribbean region has the world second highest incidence rate of acquired immunodeficiency syndrome. The island of Hispaniola is composed of two sovereign nations: the Dominican Republic and Haiti. Together, they account for more than 85% of HIV/AIDS cases in the Caribbean; and the Dominican Republic alone has approximately 46,000 (33,000-59,000) HIV-1-infected adults and children. Despite this, the magnitude of the genetic variability and evolution of the HIV-1 virus in the Dominican Republic is unclear. In the current study, we analyzed 195 reverse transcriptase (RT) sequences obtained from the Los Alamos HIV database. The data were used to assess the course of the viral epidemic over time in the Dominican Republic, using a coalescent approach. Based on the data, we estimated that the timing of the most recent common ancestor (tMRCA) of local HIV-1 subtype B emerged in 1963, approximately. In addition, the Bayesian analysis provided new information that suggests that the epidemic in the Dominican Republic experienced a significant decrease in relative genetic diversity in the past 2 decades. The results suggest that adherence to antiretroviral therapy, adequate prevention campaigns, and better access to health care may be altering the virus's evolution in the Dominican Republic.

  9. Short Communication: HIV-1 Subtype B in the Dominican Republic: Evolution and Molecular Epidemiology

    PubMed Central

    López, Pablo; Rivera-Amill, Vanessa; Paulino-Ramirez, Robert

    2015-01-01

    Abstract The Caribbean region has the world second highest incidence rate of acquired immunodeficiency syndrome. The island of Hispaniola is composed of two sovereign nations: the Dominican Republic and Haiti. Together, they account for more than 85% of HIV/AIDS cases in the Caribbean; and the Dominican Republic alone has approximately 46,000 (33,000–59,000) HIV-1-infected adults and children. Despite this, the magnitude of the genetic variability and evolution of the HIV-1 virus in the Dominican Republic is unclear. In the current study, we analyzed 195 reverse transcriptase (RT) sequences obtained from the Los Alamos HIV database. The data were used to assess the course of the viral epidemic over time in the Dominican Republic, using a coalescent approach. Based on the data, we estimated that the timing of the most recent common ancestor (tMRCA) of local HIV-1 subtype B emerged in 1963, approximately. In addition, the Bayesian analysis provided new information that suggests that the epidemic in the Dominican Republic experienced a significant decrease in relative genetic diversity in the past 2 decades. The results suggest that adherence to antiretroviral therapy, adequate prevention campaigns, and better access to health care may be altering the virus's evolution in the Dominican Republic. PMID:25941939

  10. Membrane-Active Sequences within gp41 Membrane Proximal External Region (MPER) Modulate MPER-Containing Peptidyl Fusion Inhibitor Activity and the Biosynthesis of HIV-1 Structural Proteins

    PubMed Central

    Zhang, Si Min; Jejcic, Alenka; Tam, James P.; Vahlne, Anders

    2015-01-01

    The membrane proximal external region (MPER) is a highly conserved membrane-active region located at the juxtamembrane positions within class I viral fusion glycoproteins and essential for membrane fusion events during viral entry. The MPER in the human immunodeficiency virus type I (HIV-1) envelope protein (Env) interacts with the lipid bilayers through a cluster of tryptophan (Trp) residues and a C-terminal cholesterol-interacting motif. The inclusion of the MPER N-terminal sequence contributes to the membrane reactivity and anti-viral efficacy of the first two anti-HIV peptidyl fusion inhibitors T20 and T1249. As a type I transmembrane protein, Env also interacts with the cellular membranes during its biosynthesis and trafficking. Here we investigated the roles of MPER membrane-active sequences during both viral entry and assembly, specifically, their roles in the design of peptidyl fusion inhibitors and the biosynthesis of viral structural proteins. We found that elimination of the membrane-active elements in MPER peptides, namely, penta Trp→alanine (Ala) substitutions and the disruption of the C-terminal cholesterol-interacting motif through deletion inhibited the anti-viral effect against the pseudotyped HIV-1. Furthermore, as compared to C-terminal dimerization, N-terminal dimerization of MPER peptides and N-terminal extension with five helix-forming residues enhanced their anti-viral efficacy substantially. The secondary structure study revealed that the penta-Trp→Ala substitutions also increased the helical content in the MPER sequence, which prompted us to study the biological relevance of such mutations in pre-fusion Env. We observed that Ala mutations of Trp664, Trp668 and Trp670 in MPER moderately lowered the intracellular and intraviral contents of Env while significantly elevating the content of another viral structural protein, p55/Gag and its derivative p24/capsid. The data suggest a role of the gp41 MPER in the membrane-reactive events during

  11. DNA-stabilized silver nanoclusters and carbon nanoparticles oxide: A sensitive platform for label-free fluorescence turn-on detection of HIV-DNA sequences.

    PubMed

    Ye, Yu-Dan; Xia, Li; Xu, Dang-Dang; Xing, Xiao-Jing; Pang, Dai-Wen; Tang, Hong-Wu

    2016-11-15

    Based on the remarkable difference between the interactions of carbon nanoparticles (CNPs) oxide with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and the fact that fluorescence of DNA-stabilized silver nanoclusters (AgNCs) can be quenched by CNPs oxide, DNA-functionalized AgNCs were applied as label-free fluorescence probes and a novel fluorescence resonance energy transfer (FRET) sensor was successfully constructed for the detection of human immunodeficiency virus (HIV) DNA sequences. CNPs oxide were prepared with the oxidation of candle soot, hence it is simple, time-saving and low-cost. The strategy of dual AgNCs probes was applied to improve the detection sensitivity by using dual- probe capturing the same target DNA in a sandwich mode and as the fluorescence donor, and using CNPs oxide as the acceptor. In the presence of target DNA, a dsDNA hybrid forms, leading to the desorption of the ssDNA-AgNCs probes from CNPs oxide, and the recovering of fluorescence of the AgNCs in a HIV-DNA concentration-dependent manner. The results show that HIV-DNA can be detected in the range of 1-50nM with a detection limit of 0.40nM in aqueous buffer. The method is simple, rapid and sensitive with no need of labeled fluorescent probes, and moreover, the design of fluorescent dual-probe makes full use of the excellent fluorescence property of AgNCs and further improves the detection sensitivity. PMID:27295571

  12. Potential impact of viral load and genetic makeup of HIV type 1 on mother-to-child transmission: characterization of env-C2V3C3 and nef sequences.

    PubMed

    Pádua, Elizabeth; Parreira, Ricardo; Tendeiro, Rita; Nunes, Baltazar; Castela, João; Soares, Isabel; Mouzinho, Ana; Reis, Eduarda; Paixão, Maria Teresa

    2009-11-01

    HIV-1 mother-to-child transmission (MTCT) was evaluated in terms of the molecular characterization of the env and nef genomic regions and quantification of maternal RNA viral loads. Assignment of viral subtype was achieved by direct sequencing of PCR 1172 products amplified from proviral DNA in 45 HIV-1-nontransmitting mothers (NTM), along with 13 pairs of HIV-1-transmitting mothers (TM) and their infected children (C). Analysis of the env C2V3C3 and nef sequences revealed that subtypes G and B, and their genetic combinations (AG, BG), accounted for over 84.5% of all viruses identified. The genetic structure form envA-nefG was the most commonly observed, with a lower frequency in the NTM (13.3%) compared to the TM (23.1%) group. A greater number of genetic forms was observed among NTM, namely the presence of sequences assigned to subtypes D and F, as well as the intergenetic A/J, and C/U, recombinant forms, along with a mosaic provirus with a complex putative envA-nefEGE genetic structure. No significant differences were found when RNA viral loads were evaluated as a function of the viral subtypes. Nevertheless, a relatively high quantification of HIV-1 RNA was obtained in the NTM group, emphasizing the importance of the compliance and effectiveness of therapeutic schemes to control viral replication and reduce the risk of HIV vertical transmission. V3 sequences displaying features associated with the R5 phenotype dominated in both groups. Both C2V3C3 and Nef's functional domains were conserved during HIV-1 vertical transmission.

  13. Potential impact of viral load and genetic makeup of HIV type 1 on mother-to-child transmission: characterization of env-C2V3C3 and nef sequences.

    PubMed

    Pádua, Elizabeth; Parreira, Ricardo; Tendeiro, Rita; Nunes, Baltazar; Castela, João; Soares, Isabel; Mouzinho, Ana; Reis, Eduarda; Paixão, Maria Teresa

    2009-11-01

    HIV-1 mother-to-child transmission (MTCT) was evaluated in terms of the molecular characterization of the env and nef genomic regions and quantification of maternal RNA viral loads. Assignment of viral subtype was achieved by direct sequencing of PCR 1172 products amplified from proviral DNA in 45 HIV-1-nontransmitting mothers (NTM), along with 13 pairs of HIV-1-transmitting mothers (TM) and their infected children (C). Analysis of the env C2V3C3 and nef sequences revealed that subtypes G and B, and their genetic combinations (AG, BG), accounted for over 84.5% of all viruses identified. The genetic structure form envA-nefG was the most commonly observed, with a lower frequency in the NTM (13.3%) compared to the TM (23.1%) group. A greater number of genetic forms was observed among NTM, namely the presence of sequences assigned to subtypes D and F, as well as the intergenetic A/J, and C/U, recombinant forms, along with a mosaic provirus with a complex putative envA-nefEGE genetic structure. No significant differences were found when RNA viral loads were evaluated as a function of the viral subtypes. Nevertheless, a relatively high quantification of HIV-1 RNA was obtained in the NTM group, emphasizing the importance of the compliance and effectiveness of therapeutic schemes to control viral replication and reduce the risk of HIV vertical transmission. V3 sequences displaying features associated with the R5 phenotype dominated in both groups. Both C2V3C3 and Nef's functional domains were conserved during HIV-1 vertical transmission. PMID:19886833

  14. Quantitation of HIV-1 RNA viral load using nucleic acid sequence based amplification methodology and comparison with other surrogate markers for disease progression.

    PubMed

    Sitnik, R; Pinho, J R

    1998-01-01

    In this study, HIV-1 viral blood quantitation determined by Nucleic Acid Sequence Based Amplification (NASBA) was compared with other surrogate disease progression markers (antigen p24, CD4/CD8 cell counts and beta-2 microglobulin) in 540 patients followed up at São Paulo, SP, Brazil. HIV-1 RNA detection was statistically associated with the presence of antigen p24, but the viral RNA was also detected in 68% of the antigen p24 negative samples, confirming that NASBA is much more sensitive than the determination of antigen p24. Regarding other surrogate markers, no statistically significant association with the detection of viral RNA was found. The reproducibility of this viral load assay was assessed by 14 runs of the same sample, using different reagents batches. Viral load values in this sample ranged from 5.83 to 6.27 log (CV = 36%), less than the range (0.5 log) established to the determination of significant viral load changes. PMID:9698880

  15. Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains.

    PubMed

    Zhu, Jiang; Ofek, Gilad; Yang, Yongping; Zhang, Baoshan; Louder, Mark K; Lu, Gabriel; McKee, Krisha; Pancera, Marie; Skinner, Jeff; Zhang, Zhenhai; Parks, Robert; Eudailey, Joshua; Lloyd, Krissey E; Blinn, Julie; Alam, S Munir; Haynes, Barton F; Simek, Melissa; Burton, Dennis R; Koff, Wayne C; Mullikin, James C; Mascola, John R; Shapiro, Lawrence; Kwong, Peter D

    2013-04-16

    Next-generation sequencing of antibody transcripts from HIV-1-infected individuals with broadly neutralizing antibodies could provide an efficient means for identifying somatic variants and characterizing their lineages. Here, we used 454 pyrosequencing and identity/divergence grid sampling to analyze heavy- and light-chain sequences from donor N152, the source of the broadly neutralizing antibody 10E8. We identified variants with up to 28% difference in amino acid sequence. Heavy- and light-chain phylogenetic trees of identified 10E8 variants displayed similar architectures, and 10E8 variants reconstituted from matched and unmatched phylogenetic branches displayed significantly lower autoreactivity when matched. To test the generality of phylogenetic pairing, we analyzed donor International AIDS Vaccine Initiative 84, the source of antibodies PGT141-145. Heavy- and light-chain phylogenetic trees of PGT141-145 somatic variants also displayed remarkably similar architectures; in this case, branch pairings could be anchored by known PGT141-145 antibodies. Altogether, our findings suggest that phylogenetic matching of heavy and light chains can provide a means to approximate natural pairings.

  16. The Analysis of Near Full-Length Genome Sequences of HIV Type 1 Subtype A Viruses from Russia Supports the Monophyly of Major Intrasubtype Clusters

    PubMed Central

    Fernández-García, Aurora; Revilla, Ana; Vázquez-de Parga, Elena; Vinogradova, Anna; Rakhmanova, Aza; Karamov, Eduard; Carrera, Cristina; Delgado, Elena; Pérez-Álvarez, Lucía; Nájera, Rafael; Osmanov, Saladin

    2012-01-01

    Abstract The HIV-1 epidemic in Russia has been insufficiently studied, with only 11 complete genome sequences from this country currently available, only three of which are of the locally predominant genetic form, the former Soviet Union (FSU) subtype A variant (AFSU). Here we analyze 10 newly derived AFSU near full-length genome sequences from Russia. Samples were selected based on phylogenetic clustering in protease-reverse transcriptase in two of the major AFSU clusters, V77IPR (n=6), widely circulating in Russia and other FSU countries, and ASP1 (n=4), predominant in St. Petersburg. The phylogenetic analysis shows that the V77IPR genomes group in a monophyletic cluster together with 10 previously obtained AFSU genome sequences from Uzbekistan, Kazakhstan, Russia, and Cyprus, all bearing the V77I substitution in protease. Similarly, the four ASP1 genomes group in a monophyletic cluster. These results therefore show that the monophyly of V77IPR and ASP1 AFSU clusters is supported in near complete genomes. PMID:22251084

  17. Magic Angle Spinning NMR Reveals Sequence-Dependent Structural Plasticity, Dynamics, and the Spacer Peptide 1 Conformation in HIV-1 Capsid Protein Assemblies

    SciTech Connect

    Han, Yun; Hou, Guangjin; Suiter, Christopher L.; Ahn, Jinwoo; Byeon, In-Ja L.; Lipton, Andrew S.; Burton, Sarah D.; Hung, Ivan; Gorkov, Peter L.; Gan, Zhehong; Brey, William W.; Rice, David M.; Gronenborn, Angela M.; Polenova, Tatyana E.

    2013-11-27

    Maturation of HIV-1 virus into an infectious virion requires cleavage of the Gag polyprotein into its constituent domains and formation of a conical capsid core that encloses viral RNA and a small complement of proteins for replication. The final step of this process is the cleavage of the SP1 peptide from the CA-SP1 maturation intermediate, which triggers the condensation of the CA protein into a conical capsid. The mechanism of this step, including the conformation of the SP1 peptide in CA-SP1, is under intense debate. In this report, we examine the tubular assemblies of CA and the CA-SP1 maturation intermediate using Magic Angle Spinning NMR spectroscopy. At the magnetic fields of 19.9 T and above, tubular CA and CA-SP1 assemblies yield outstanding-quality 2D and 3D MAS NMR spectra, which are amenable to resonance assignments and detailed structural characterization. Dipolar- and scalar-based correlation experiments unequivocally indicate that SP1 peptide is in a random coil conformation and mobile in the assembled CA-SP1. Analysis of two sequence variants reveals that remarkably, the conformation of SP1 tail, of the functionally important CypA loop, and of the loop preceding helix 8 are sequence dependent and modulated by the residue variations at distal sites. These findings challenge the role of SP1 as a conformational switch in the maturation process and establish sequence-dependent conformational plasticity in CA.

  18. IDEPI: rapid prediction of HIV-1 antibody epitopes and other phenotypic features from sequence data using a flexible machine learning platform.

    PubMed

    Hepler, N Lance; Scheffler, Konrad; Weaver, Steven; Murrell, Ben; Richman, Douglas D; Burton, Dennis R; Poignard, Pascal; Smith, Davey M; Kosakovsky Pond, Sergei L

    2014-09-01

    Since its identification in 1983, HIV-1 has been the focus of a research effort unprecedented in scope and difficulty, whose ultimate goals--a cure and a vaccine--remain elusive. One of the fundamental challenges in accomplishing these goals is the tremendous genetic variability of the virus, with some genes differing at as many as 40% of nucleotide positions among circulating strains. Because of this, the genetic bases of many viral phenotypes, most notably the susceptibility to neutralization by a particular antibody, are difficult to identify computationally. Drawing upon open-source general-purpose machine learning algorithms and libraries, we have developed a software package IDEPI (IDentify EPItopes) for learning genotype-to-phenotype predictive models from sequences with known phenotypes. IDEPI can apply learned models to classify sequences of unknown phenotypes, and also identify specific sequence features which contribute to a particular phenotype. We demonstrate that IDEPI achieves performance similar to or better than that of previously published approaches on four well-studied problems: finding the epitopes of broadly neutralizing antibodies (bNab), determining coreceptor tropism of the virus, identifying compartment-specific genetic signatures of the virus, and deducing drug-resistance associated mutations. The cross-platform Python source code (released under the GPL 3.0 license), documentation, issue tracking, and a pre-configured virtual machine for IDEPI can be found at https://github.com/veg/idepi. PMID:25254639

  19. Phage randomization in a charybdotoxin scaffold leads to CD4-mimetic recognition motifs that bind HIV-1 envelope through non-aromatic sequences.

    PubMed

    Li, C; Dowd, C S; Zhang, W; Chaiken, I M

    2001-06-01

    Binding of HIV-1 gp120 to T-cell receptor CD4 initiates conformational changes in the viral envelope that trigger viral entry into host cells. Phage epitope randomization of a beta-turn loop of a charybdotoxin-based miniprotein scaffold was used to identify peptides that can bind gp120 and block the gp120-CD4 interaction. We describe here the display of the charybdotoxin scaffold on the filamentous phage fUSE5, its use to construct a beta-turn library, and miniprotein sequences identified through library panning with immobilized Env gp120. Competition enzyme-linked immunosorbent assay (ELISA) identified high-frequency phage selectants for which specific gp120 binding was competed by sCD4. Several of these selectants contain hydrophobic residues in place of the Phe that occurs in the gp120-binding beta-turns of both CD4 and previously identified scorpion toxin CD4 mimetics. One of these selectants, denoted TXM[24GQTL27], contains GQTL in place of the CD4 beta-turn sequence 40QGSF43. TXM[24GQTL27] peptide was prepared using solid-phase chemical synthesis, its binding to gp120 demonstrated by optical biosensor kinetics analysis and its affinity for the CD4 binding site of gp120 confirmed by competition ELISA. The results demonstrate that aromatic-less loop-containing CD4 recognition mimetics can be formed with detectable envelope protein binding within a beta-turn of the charybdotoxin miniprotein scaffold. The results of this work establish a methodology for phage display of a charybdotoxin miniprotein scaffold and point to the potential value of phage-based epitope randomization of this miniprotein for identifying novel CD4 mimetics. The latter are potentially useful in deconvoluting structural determinants of CD4-HIV envelope recognition and possibly in designing antagonists of viral entry. PMID:11437954

  20. Deep sequencing analysis of HIV-1 reverse transcriptase at baseline and time of failure in patients receiving rilpivirine in the phase III studies ECHO and THRIVE.

    PubMed

    Van Eygen, Veerle; Thys, Kim; Van Hove, Carl; Rimsky, Laurence T; De Meyer, Sandra; Aerssens, Jeroen; Picchio, Gaston; Vingerhoets, Johan

    2016-05-01

    Minority variants (1.0-25.0%) were evaluated by deep sequencing (DS) at baseline and virological failure (VF) in a selection of antiretroviral treatment-naïve, HIV-1-infected patients from the rilpivirine ECHO/THRIVE phase III studies. Linkage between frequently emerging resistance-associated mutations (RAMs) was determined. DS (llIumina®) and population sequencing (PS) results were available at baseline for 47 VFs and time of failure for 48 VFs; and at baseline for 49 responders matched for baseline characteristics. Minority mutations were accurately detected at frequencies down to 1.2% of the HIV-1 quasispecies. No baseline minority rilpivirine RAMs were detected in VFs; one responder carried 1.9% F227C. Baseline minority mutations associated with resistance to other non-nucleoside reverse transcriptase inhibitors (NNRTIs) were detected in 8/47 VFs (17.0%) and 7/49 responders (14.3%). Baseline minority nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) RAMs M184V and L210W were each detected in one VF (none in responders). At failure, two patients without NNRTI RAMs by PS carried minority rilpivirine RAMs K101E and/or E138K; and five additional patients carried other minority NNRTI RAMs V90I, V106I, V179I, V189I, and Y188H. Overall at failure, minority NNRTI RAMs and NRTI RAMs were found in 29/48 (60.4%) and 16/48 VFs (33.3%), respectively. Linkage analysis showed that E138K and K101E were usually not observed on the same viral genome. In conclusion, baseline minority rilpivirine RAMs and other NNRTI/NRTI RAMs were uncommon in the rilpivirine arm of the ECHO and THRIVE studies. DS at failure showed emerging NNRTI resistant minority variants in seven rilpivirine VFs who had no detectable NNRTI RAMs by PS. PMID:26412111

  1. Sequence-based design and discovery of peptide inhibitors of HIV-1 integrase: insight into the binding mode of the enzyme.

    PubMed

    Li, Hui-Yuan; Zawahir, Zahrah; Song, Lai-Dong; Long, Ya-Qiu; Neamati, Nouri

    2006-07-27

    Integration of viral DNA into the host chromosome is an essential step in the HIV life cycle. This process is mediated by integrase (IN), a 32 kDa viral enzyme that has no mammalian counterpart, rendering it an attractive target for antiviral drug design. Herein, we present a novel approach toward elucidating "hot spots" of protein-protein or protein-nucleic acid interactions of IN through the design of peptides that encompass conserved amino acids and residues known to be important for enzymatic activity. We designed small peptides (7-17 residues) containing at least one amino acid residue that is important for IN catalytic activities (3'-processing and strand transfer) or viral replication. All these peptides were synthesized on solid phase by fluorenylmethoxycarbonyl (Fmoc) chemistry and evaluated for their inhibition of IN catalytic activities. Such specific sites of interest (i.e., protein-DNA or protein-drug interactions) could potentially be used as drug targets. This novel "sequence walk" strategy across the entire 288 residues of IN has allowed the identification of two peptides NL-6 and NL-9 with 50% inhibitory concentration (IC50) values of 2.7 and 56 microM for strand transfer activity, respectively. Amino acid substitution analysis on these peptides revealed essential residues for activity, and the rational truncation of NL-6 produced a novel hexapeptide (peptide NL6-5) with inhibitory potency equal to that of the parent dodecapeptide (peptide NL-6). More significantly, the retroinverso analogue of NL-6 (peptide RDNL-6) in which the direction of the sequence is reversed and the chirality of each amino acid residue is inverted displayed improved inhibitory potency against 3'-processing of HIV-1 IN by 6-fold relative to the parent NL-6, serving as a metabolically stable derivative for further in vitro and in vivo analyses.

  2. Los Alamos Critical Assemblies Facility

    SciTech Connect

    Malenfant, R.E.

    1981-06-01

    The Critical Assemblies Facility of the Los Alamos National Laboratory has been in existence for thirty-five years. In that period, many thousands of measurements have been made on assemblies of /sup 235/U, /sup 233/U, and /sup 239/Pu in various configurations, including the nitrate, sulfate, fluoride, carbide, and oxide chemical compositions and the solid, liquid, and gaseous states. The present complex of eleven operating machines is described, and typical applications are presented.

  3. Next-Generation Sequencing of Small RNAs from HIV-Infected Cells Identifies Phased microRNA Expression Patterns and Candidate Novel microRNAs Differentially Expressed upon Infection

    PubMed Central

    Chang, Stewart T.; Thomas, Matthew J.; Sova, Pavel; Green, Richard R.; Palermo, Robert E.; Katze, Michael G.

    2013-01-01

    ABSTRACT HIV infection of CD4+ T cells induces a range of host transcriptional changes in mRNAs as well as microRNAs that may coordinate changes in mRNAs. To survey these dynamic changes, we applied next-generation sequencing, analyzing the small RNA fraction of HIV-infected cells at 5, 12, and 24 h postinfection (RNA-Seq). These time points afforded a view of the transcriptomic changes occurring both before and during viral replication. In the resulting small RNA-Seq data set, we detected a phased pattern of microRNA expression. Largely distinct sets of microRNAs were found to be suppressed at 5 and 12 h postinfection, and both sets of changes rebounded later in infection. A larger set of microRNA changes was observed at 24 h postinfection. When integrated with mRNA expression data, the small RNA-Seq data indicated a role for microRNAs in transcriptional regulation, T cell activation, and cell cycle during HIV infection. As a unique benefit of next-generation sequencing, we also detected candidate novel host microRNAs differentially expressed during infection, including one whose downregulation at 24 h postinfection may allow full replication of HIV to proceed. Collectively, our data provide a uniquely comprehensive view of the changes in host microRNAs induced by HIV during cellular infection. PMID:23386435

  4. Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

    SciTech Connect

    Anastassopoulou, Cleo G.; Ketas, Thomas J.; Sanders, Rogier W.; Johan Klasse, Per; Moore, John P.

    2012-07-05

    A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.

  5. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

    DOE PAGES

    Hraber, Peter; Korber, Bette; Wagh, Kshitij; Giorgi, Elena; Bhattacharya, Tanmoy; Gnanakaran, S.; Lapedes, Alan S.; Learn, Gerald H.; Kreider, Edward F.; Li, Yingying; et al

    2015-10-21

    Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

  6. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

    SciTech Connect

    Hraber, Peter; Korber, Bette; Wagh, Kshitij; Giorgi, Elena; Bhattacharya, Tanmoy; Gnanakaran, S.; Lapedes, Alan S.; Learn, Gerald H.; Kreider, Edward F.; Li, Yingying; Shaw, George M.; Hahn, Beatrice H.; Montefiori, David C.; Alam, S. Munir; Bonsignori, Mattia; Moody, M. Anthony; Liao, Hua-Xin; Gao, Feng; Haynes, Barton

    2015-10-21

    Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations of mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.

  7. Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis

    PubMed Central

    Rhee, Soo-Yon; Blanco, Jose Luis; Jordan, Michael R.; Taylor, Jonathan; Lemey, Philippe; Varghese, Vici; Hamers, Raph L.; Bertagnolio, Silvia; de Wit, Tobias F. Rinke; Aghokeng, Avelin F.; Albert, Jan; Avi, Radko; Avila-Rios, Santiago; Bessong, Pascal O.; Brooks, James I.; Boucher, Charles A. B.; Brumme, Zabrina L.; Busch, Michael P.; Bussmann, Hermann; Chaix, Marie-Laure; Chin, Bum Sik; D’Aquin, Toni T.; De Gascun, Cillian F.; Derache, Anne; Descamps, Diane; Deshpande, Alaka K.; Djoko, Cyrille F.; Eshleman, Susan H.; Fleury, Herve; Frange, Pierre; Fujisaki, Seiichiro; Harrigan, P. Richard; Hattori, Junko; Holguin, Africa; Hunt, Gillian M.; Ichimura, Hiroshi; Kaleebu, Pontiano; Katzenstein, David; Kiertiburanakul, Sasisopin; Kim, Jerome H.; Kim, Sung Soon; Li, Yanpeng; Lutsar, Irja; Morris, Lynn; Ndembi, Nicaise; NG, Kee Peng; Paranjape, Ramesh S.; Peeters, Martine; Poljak, Mario; Price, Matt A.; Ragonnet-Cronin, Manon L.; Reyes-Terán, Gustavo; Rolland, Morgane; Sirivichayakul, Sunee; Smith, Davey M.; Soares, Marcelo A.; Soriano, Vincent V.; Ssemwanga, Deogratius; Stanojevic, Maja; Stefani, Mariane A.; Sugiura, Wataru; Sungkanuparph, Somnuek; Tanuri, Amilcar; Tee, Kok Keng; Truong, Hong-Ha M.; van de Vijver, David A. M. C.; Vidal, Nicole; Yang, Chunfu; Yang, Rongge; Yebra, Gonzalo; Ioannidis, John P. A.; Vandamme, Anne-Mieke; Shafer, Robert W.

    2015-01-01

    Background Regional and subtype-specific mutational patterns of HIV-1 transmitted drug resistance (TDR) are essential for informing first-line antiretroviral (ARV) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. We sought to understand the molecular epidemiology of TDR and to identify the HIV-1 drug-resistance mutations responsible for TDR in different regions and virus subtypes. Methods and Findings We reviewed all GenBank submissions of HIV-1 reverse transcriptase sequences with or without protease and identified 287 studies published between March 1, 2000, and December 31, 2013, with more than 25 recently or chronically infected ARV-naïve individuals. These studies comprised 50,870 individuals from 111 countries. Each set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations (SDRMs). The median overall TDR prevalence in sub-Saharan Africa (SSA), south/southeast Asia (SSEA), upper-income Asian countries, Latin America/Caribbean, Europe, and North America was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. In SSA, there was a yearly 1.09-fold (95% CI: 1.05–1.14) increase in odds of TDR since national ARV scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. The odds of NNRTI-associated TDR also increased in Latin America/Caribbean (odds ratio [OR] = 1.16; 95% CI: 1.06–1.25), North America (OR = 1.19; 95% CI: 1.12–1.26), Europe (OR = 1.07; 95% CI: 1.01–1.13), and upper-income Asian countries (OR = 1.33; 95% CI: 1.12–1.55). In SSEA, there was no significant change in the odds of TDR since national ARV scale-up (OR = 0.97; 95% CI: 0.92–1.02). An analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions—a proxy for recent infection—yielded trends comparable to those obtained using the complete dataset. Four

  8. Los Alamos Science: Number 16

    SciTech Connect

    Cooper, N.G.

    1988-01-01

    It was an unusually stimulating day and a half at Los Alamos when two Nobel Laureates in physiology, a leading paleontologist, and a leading bio-astrophysicist came together to discuss ''Unsolved Problems in the Science of Life,'' the topic of the second in a series of special meetings sponsored by the Fellows of the Laboratory. Just like the first one on ''Creativity in Science,'' this colloquium took us into a broader arena of ideas and viewpoints than is our usual daily fare. To contemplate the evolution and mysteries of intelligent life from the speakers' diverse points of view at one time, in one place was indeed a rare experience.

  9. Differential evolution of a CXCR4-using HIV-1 strain in CCR5wt/wt and CCR5∆32/∆32 hosts revealed by longitudinal deep sequencing and phylogenetic reconstruction

    PubMed Central

    Le, Anh Q.; Taylor, Jeremy; Dong, Winnie; McCloskey, Rosemary; Woods, Conan; Danroth, Ryan; Hayashi, Kanna; Milloy, M.-J.; Poon, Art F. Y.; Brumme, Zabrina L.

    2015-01-01

    Rare individuals homozygous for a naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5∆32/∆32) are resistant to infection by CCR5-using (“R5”) HIV-1 strains but remain susceptible to less common CXCR4-using (“X4”) strains. The evolutionary dynamics of X4 infections however, remain incompletely understood. We identified two individuals, one CCR5wt/wt and one CCR5∆32/∆32, within the Vancouver Injection Drug Users Study who were infected with a genetically similar X4 HIV-1 strain. While early-stage plasma viral loads were comparable in the two individuals (~4.5–5 log10 HIV-1 RNA copies/ml), CD4 counts in the CCR5wt/wt individual reached a nadir of <20 CD4 cells/mm3 within 17 months but remained >250 cells/mm3 in the CCR5∆32/∆32 individual. Ancestral phylogenetic reconstructions using longitudinal envelope-V3 deep sequences suggested that both individuals were infected by a single transmitted/founder (T/F) X4 virus that differed at only one V3 site (codon 24). While substantial within-host HIV-1 V3 diversification was observed in plasma and PBMC in both individuals, the CCR5wt/wt individual’s HIV-1 population gradually reverted from 100% X4 to ~60% R5 over ~4 years whereas the CCR5∆32/∆32 individual’s remained consistently X4. Our observations illuminate early dynamics of X4 HIV-1 infections and underscore the influence of CCR5 genotype on HIV-1 V3 evolution. PMID:26631642

  10. High-throughput sequence analysis reveals structural diversity and improved potency among RNA inhibitors of HIV reverse transcriptase

    PubMed Central

    Ditzler, Mark A.; Lange, Margaret J.; Bose, Debojit; Bottoms, Christopher A.; Virkler, Katherine F.; Sawyer, Andrew W.; Whatley, Angela S.; Spollen, William; Givan, Scott A.; Burke, Donald H.

    2013-01-01

    Systematic evolution of ligands through exponential enrichment (SELEX) is a well-established method for generating nucleic acid populations that are enriched for specified functions. High-throughput sequencing (HTS) enhances the power of comparative sequence analysis to reveal details of how RNAs within these populations recognize their targets. We used HTS analysis to evaluate RNA populations selected to bind type I human immunodeficiency virus reverse transcriptase (RT). The populations are enriched in RNAs of independent lineages that converge on shared motifs and in clusters of RNAs with nearly identical sequences that share common ancestry. Both of these features informed inferences of the secondary structures of enriched RNAs, their minimal structural requirements and their stabilities in RT-aptamer complexes. Monitoring population dynamics in response to increasing selection pressure revealed RNA inhibitors of RT that are more potent than the previously identified pseudoknots. Improved potency was observed for inhibition of both purified RT in enzymatic assays and viral replication in cell-based assays. Structural and functional details of converged motifs that are obscured by simple consensus descriptions are also revealed by the HTS analysis. The approach presented here can readily be generalized for the efficient and systematic post-SELEX development of aptamers for down-stream applications. PMID:23241386

  11. Los Alamos Science: The Human Genome Project. Number 20, 1992

    DOE R&D Accomplishments Database

    Cooper, N. G.; Shea, N. eds.

    1992-01-01

    This document provides a broad overview of the Human Genome Project, with particular emphasis on work being done at Los Alamos. It tries to emphasize the scientific aspects of the project, compared to the more speculative information presented in the popular press. There is a brief introduction to modern genetics, including a review of classic work. There is a broad overview of the Genome Project, describing what the project is, what are some of its major five-year goals, what are major technological challenges ahead of the project, and what can the field of biology, as well as society expect to see as benefits from this project. Specific results on the efforts directed at mapping chromosomes 16 and 5 are discussed. A brief introduction to DNA libraries is presented, bearing in mind that Los Alamos has housed such libraries for many years prior to the Genome Project. Information on efforts to do applied computational work related to the project are discussed, as well as experimental efforts to do rapid DNA sequencing by means of single-molecule detection using applied spectroscopic methods. The article introduces the Los Alamos staff which are working on the Genome Project, and concludes with brief discussions on ethical, legal, and social implications of this work; a brief glimpse of genetics as it may be practiced in the next century; and a glossary of relevant terms.

  12. Los Alamos Science: The Human Genome Project. Number 20, 1992

    SciTech Connect

    Cooper, N G; Shea, N

    1992-01-01

    This article provides a broad overview of the Human Genome Project, with particular emphasis on work being done at Los Alamos. It tries to emphasize the scientific aspects of the project, compared to the more speculative information presented in the popular press. There is a brief introduction to modern genetics, including a review of classic work. There is a broad overview of the Genome Project, describing what the project is, what are some of its major five-year goals, what are major technological challenges ahead of the project, and what can the field of biology, as well as society expect to see as benefits from this project. Specific results on the efforts directed at mapping chromosomes 16 and 5 are discussed. A brief introduction to DNA libraries is presented, bearing in mind that Los Alamos has housed such libraries for many years prior to the Genome Project. Information on efforts to do applied computational work related to the project are discussed, as well as experimental efforts to do rapid DNA sequencing by means of single-molecule detection using applied spectroscopic methods. The article introduces the Los Alamos staff which are working on the Genome Project, and concludes with brief discussions on ethical, legal, and social implications of this work; a brief glimpse of genetics as it may be practiced in the next century; and a glossary of relevant terms.

  13. Magic angle spinning NMR reveals sequence-dependent structural plasticity, dynamics, and the spacer peptide 1 conformation in HIV-1 capsid protein assemblies.

    PubMed

    Han, Yun; Hou, Guangjin; Suiter, Christopher L; Ahn, Jinwoo; Byeon, In-Ja L; Lipton, Andrew S; Burton, Sarah; Hung, Ivan; Gor'kov, Peter L; Gan, Zhehong; Brey, William; Rice, David; Gronenborn, Angela M; Polenova, Tatyana

    2013-11-27

    A key stage in HIV-1 maturation toward an infectious virion requires sequential proteolytic cleavage of the Gag polyprotein leading to the formation of a conical capsid core that encloses the viral RNA genome and a small complement of proteins. The final step of this process involves severing the SP1 peptide from the CA-SP1 maturation intermediate, which triggers the condensation of the CA protein into the capsid shell. The details of the overall mechanism, including the conformation of the SP1 peptide in CA-SP1, are still under intense debate. In this report, we examine tubular assemblies of CA and the CA-SP1 maturation intermediate using magic angle spinning (MAS) NMR spectroscopy. At magnetic fields of 19.9 T and above, outstanding quality 2D and 3D MAS NMR spectra were obtained for tubular CA and CA-SP1 assemblies, permitting resonance assignments for subsequent detailed structural characterization. Dipolar- and scalar-based correlation experiments unequivocally indicate that SP1 peptide is in a random coil conformation and mobile in the assembled CA-SP1. Analysis of two CA protein sequence variants reveals that, unexpectedly, the conformations of the SP1 tail, the functionally important CypA loop, and the loop preceding helix 8 are modulated by residue variations at distal sites. These findings provide support for the role of SP1 as a trigger of the disassembly of the immature CA capsid for its subsequent de novo reassembly into mature cores and establish the importance of sequence-dependent conformational plasticity in CA assembly.

  14. Magic Angle Spinning NMR Reveals Sequence-Dependent Structural Plasticity, Dynamics, and the Spacer Peptide 1 Conformation in HIV-1 Capsid Protein Assemblies

    PubMed Central

    Han, Yun; Hou, Guangjin; Suiter, Christopher L.; Ahn, Jinwoo; Byeon, In-Ja L.; Lipton, Andrew S.; Burton, Sarah; Hung, Ivan; Gor’kov, Peter L.; Gan, Zhehong; Brey, William; Rice, David; Gronenborn, Angela M.; Polenova, Tatyana

    2013-01-01

    A key stage in HIV-1 maturation towards an infectious virion requires sequential proteolytic cleavage of the Gag polyprotein leading to the formation of a conical capsid core that encloses the viral RNA genome and a small complement of proteins. The final step of this process involves severing the SP1 peptide from the CA-SP1 maturation intermediate, which triggers the condensation of the CA protein into the capsid shell. The details of the overall mechanism, including the conformation of the SP1 peptide in CA-SP1, are still under intense debate. In this report, we examine tubular assemblies of CA and the CA-SP1 maturation intermediates using Magic Angle Spinning NMR spectroscopy. At magnetic fields of 19.9 T and above, outstanding-quality 2D and 3D MAS NMR spectra were obtained for tubular CA and CA-SP1 assemblies yield, permitting resonance assignments for subsequent detailed structural characterization. Dipolar- and scalar-based correlation experiments unequivocally indicate that SP1 peptide is in a random coil conformation and mobile in the assembled CA-SP1. Analysis of two CA protein sequence variants reveals that, unexpectedly, the conformations of the SP1 tail, the functionally important CypA loop, and the loop preceding helix 8 are modulated by residue variations at distal sites. These findings provide support for the role of SP1 as a trigger of the disassembly of the immature CA capsid for its subsequent de novo reassembly into mature cores, and establish the importance of sequence-dependent conformational plasticity in CA assembly. PMID:24164646

  15. Los Alamos opacity web page

    SciTech Connect

    Magee, N.H. Jr.; Clark, R.E.H.

    1998-02-01

    The Los Alamos opacity data base is now available on the World Wide Web at http://t4.lanl.gov. The data base contains both the original Astrophysical Opacity Library distributed worldwide in the 1980`s (for historical reference) and the new improved opacities from the Light Element Detailed Configuration OPacity (LEDCOP) code. Users can access the opacity data using the multigroup opacity code TOPS to obtain Rosseland and Planck gray opacities, group mean opacities over selected energy ranges, the monochromatic absorption coefficients and the average ionization over a wide range of temperatures and densities. As described in this paper, these quantities are available for all of the elements presently on the data base and TOPS will provide the same quantities for any arbitrary mixture of these elements.

  16. Los Alamos PC estimating system

    SciTech Connect

    Stutz, R.A.; Lemon, G.D.

    1987-01-01

    The Los Alamos Cost Estimating System (QUEST) is being converted to run on IBM personal computers. This very extensive estimating system is capable of supporting cost estimators from many different and varied fields. QUEST does not dictate any fixed method for estimating. QUEST supports many styles and levels of detail estimating. QUEST can be used with or without data bases. This system allows the estimator to provide reports based on levels of detail defined by combining work breakdown structures. QUEST provides a set of tools for doing any type of estimate without forcing the estimator to use any given method. The level of detail in the estimate can be mixed based on the amount of information known about different parts of the project. The system can support many different data bases simultaneously. Estimators can modify any cost in any data base.

  17. Comparison of 454 Ultra-Deep Sequencing and Allele-Specific Real-Time PCR with Regard to the Detection of Emerging Drug-Resistant Minor HIV-1 Variants after Antiretroviral Prophylaxis for Vertical Transmission

    PubMed Central

    Hauser, Andrea; Kuecherer, Claudia; Kunz, Andrea; Dabrowski, Piotr Wojtek; Radonić, Aleksandar; Nitsche, Andreas; Theuring, Stefanie; Bannert, Norbert; Sewangi, Julius; Mbezi, Paulina; Dugange, Festo; Harms, Gundel; Meixenberger, Karolin

    2015-01-01

    Background Pregnant HIV-infected women were screened for the development of HIV-1 drug resistance after implementation of a triple-antiretroviral transmission prophylaxis as recommended by the WHO in 2006. The study offered the opportunity to compare amplicon-based 454 ultra-deep sequencing (UDS) and allele-specific real-time PCR (ASPCR) for the detection of drug-resistant minor variants in the HIV-1 reverse transcriptase (RT). Methods Plasma samples from 34 Tanzanian women were previously analysed by ASPCR for key resistance mutations in the viral RT selected by AZT, 3TC, and NVP (K70R, K103N, Y181C, M184V, T215Y/F). In this study, the RT region of the same samples was investigated by amplicon-based UDS for resistance mutations using the 454 GS FLX System. Results Drug-resistant HIV-variants were identified in 69% (20/29) of women by UDS and in 45% (13/29) by ASPCR. The absolute number of resistance mutations identified by UDS was twice that identified by ASPCR (45 vs 24). By UDS 14 of 24 ASPCR-detected resistance mutations were identified at the same position. The overall concordance between UDS and ASPCR was 61.0% (25/41). The proportions of variants quantified by UDS were approximately 2–3 times lower than by ASPCR. Amplicon generation from samples with viral loads below 20,000 copies/ml failed more frequently by UDS compared to ASPCR (limit of detection = 650 copies/ml), resulting in missing or insufficient sequence coverage. Conclusions Both methods can provide useful information about drug-resistant minor HIV-1 variants. ASPCR has a higher sensitivity than UDS, but is restricted to single resistance mutations. In contrast, UDS is limited by its requirement for high viral loads to achieve sufficient sequence coverage, but the sequence information reveals the complete resistance patterns within the genomic region analysed. Improvements to the UDS limit of detection are in progress, and UDS could then facilitate monitoring of drug-resistant minor variants in

  18. Analysis of sequences of hepatitis C virus NS5A genotype 1 in HIV-coinfected patients with a null response to nitazoxanide or peg-interferon plus ribavirin.

    PubMed

    Sede, M; Laufer, N; Ojeda, D; Gun, A; Cahn, P; Quarleri, J

    2013-09-01

    Even though new drugs have been approved for treatment of hepatitis C virus (HCV) infection, the risk of drug-drug interactions and concern about overlapping toxicities has hindered the development of studies in HIV/HCV-coinfected individuals. Traditional treatment with pegylated interferon plus ribavirin (peg-IFN + RBV) is very expensive and has a low rate of sustained virological response in coinfected patients, especially if they are infected with HCV genotype 1. Nitazoxanide (NTZ) is a drug that is being evaluated for the treatment of chronic HCV infection, both in HCV-monoinfected and HIV/HCV-coinfected patients. Understanding the NTZ resistance mechanism could allow the development of resistance to be minimized and would expand the treatment options, mainly in special populations such as HIV/HCV-coinfected patients. Similarly to IFN, NTZ increases the activity of the cellular protein kinase activated by double-stranded RNA (PKR), a key kinase in the innate antiviral response. In order to elucidate whether sequence heterogeneity in the PKR-binding domain of HCV NS5A genotype 1 could influence the antiviral activity of either NTZ monotherapy or peg-IFN + RBV, baseline and end-of-therapy plasma samples from two groups of eleven non-responder HIV/HCV-coinfected patients that had received NTZ or peg-IFN + RBV were studied. Most of the HCV NS5A sequences examined at the end of therapy did not change from the baseline, even after 30 days course of antiviral therapy. An extensive comparison of HCV NS5A genotype 1 and 4 sequences from the database with reported IFN therapy outcome was performed in order to infer their phylogenetic relationships. The HCV genotype 1 NS5A nucleotide sequences from therapy-non-responder patients were intermingled amongst those from the database, irrespective of their IFN-therapy outcome. When comparing NS5A-PKRBD amino acid sequences, significant differences were observed in genotype 4, but not in genotype 1 (p < 0.0001 and p

  19. HIV Symptoms

    MedlinePlus

    ... Submit Home > HIV/AIDS > What is HIV/AIDS? HIV/AIDS This information in Spanish ( en español ) HIV symptoms Photo courtesy of AIDS.gov More information ... and brain Return to top More information on HIV symptoms Explore other publications and websites Basic Information ...

  20. HIV Molecular Immunology 2014

    SciTech Connect

    Yusim, Karina; Korber, Bette Tina Marie; Barouch, Dan; Koup, Richard; de Boer, Rob; Moore, John P.; Brander, Christian; Haynes, Barton F.; Walker, Bruce D.

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  1. Towards Experimental Annotation of Genes by High Throughput Sequencing

    SciTech Connect

    Bradbury, Andrew

    2010-06-03

    Andrew Bradbury of Los Alamos National Laboratory discusses turning annotation into a sequencing pipeline on June 3, 2010 at the "Sequencing, Finishing, Analysis in the Future" meeting in Santa Fe, NM

  2. Reconstituting the epidemic history of mono lineage of HIV-1 CRF01_AE in Guizhou province, Southern China.

    PubMed

    Zeng, Haiyan; Sun, Binlian; Li, Lingnuo; Li, Yanpeng; Liu, Yong; Xiao, Yao; Jiang, Yan; Yang, Rongge

    2014-08-01

    Guizhou province, located between border provinces and Central province of China, plays a crucial role in the transmission of HIV-1, implying it is important to monitor the epidemic of HIV-1 in this region. Available HIV-1 infected patients' plasma (n=78) were collected from Tongren city, Eastern Guizhou. Full-length gag, partial pol and env gene sequences were amplified and analyzed using phylogenetic, recombinant and Bayesian molecular clock approaches. Phylogenetic and recombinant analyses showed that CRF01_AE predominated among injecting drug users and heterosexuals in Tongren city with 85.9% proportion, it was followed by B' (5.1%), CRF07_BC (3.8%), CRF08_BC (3.8%), and B (1.3%). Moreover, 98.5% of CRF01_AE strains belonged to the distinct lineage CRF01_AE-v previously found in Guangxi province. To infer the most probable origin of CRF01_AE-v in Guizhou province, we download all available full length of CRF01_AE gag, pol and env gene region sequences from China in Los Alamos HIV sequence database. Phylodynamic and phylogeographic analyses revealed that the expanding CRF01_AE-v epidemic in Guizhou province was the result of local epidemic driven by multiple independent introductions of CRF01_AE-v strains from Guangxi province in early 2000s. High prevalence of CRF01_AE in Guizhou province may bridge the epidemic to Central China. It provides a new insight for the understanding of HIV-1 epidemic in Guizhou province and makes the evolutionary history of CRF01_AE in China more intact.

  3. Sunset at the ALaMO

    NASA Video Gallery

    A new color all-sky camera has opened its eyes at the ALaMO, or Automated Lunar and Meteor Observatory, at NASA's Marshall Space Flight Center in Huntsville, Ala. Watch its inaugural video below, s...

  4. Publications of Los Alamos research 1988

    SciTech Connect

    Varjabedian, K.; Dussart, S.A.; McClary, W.J.; Rich, J.A.

    1989-12-01

    This bibliography lists unclassified publications of work done at the Los Alamos National Laboratory for 1988. The entries, which are subdivided by broad subject categories, are cross-referenced with an author index and a numeric index.

  5. New Rad Lab for Los Alamos

    SciTech Connect

    2008-08-06

    The topping out ceremony for a key construction stage in the Los Alamos National Laboratory's newest facility, the Radiological Laboratory Utility & Office Building. This is part of the National Nu...  

  6. Environmental surveillance at Los Alamos during 1994

    SciTech Connect

    1996-07-01

    This report describes environmental monitoring activities at Los Alamos National Laboratory for 1994. Data were collected to assess external penetrating radiation, airborne emissions, liquid effluents, radioactivity of environmental materials and food stuffs, and environmental compliance.

  7. New Rad Lab for Los Alamos

    ScienceCinema

    None

    2016-07-12

    The topping out ceremony for a key construction stage in the Los Alamos National Laboratory's newest facility, the Radiological Laboratory Utility & Office Building. This is part of the National Nu...  

  8. HIV Prevention

    MedlinePlus

    ... to treat HIV infection (called antiretroviral therapy, or ART) the right way, every day and his or ... way, every day, the medicine to treat HIV (ART) reduces the amount of HIV (called “viral ...

  9. Edward Teller Returns to LOS Alamos

    NASA Astrophysics Data System (ADS)

    Hecker, Siegfried S.

    2010-01-01

    I was asked to share some reflections of Edward Teller's return to Los Alamos during my directorship. I met Teller late in his life. My comments focus on that time and they will be mostly in the form of stories of my interactions and those of my colleagues with Teller. Although the focus of this symposium is on Teller's contributions to science, at Los Alamos it was never possible to separate Teller's science from policy and controversy ...

  10. Internship at Los Alamos National Laboratory

    SciTech Connect

    Dunham, Ryan Q.

    2012-07-11

    Los Alamos National Laboratory (LANL) is located in Los Alamos, New Mexico. It provides support for our country's nuclear weapon stockpile as well as many other scientific research projects. I am an Undergraduate Student Intern in the Systems Design and Analysis group within the Nuclear Nonproliferation division of the Global Security directorate at LANL. I have been tasked with data analysis and modeling of particles in a fluidized bed system for the capture of carbon dioxide from power plant flue gas.

  11. Zinc- and sequence-dependent binding to nucleic acids by the N-terminal zinc finger of the HIV-1 nucleocapsid protein: NMR structure of the complex with the Psi-site analog, dACGCC.

    PubMed

    South, T L; Summers, M F

    1993-01-01

    The nucleic acid interactive properties of a synthetic peptide with sequence of the N-terminal CCHC zinc finger (CCHC = Cys-X2-Cys-X4-His-X4-Cys; X = variable amino acid) of the human immunodeficiency virus (HIV) nucleocapsid protein, Zn(HIV1-F1), have been studied by 1H NMR spectroscopy. Titration of Zn(HIV1-F1) with oligodeoxyribonucleic acids containing different nucleotide sequences reveals, for the first time, sequence-dependent binding that requires the presence of at least one guanosine residue for tight complex formation. The dynamics of complex formation are sensitive to the nature of the residues adjacent to guanosine, with residues on the 3' side of guanosine having the largest influence. An oligodeoxyribonucleotide with sequence corresponding to a portion of the HIV-1 psi-packaging signal, d(ACGCC), forms a relatively tight complex with Zn(HIV1-F1) (Kd = 5 x 10(-6) M). Two-dimensional nuclear Overhauser effect (NOESY) data indicate that the bound nucleic acid exists predominantly in a single-stranded, A-helical conformation, and the presence of more than a dozen intermolecular NOE cross peaks enabled three-dimensional modeling of the complex. The nucleic acid binds within a hydrophobic cleft on the peptide surface. This hydrophobic cleft is defined by the side chains of residues Val1, Phe4, Ile12, and Ala13. Backbone amide protons of Phe4 and Ala13 and the backbone carbonyl oxygen of Lys2 that lie within this cleft appear to form hydrogen bonds with the guanosine O6 and N1H atoms, respectively. In addition, the positively charged side chain of Arg14 is ideally positioned for electrostatic interactions with the phosphodiester backbone of the nucleic acid. The structural findings provide a rationalization for the general conservation of these hydrophobic and basic residues in CCHC zinc fingers, and are consistent with site-directed mutagenesis results that implicate these residues as direct participants in viral genome recognition.

  12. Los Alamos Space Weather Summer School

    NASA Astrophysics Data System (ADS)

    Koller, J.

    2011-12-01

    Los Alamos National Lab recently initiated a new summer school specializing on space science, space weather, and instrumentation. The school is geared towards graduate level students and has been established to bring graduate students together with internationally recognized scientists at the Los Alamos National Lab. Students are receiving a prestigious Vela Fellowship to cover relocation expenses and cost of living for the duration of their stay in Los Alamos. For two months students have the opportunity to attend science lectures given by distinguished researchers at LANL. Topics are related to space weather research including plasma physics, radiation belts, numerical modeling, solar wind physics, spacecraft charging, and instrumentation. Students are also working closely with a Los Alamos mentor on exciting space weather science topics with access to Los Alamos GPS and geosynchronous data. The summer school concludes with project presentations by the students in a technical forum. The program is designed for graduate students currently enrolled at US Universities and open to all nationalities. We are presenting an overview of this exciting new program funded by IGPP (Institute of Geophysics and Planetary Physics), the Global Security Directorate, and the Directorate for Science, Technology and Engineering at Los Alamos National Lab.

  13. Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G. The WHO and NIAID Networks for HIV Isolation and Characterization.

    PubMed Central

    Gao, F; Morrison, S G; Robertson, D L; Thornton, C L; Craig, S; Karlsson, G; Sodroski, J; Morgado, M; Galvao-Castro, B; von Briesen, H

    1996-01-01

    Present knowledge of human immunodeficiency virus type 1 (HIV-1) envelope immunobiology has been derived almost exclusively from analyses of subtype B viruses, yet such viruses represent only a minority of strains currently spreading worldwide. To generate a more representative panel of genetically diverse envelope genes, we PCR amplified, cloned, and sequenced complete gp160 coding regions of 35 primary (peripheral blood mononuclear cell-propagated) HIV-1 isolates collected at major epicenters of the current AIDS pandemic. Analysis of their deduced amino acid sequences revealed several important differences from prototypic subtype B strains, including changes in the number and distribution of cysteine residues, substantial length differences in hypervariable regions, and premature truncations in the gp41 domain. Moreover, transiently expressed glycoprotein precursor molecules varied considerably in both size and carbohydrate content. Phylogenetic analyses of full-length env sequences indicated that the panel included members of all major sequence subtypes of HIV-1 group M (clades A to G), as well as an intersubtype recombinant (F/B) from an infected individual in Brazil. In addition, all subtype E and three subtype G viruses initially classified on the basis of partial env sequences were found to cluster in subtype A in the 3' half of their gp41 coding region, suggesting that they are also recombinant. The biological activity of PCR-derived env genes was examined in a single-round virus infectivity assay. This analysis identified 20 clones, including 1 from each subtype (or recombinant), which expressed fully functional envelope glycoproteins. One of these, derived from a patient with rapid CD4 cell decline, contained an amino acid substitution in a highly conserved endocytosis signal (Y721C), as mediated virus entry with very poor efficiency, although they did not contain sequence changes predicted to alter protein function. These results indicate that the env

  14. Los Alamos Laser Eye Investigation.

    SciTech Connect

    Odom, C. R.

    2005-01-01

    A student working in a laser laboratory at Los Alamos National Laboratory sustained a serious retinal injury to her left eye when she attempted to view suspended particles in a partially evacuated target chamber. The principle investigator was using the white light from the flash lamp of a Class 4 Nd:YAG laser to illuminate the particles. Since the Q-switch was thought to be disabled at the time of the accident, the principal investigator assumed it would be safe to view the particles without wearing laser eye protection. The Laboratory Director appointed a team to investigate the accident and to report back to him the events and conditions leading up to the accident, equipment malfunctions, safety management causal factors, supervisory and management action/inaction, adequacy of institutional processes and procedures, emergency and notification response, effectiveness of corrective actions and lessons learned from previous similar events, and recommendations for human and institutional safety improvements. The team interviewed personnel, reviewed documents, and characterized systems and conditions in the laser laboratory during an intense six week investigation. The team determined that the direct and primary failures leading to this accident were, respectively, the principle investigator's unsafe work practices and the institution's inadequate monitoring of worker performance. This paper describes the details of the investigation, the human and institutional failures, and the recommendations for improving the laser safety program.

  15. Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa

    PubMed Central

    Jimenez Cruz, Camilo A.; Garcia-Beltran, Wilfredo F.; Carlson, Jonathan M.; van Teijlingen, Nienke H.; Mann, Jaclyn K.; Jaggernath, Manjeetha; Kang, Seung-gu; Körner, Christian; Chung, Amy W.; Schafer, Jamie L.; Evans, David T.; Alter, Galit; Walker, Bruce D.; Goulder, Philip J.; Carrington, Mary; Hartmann, Pia; Pertel, Thomas; Zhou, Ruhong; Ndung’u, Thumbi; Altfeld, Marcus

    2015-01-01

    Background Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure. Methods and Findings Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+ NK cells through sequence variations within HLA class I—presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 ± 10.45 standard deviation [SD] and variant mean 44.67 ± 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 ± 0.07 standard error of the mean [SEM] and variant mean 0.63 ± 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control. Conclusions These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades

  16. Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon

    PubMed Central

    2011-01-01

    Background The HIV epidemic in Cameroon is characterized by a high degree of viral genetic diversity with circulating recombinant forms (CRFs) being predominant. The goal of our study was to determine recent trends in virus evolution and emergence of drug resistance in blood donors and HIV positive patients. Methodology Blood specimens of 73 individuals were collected from three cities and a few villages in Cameroon and viruses were isolated by co-cultivation with PBMCs. Nested PCR was performed for gag p17 (670 bp) pol (840 bp) and Env gp41 (461 bp) genes. Sequences were phylogenetically analyzed using a reference set of sequences from the Los Alamos database. Results Phylogenetic analysis based on partial sequences revealed that 65% (n = 48) of strains were CRF02_AG, 4% (n = 3) subtype F2, 1% each belonged to CRF06 (n = 1), CRF11 (n = 1), subtype G (n = 1), subtype D (n = 1), CRF22_01A1 (n = 1), and 26% (n = 18) were Unique Recombinant Forms (URFs). Most URFs contained CRF02_AG in one or two HIV gene fragments analyzed. Furthermore, pol sequences of 61 viruses revealed drug resistance in 55.5% of patients on therapy and 44% of drug naïve individuals in the RT and protease regions. Overall URFs that had a primary HIV subtype designation in the pol region showed higher HIV-1 p24 levels than other recombinant forms in cell culture based replication kinetics studies. Conclusions Our results indicate that although CRF02_AG continues to be the predominant strain in Cameroon, phylogenetically the HIV epidemic is continuing to evolve as multiple recombinants of CRF02_AG and URFs were identified in the individuals studied. CRF02_AG recombinants that contained the pol region of a primary subtype showed higher replicative advantage than other variants. Identification of drug resistant strains in drug-naïve patients suggests that these viruses are being transmitted in the population studied. Our findings support the need for continued molecular surveillance in this region

  17. Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

    SciTech Connect

    Liu, Donglai; Zuo, Tao; Hora, Bhavna; Song, Hongshuo; Kong, Wei; Yu, Xianghui; Goonetilleke, Nilu; Bhattacharya, Tanmoy; Perelson, Alan S.; Haynes, Barton F.; McMichael, Andrew J.; Gao, Feng

    2014-01-01

    Background: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. Results: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, the fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. Conclusions: Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.

  18. Preexisting compensatory amino acids compromise fitness costs of a HIV-1 T cell escape mutation

    DOE PAGES

    Liu, Donglai; Zuo, Tao; Hora, Bhavna; Song, Hongshuo; Kong, Wei; Yu, Xianghui; Goonetilleke, Nilu; Bhattacharya, Tanmoy; Perelson, Alan S.; Haynes, Barton F.; et al

    2014-01-01

    Background: Fitness costs and slower disease progression are associated with a cytolytic T lymphocyte (CTL) escape mutation T242N in Gag in HIV-1-infected individuals carrying HLA-B*57/5801 alleles. However, the impact of different context in diverse HIV-1 strains on the fitness costs due to the T242N mutation has not been well characterized. To better understand the extent of fitness costs of the T242N mutation and the repair of fitness loss through compensatory amino acids, we investigated its fitness impact in different transmitted/founder (T/F) viruses. Results: The T242N mutation resulted in various levels of fitness loss in four different T/F viruses. However, themore » fitness costs were significantly compromised by preexisting compensatory amino acids in (Isoleucine at position 247) or outside (glutamine at position 219) the CTL epitope. Moreover, the transmitted T242N escape mutant in subject CH131 was as fit as the revertant N242T mutant and the elimination of the compensatory amino acid I247 in the T/F viral genome resulted in significant fitness cost, suggesting the fitness loss caused by the T242N mutation had been fully repaired in the donor at transmission. Analysis of the global circulating HIV-1 sequences in the Los Alamos HIV Sequence Database showed a high prevalence of compensatory amino acids for the T242N mutation and other T cell escape mutations. Conclusions: Our results show that the preexisting compensatory amino acids in the majority of circulating HIV-1 strains could significantly compromise the fitness loss due to CTL escape mutations and thus increase challenges for T cell based vaccines.« less

  19. HIV-1 transmission linkage in an HIV-1 prevention clinical trial

    SciTech Connect

    Leitner, Thomas; Campbell, Mary S; Mullins, James I; Hughes, James P; Wong, Kim G; Raugi, Dana N; Scrensen, Stefanie

    2009-01-01

    HIV-1 sequencing has been used extensively in epidemiologic and forensic studies to investigate patterns of HIV-1 transmission. However, the criteria for establishing genetic linkage between HIV-1 strains in HIV-1 prevention trials have not been formalized. The Partners in Prevention HSV/HIV Transmission Study (ClinicaITrials.gov NCT00194519) enrolled 3408 HIV-1 serodiscordant heterosexual African couples to determine the efficacy of genital herpes suppression with acyclovir in reducing HIV-1 transmission. The trial analysis required laboratory confirmation of HIV-1 linkage between enrolled partners in couples in which seroconversion occurred. Here we describe the process and results from HIV-1 sequencing studies used to perform transmission linkage determination in this clinical trial. Consensus Sanger sequencing of env (C2-V3-C3) and gag (p17-p24) genes was performed on plasma HIV-1 RNA from both partners within 3 months of seroconversion; env single molecule or pyrosequencing was also performed in some cases. For linkage, we required monophyletic clustering between HIV-1 sequences in the transmitting and seroconverting partners, and developed a Bayesian algorithm using genetic distances to evaluate the posterior probability of linkage of participants sequences. Adjudicators classified transmissions as linked, unlinked, or indeterminate. Among 151 seroconversion events, we found 108 (71.5%) linked, 40 (26.5%) unlinked, and 3 (2.0%) to have indeterminate transmissions. Nine (8.3%) were linked by consensus gag sequencing only and 8 (7.4%) required deep sequencing of env. In this first use of HIV-1 sequencing to establish endpoints in a large clinical trial, more than one-fourth of transmissions were unlinked to the enrolled partner, illustrating the relevance of these methods in the design of future HIV-1 prevention trials in serodiscordant couples. A hierarchy of sequencing techniques, analysis methods, and expert adjudication contributed to the linkage

  20. Status of Monte Carlo at Los Alamos

    SciTech Connect

    Thompson, W.L.; Cashwell, E.D.

    1980-01-01

    At Los Alamos the early work of Fermi, von Neumann, and Ulam has been developed and supplemented by many followers, notably Cashwell and Everett, and the main product today is the continuous-energy, general-purpose, generalized-geometry, time-dependent, coupled neutron-photon transport code called MCNP. The Los Alamos Monte Carlo research and development effort is concentrated in Group X-6. MCNP treats an arbitrary three-dimensional configuration of arbitrary materials in geometric cells bounded by first- and second-degree surfaces and some fourth-degree surfaces (elliptical tori). Monte Carlo has evolved into perhaps the main method for radiation transport calculations at Los Alamos. MCNP is used in every technical division at the Laboratory by over 130 users about 600 times a month accounting for nearly 200 hours of CDC-7600 time.

  1. New Generation of Los Alamos Opacity Tables

    NASA Astrophysics Data System (ADS)

    Colgan, James; Kilcrease, D. P.; Magee, N. H.; Sherrill, M. E.; Abdallah, J.; Hakel, P.; Fontes, C. J.; Guzik, J. A.; Mussack, K. A.

    2016-05-01

    We present a new generation of Los Alamos OPLIB opacity tables that have been computed using the ATOMIC code. Our tables have been calculated for all 30 elements from hydrogen through zinc and are publicly available through our website. In this poster we discuss the details of the calculations that underpin the new opacity tables. We also show several recent applications of the use of our opacity tables to solar modeling and other astrophysical applications. In particular, we demonstrate that use of the new opacities improves the agreement between solar models and helioseismology, but does not fully resolve the long-standing `solar abundance' problem. The Los Alamos National Laboratory is operated by Los Alamos National Security, LLC for the National Nuclear Security Administration of the U.S. Department of Energy under Contract No. DE-AC5206NA25396.

  2. Publications of Los Alamos Research, 1983

    SciTech Connect

    Sheridan, C.J.; McClary, W.J.; Rich, J.A.; Rodriguez, L.L.

    1984-10-01

    This bibliography is a compilation of unclassified publications of work done at the Los Alamos National Laboratory for 1983. Papers published in 1982 are included regardless of when they were actually written. Publications received too late for inclusion in earlier compilations have also been listed. Declassification of previously classified reports is considered to constitute publication. All classified issuances are omitted - even those papers, themselves unclassified, which were published only as part of a classified document. If a paper was published more than once, all places of publication are included. The bibliography includes Los Alamos National Laboratory reports, papers released as non-Laboratory reports, journal articles, books, chapters of books, conference papers either published separately or as part of conference proceedings issued as books or reports, papers publishd in congressional hearings, theses, and US patents. Publications by Los Alamos authors that are not records of Laboratory-sponsored work are included when the Library becomes aware of them.

  3. Publications of Los Alamos research 1980

    SciTech Connect

    Salazar, C.A.; Willis, J.K.

    1981-09-01

    This bibliography is a compilation of unclassified publications of work done at the Los Alamos National Laboratory for 1980. Papers published in 1980 are included regardless of when they were actually written. Publications received too late for inclusion in earlier compilations have also been listed. Declassification of previously classified reports is considered to constitute publication. All classified issuances are omitted-even those papers, themselves unclassified, which were published only as part of a classified document. If a paper was pubished more than once, all places of publication are included. The bibliography includes Los Alamos National Laboratory reports, papers released as non-laboratory reports, journal articles, books, chapters of books, conference papers published either separately or as part of conference proceedings issued as books or reports, papers published in congressional hearings, theses, and US patents. Publications by Los Alamos authors that are not records of Laboratory-sponsored work are included when the Library becomes aware of them.

  4. Nonlinear analysis of biological sequences

    SciTech Connect

    Torney, D.C.; Bruno, W.; Detours, V.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The main objectives of this project involved deriving new capabilities for analyzing biological sequences. The authors focused on tabulating the statistical properties exhibited by Human coding DNA sequences and on techniques of inferring the phylogenetic relationships among protein sequences related by descent.

  5. Dispersion of the HIV-1 Epidemic in Men Who Have Sex with Men in the Netherlands: A Combined Mathematical Model and Phylogenetic Analysis

    PubMed Central

    Ratmann, Oliver; van Sighem, Ard; Hermanides, Hillegonda S.; Dutilh, Bas E.; Gras, Luuk; Rodrigues Faria, Nuno; van den Hengel, Rob; Duits, Ashley J.; Reiss, Peter; de Wolf, Frank; Fraser, Christophe

    2015-01-01

    Background The HIV-1 subtype B epidemic amongst men who have sex with men (MSM) is resurgent in many countries despite the widespread use of effective combination antiretroviral therapy (cART). In this combined mathematical and phylogenetic study of observational data, we aimed to find out the extent to which the resurgent epidemic is the result of newly introduced strains or of growth of already circulating strains. Methods and Findings As of November 2011, the ATHENA observational HIV cohort of all patients in care in the Netherlands since 1996 included HIV-1 subtype B polymerase sequences from 5,852 patients. Patients who were diagnosed between 1981 and 1995 were included in the cohort if they were still alive in 1996. The ten most similar sequences to each ATHENA sequence were selected from the Los Alamos HIV Sequence Database, and a phylogenetic tree was created of a total of 8,320 sequences. Large transmission clusters that included ≥10 ATHENA sequences were selected, with a local support value ≥ 0.9 and median pairwise patristic distance below the fifth percentile of distances in the whole tree. Time-varying reproduction numbers of the large MSM-majority clusters were estimated through mathematical modeling. We identified 106 large transmission clusters, including 3,061 (52%) ATHENA and 652 Los Alamos sequences. Half of the HIV sequences from MSM registered in the cohort in the Netherlands (2,128 of 4,288) were included in 91 large MSM-majority clusters. Strikingly, at least 54 (59%) of these 91 MSM-majority clusters were already circulating before 1996, when cART was introduced, and have persisted to the present. Overall, 1,226 (35%) of the 3,460 diagnoses among MSM since 1996 were found in these 54 long-standing clusters. The reproduction numbers of all large MSM-majority clusters were around the epidemic threshold value of one over the whole study period. A tendency towards higher numbers was visible in recent years, especially in the more recently

  6. SEDs at Los Alamos: A Personal Memoir

    NASA Astrophysics Data System (ADS)

    Bederson, Benjamin

    2001-03-01

    I have written this personal memoir approximately 55 years after the events I describe. It is based almost exclusively on memory, since apart from the diary I kept while on Tinian, I have few documents concerning it. It covers my service in the U.S. Army's Special Engineering Detachment (SED) in Oak Ridge and Los Alamos in 1944-45, on Tinian island, the launching pad for the bombing raids on Japan, in the summer and fall of 1945, and my return to Los Alamos until my discharge in January 1946.

  7. Women and HIV

    MedlinePlus

    ... Consumer Information by Audience For Women Women and HIV Share Tweet Linkedin Pin it More sharing options ... HIV? What should pregnant women know about HIV? HIV Quick Facts What is HIV? HIV is the ...

  8. The C-terminal tail of the gp41 transmembrane envelope glycoprotein of HIV-1 clades A, B, C, and D may exist in two conformations: an analysis of sequence, structure, and function

    SciTech Connect

    Hollier, Mark J.; Dimmock, Nigel J. . E-mail: n.j.dimmock@warwick.ac.uk

    2005-07-05

    In addition to the major ectodomain, the gp41 transmembrane glycoprotein of HIV-1 is now known to have a minor ectodomain that is part of the long C-terminal tail. Both ectodomains are highly antigenic, carry neutralizing and non-neutralizing epitopes, and are involved in virus-mediated fusion activity. However, data have so far been biologically based, and derived solely from T cell line-adapted (TCLA), B clade viruses. Here we have carried out sequence and theoretically based structural analyses of 357 gp41 C-terminal sequences of mainly primary isolates of HIV-1 clades A, B, C, and D. Data show that all these viruses have the potential to form a tail loop structure (the minor ectodomain) supported by three, {beta}-sheet, membrane-spanning domains (MSDs). This means that the first (N-terminal) tyrosine-based sorting signal of the gp41 tail is situated outside the cell membrane and is non-functional, and that gp41 that reaches the cell surface may be recycled back into the cytoplasm through the activity of the second tyrosine-sorting signal. However, we suggest that only a minority of cell-associated gp41 molecules - those destined for incorporation into virions - has 3 MSDs and the minor ectodomain. Most intracellular gp41 has the conventional single MSD, no minor ectodomain, a functional first tyrosine-based sorting signal, and in line with current thinking is degraded intracellularly. The gp41 structural diversity suggested here can be viewed as an evolutionary strategy to minimize HIV-1 envelope glycoprotein expression on the cell surface, and hence possible cytotoxicity and immune attack on the infected cell.

  9. Induction inserts at the Los Alamos PSR

    SciTech Connect

    King-Yuen Ng

    2002-09-30

    Ferrite-loaded induction tuners installed in the Los Alamos Proton Storage Ring have been successful in compensating space-charge effects. However, the resistive part of the ferrite introduces unacceptable microwave instability and severe bunch lengthening. An effective cure was found by heating the ferrite cores up to {approx} 130 C. An understanding of the instability and cure is presented.

  10. Los Alamos waste drum shufflers users manual

    SciTech Connect

    Rinard, P.M.; Adams, E.L.; Painter, J.

    1993-08-24

    This user manual describes the Los Alamos waste drum shufflers. The primary purpose of the instruments is to assay the mass of {sup 235}U (or other fissile materials) in drums of assorted waste. It can perform passive assays for isotopes that spontaneously emit neutrons or active assays using the shuffler technique as described on this manual.

  11. Proceedings of the Los Alamos neutrino workshop

    SciTech Connect

    Boehm, F.; Stephenson, G.J. Jr.

    1982-08-01

    A workshop on neutrino physics was held at Los Alamos from June 8 to 12, 1981. The material presented has been provided in part by the organizers, in part by the chairmen of the working sessions. Closing date for contributions was October 1981.

  12. Los Alamos Fires From Landsat 7

    NASA Technical Reports Server (NTRS)

    2002-01-01

    On May 9, 2000, the Landsat 7 satellite acquired an image of the area around Los Alamos, New Mexico. The Landsat 7 satellite acquired this image from 427 miles in space through its sensor called the Enhanced Thematic Mapper Plus (ETM+). Evident within the imagery is a view of the ongoing Cerro Grande fire near the town of Los Alamos and the Los Alamos National Laboratory. Combining the high-resolution (30 meters per pixel in this scene) imaging capacity of ETM+ with its multi-spectral capabilities allows scientists to penetrate the smoke plume and see the structure of the fire on the surface. Notice the high-level of detail in the infrared image (bottom), in which burn scars are clearly distinguished from the hotter smoldering and flaming parts of the fire. Within this image pair several features are clearly visible, including the Cerro Grande fire and smoke plume, the town of Los Alamos, the Los Alamos National Laboratory and associated property, and Cerro Grande peak. Combining ETM+ channels 7, 4, and 2 (one visible and two infrared channels) results in a false color image where vegetation appears as bright to dark green (bottom image). Forested areas are generally dark green while herbaceous vegetation is light green. Rangeland or more open areas appear pink to light purple. Areas with extensive pavement or urban development appear light blue or white to purple. Less densely-developed residential areas appear light green and golf courses are very bright green. The areas recently burned appear black. Dark red to bright red patches, or linear features within the burned area, are the hottest and possibly actively burning areas of the fire. The fire is spreading downslope and the front of the fire is readily detectable about 2 kilometers to the west and south of Los Alamos. Combining ETM+ channels 3, 2, and 1 provides a true-color image of the greater Los Alamos region (top image). Vegetation is generally dark to medium green. Forested areas are very dark green

  13. Long-Range HIV Genotyping Using Viral RNA and Proviral DNA for Analysis of HIV Drug Resistance and HIV Clustering

    PubMed Central

    Novitsky, Vlad; Zahralban-Steele, Melissa; McLane, Mary Fran; Moyo, Sikhulile; van Widenfelt, Erik; Gaseitsiwe, Simani; Makhema, Joseph

    2015-01-01

    The goal of the study was to improve the methodology of HIV genotyping for analysis of HIV drug resistance and HIV clustering. Using the protocol of Gall et al. (A. Gall, B. Ferns, C. Morris, S. Watson, M. Cotten, M. Robinson, N. Berry, D. Pillay, and P. Kellam, J Clin Microbiol 50:3838–3844, 2012, doi:10.1128/JCM.01516-12), we developed a robust methodology for amplification of two large fragments of viral genome covering about 80% of the unique HIV-1 genome sequence. Importantly, this method can be applied to both viral RNA and proviral DNA amplification templates, allowing genotyping in HIV-infected subjects with suppressed viral loads (e.g., subjects on antiretroviral therapy [ART]). The two amplicons cover critical regions across the HIV-1 genome (including pol and env), allowing analysis of mutations associated with resistance to protease inhibitors, reverse transcriptase inhibitors (nucleoside reverse transcriptase inhibitors [NRTIs] and nonnucleoside reverse transcriptase inhibitors [NNRTIs]), integrase strand transfer inhibitors, and virus entry inhibitors. The two amplicons generated span 7,124 bp, providing substantial sequence length and numbers of informative sites for comprehensive phylogenic analysis and greater refinement of viral linkage analyses in HIV prevention studies. The long-range HIV genotyping from proviral DNA was successful in about 90% of 212 targeted blood specimens collected in a cohort where the majority of patients had suppressed viral loads, including 65% of patients with undetectable levels of HIV-1 RNA loads. The generated amplicons could be sequenced by different methods, such as population Sanger sequencing, single-genome sequencing, or next-generation ultradeep sequencing. The developed method is cost-effective—the cost of the long-range HIV genotyping is under $140 per subject (by Sanger sequencing)—and has the potential to enable the scale up of public health HIV prevention interventions. PMID:26041893

  14. Long-Range HIV Genotyping Using Viral RNA and Proviral DNA for Analysis of HIV Drug Resistance and HIV Clustering.

    PubMed

    Novitsky, Vlad; Zahralban-Steele, Melissa; McLane, Mary Fran; Moyo, Sikhulile; van Widenfelt, Erik; Gaseitsiwe, Simani; Makhema, Joseph; Essex, M

    2015-08-01

    The goal of the study was to improve the methodology of HIV genotyping for analysis of HIV drug resistance and HIV clustering. Using the protocol of Gall et al. (A. Gall, B. Ferns, C. Morris, S. Watson, M. Cotten, M. Robinson, N. Berry, D. Pillay, and P. Kellam, J Clin Microbiol 50:3838-3844, 2012, doi:10.1128/JCM.01516-12), we developed a robust methodology for amplification of two large fragments of viral genome covering about 80% of the unique HIV-1 genome sequence. Importantly, this method can be applied to both viral RNA and proviral DNA amplification templates, allowing genotyping in HIV-infected subjects with suppressed viral loads (e.g., subjects on antiretroviral therapy [ART]). The two amplicons cover critical regions across the HIV-1 genome (including pol and env), allowing analysis of mutations associated with resistance to protease inhibitors, reverse transcriptase inhibitors (nucleoside reverse transcriptase inhibitors [NRTIs] and nonnucleoside reverse transcriptase inhibitors [NNRTIs]), integrase strand transfer inhibitors, and virus entry inhibitors. The two amplicons generated span 7,124 bp, providing substantial sequence length and numbers of informative sites for comprehensive phylogenic analysis and greater refinement of viral linkage analyses in HIV prevention studies. The long-range HIV genotyping from proviral DNA was successful in about 90% of 212 targeted blood specimens collected in a cohort where the majority of patients had suppressed viral loads, including 65% of patients with undetectable levels of HIV-1 RNA loads. The generated amplicons could be sequenced by different methods, such as population Sanger sequencing, single-genome sequencing, or next-generation ultradeep sequencing. The developed method is cost-effective-the cost of the long-range HIV genotyping is under $140 per subject (by Sanger sequencing)-and has the potential to enable the scale up of public health HIV prevention interventions. PMID:26041893

  15. Nuclear Forensics at Los Alamos National Laboratory

    SciTech Connect

    Podlesak, David W; Steiner, Robert E.; Burns, Carol J.; LaMont, Stephen P.; Tandon, Lav

    2012-08-09

    The overview of this presentation is: (1) Introduction to nonproliferation efforts; (2) Scope of activities at Los Alamos National Laboratory; (3) Facilities for radioanalytical work at LANL; (4) Radiochemical characterization capabilities; and (5) Bulk chemical and materials analysis capabilities. Some conclusions are: (1) Analytical chemistry measurements on plutonium and uranium matrices are critical to numerous defense and non-defense programs including safeguards accountancy verification measurements; (2) Los Alamos National Laboratory operates capable actinide analytical chemistry and material science laboratories suitable for nuclear material forensic characterization; (3) Actinide analytical chemistry uses numerous means to validate and independently verify that measurement data quality objectives are met; and (4) Numerous LANL nuclear facilities support the nuclear material handling, preparation, and analysis capabilities necessary to evaluate samples containing nearly any mass of an actinide (attogram to kilogram levels).

  16. Water Supply at Los Alamos during 1997

    SciTech Connect

    M. N. Maes; S. G. McLin; W. D. Purtymun

    1998-12-01

    Production of potable municipal water supplies during 1997 totaled about 1,285.9 million gallons from wells in the Guaje, Pajarito, and Otowi well fields. There was no water used from the spring gallery in Water Canyon or from Guaje Reservoir during 1997. About 2.4 million gallons of water from Los Alamos Reservoir was used to irrigate public parks and recreational lands. The total water usage in 1997 was about 1,288.3 million gallons, or about 135 gallons per day per person living in Los Alamos County. Groundwater pumpage was down about 82.2 million gallons in 1997 compared with the pumpage in 1996. Four new replacement wells were drilled and cased in Guaje Canyon between October 1997 and March 1998. These wells are currently being developed and aquifer tests are being performed. A special report summarizing the geological, geophysical, and well construction logs will be issued in the near future for these new wells.

  17. Los Alamos Team Demonstrates Bottle Scanner Technology

    ScienceCinema

    Espy, Michelle; Schultz, Larry

    2016-07-12

    Los Alamos scientists are demonstrating a Nuclear Magnetic Resonance Imaging (NMR) technology that may provide a breakthrough for screening liquids at airport security. By adding low-power X-ray data to the NMR mix, scientists believe they have unlocked a new detection technology. Funded in part by the Department of Homeland Security's Science and Technology Directorate, the new technology is called MagRay.

  18. Status of the Los Alamos Anger camera

    SciTech Connect

    Seeger, P.A.; Nutter, M.J.

    1985-01-01

    Results of preliminary tests of the neutron Anger camera being developed at Los Alamos are presented. This detector uses a unique encoding scheme involving parellel processing of multiple receptive fields. Design goals have not yet been met, but the results are very encouraging and improvements in the test procedures are expected to show that the detector will be ready for use on a small-angle scattering instrument next year. 3 refs., 4 figs.

  19. Los Alamos synchronous orbit data set

    SciTech Connect

    Baker, D.N.; Higbie, P.R.; Belian, R.D.; Hones, E.W.; Klebesadel, R.W.

    1981-01-01

    Energetic electron (30-15000 keV) and proton 145 keV to 150 MeV) measurements made by Los Alamos National Laboratory sensors at geostationary orbit (6.6 R/sub E/) are summarized. The instrumentation employed and the satellite positions are described. The spacecraft have been variously located, but in their present configuration the Los Alamos satellites designated 1976-059, 1977-007, and 1979-053 are located, respectively, at approx. 70/sup 0/W, approx. 70/sup 0/E, and approx. 135/sup 0/W longitude. Several examples of the high temporal and full three-dimensional spatial measurement capabilities of these instruments are illustrated by examples from the published literature. Discussion is also given for the Los Alamos Synoptic Data Set (SDS) which gives a broad overview of the Los Alamos geostationary orbit measurements. The SDS data are plotted in terms of daily average spectra, 3-hour local time averages, and in a variety of statistical formats. The data summarize conditions from mid-1976 through 1978 (S/C 1976-059) and from early 1977 through 1978 (S/C 1977-007). The SDS compilations presented correspond to measurements at 35/sup 0/W, 70/sup 0/W, and 135/sup 0/W geographic longitude and thus are indicative of conditions at 9/sup 0/, 11/sup 0/, and 4.8/sup 0/ geomagnetic latitude, respectively. The bulk of the SDS report presents data plots which are organized according to Carrington solar rotations and, as such, the data are readily comparable to solar rotation-dependent interplanetary conditions. Potential applications of the Synoptic Data Set (available to all interested users in June 1981) are discussed.

  20. Amphibians and Reptiles of Los Alamos County

    SciTech Connect

    Teralene S. Foxx; Timothy K. Haarmann; David C. Keller

    1999-10-01

    Recent studies have shown that amphibians and reptiles are good indicators of environmental health. They live in terrestrial and aquatic environments and are often the first animals to be affected by environmental change. This publication provides baseline information about amphibians and reptiles that are present on the Pajarito Plateau. Ten years of data collection and observations by researchers at Los Alamos National Laboratory, the University of New Mexico, the New Mexico Department of Game and Fish, and hobbyists are represented.

  1. Los Alamos Team Demonstrates Bottle Scanner Technology

    SciTech Connect

    Espy, Michelle; Schultz, Larry

    2014-05-06

    Los Alamos scientists are demonstrating a Nuclear Magnetic Resonance Imaging (NMR) technology that may provide a breakthrough for screening liquids at airport security. By adding low-power X-ray data to the NMR mix, scientists believe they have unlocked a new detection technology. Funded in part by the Department of Homeland Security's Science and Technology Directorate, the new technology is called MagRay.

  2. The Los Alamos accelerator code group

    SciTech Connect

    Krawczyk, F.L.; Billen, J.H.; Ryne, R.D.; Takeda, Harunori; Young, L.M.

    1995-05-01

    The Los Alamos Accelerator Code Group (LAACG) is a national resource for members of the accelerator community who use and/or develop software for the design and analysis of particle accelerators, beam transport systems, light sources, storage rings, and components of these systems. Below the authors describe the LAACG`s activities in high performance computing, maintenance and enhancement of POISSON/SUPERFISH and related codes and the dissemination of information on the INTERNET.

  3. Los Alamos Novel Rocket Design Flight Tested

    SciTech Connect

    Tappan, Bryce

    2014-10-23

    Los Alamos National Laboratory scientists recently flight tested a new rocket design that includes a high-energy fuel and a motor design that also delivers a high degree of safety. Researchers will now work to scale-up the design, as well as explore miniaturization of the system, in order to exploit all potential applications that would require high-energy, high-velocity, and correspondingly high safety margins.

  4. Los Alamos Novel Rocket Design Flight Tested

    ScienceCinema

    Tappan, Bryce

    2016-07-12

    Los Alamos National Laboratory scientists recently flight tested a new rocket design that includes a high-energy fuel and a motor design that also delivers a high degree of safety. Researchers will now work to scale-up the design, as well as explore miniaturization of the system, in order to exploit all potential applications that would require high-energy, high-velocity, and correspondingly high safety margins.

  5. Los Alamos National Laboratory Facility Review

    SciTech Connect

    Nelson, Ronald Owen

    2015-06-05

    This series of slides depicts the Los Alamos Neutron Science Center (LANSCE). The Center's 800-MeV linac produces H+ and H- beams as well as beams of moderated (cold to 1 MeV) and unmoderated (0.1 to 600 MeV) neutrons. Experimental facilities and their capabilities and characteristics are outlined. Among these are LENZ, SPIDER, and DANCE.

  6. Spatio-Temporal History of HIV-1 CRF35_AD in Afghanistan and Iran

    PubMed Central

    Eybpoosh, Sana; Bahrampour, Abbas; Karamouzian, Mohammad; Azadmanesh, Kayhan; Jahanbakhsh, Fatemeh; Mostafavi, Ehsan; Zolala, Farzaneh; Haghdoost, Ali Akbar

    2016-01-01

    HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD) has an important position in the epidemiological profile of Afghanistan and Iran. Despite the presence of this clade in Afghanistan and Iran for over a decade, our understanding of its origin and dissemination patterns is limited. In this study, we performed a Bayesian phylogeographic analysis to reconstruct the spatio-temporal dispersion pattern of this clade using eligible CRF35_AD gag and pol sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_AD-like pol sequence available from USA). Bayesian Markov Chain Monte Carlo algorithm was implemented in BEAST v1.8.1. Between-country dispersion rates were tested with Bayesian stochastic search variable selection method and were considered significant where Bayes factor values were greater than three. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.7). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersion of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting it not to be a true CRF35_AD lineage. Potential factors contributing to viral exchange between Afghanistan and Iran could be injection drug

  7. Spatio-Temporal History of HIV-1 CRF35_AD in Afghanistan and Iran.

    PubMed

    Eybpoosh, Sana; Bahrampour, Abbas; Karamouzian, Mohammad; Azadmanesh, Kayhan; Jahanbakhsh, Fatemeh; Mostafavi, Ehsan; Zolala, Farzaneh; Haghdoost, Ali Akbar

    2016-01-01

    HIV-1 Circulating Recombinant Form 35_AD (CRF35_AD) has an important position in the epidemiological profile of Afghanistan and Iran. Despite the presence of this clade in Afghanistan and Iran for over a decade, our understanding of its origin and dissemination patterns is limited. In this study, we performed a Bayesian phylogeographic analysis to reconstruct the spatio-temporal dispersion pattern of this clade using eligible CRF35_AD gag and pol sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_AD-like pol sequence available from USA). Bayesian Markov Chain Monte Carlo algorithm was implemented in BEAST v1.8.1. Between-country dispersion rates were tested with Bayesian stochastic search variable selection method and were considered significant where Bayes factor values were greater than three. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.7). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersion of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting it not to be a true CRF35_AD lineage. Potential factors contributing to viral exchange between Afghanistan and Iran could be injection drug

  8. Critical partnerships: Los Alamos, universities, and industry

    SciTech Connect

    Berger, C.L.

    1997-04-01

    Los Alamos National Laboratory, situated 35 miles northwest of Santa Fe, NM, is one of the Department of Energy`s three Defense Programs laboratories. It encompasses 43 square miles, employees approximately 10,000 people, and has a budget of approximately $1.1B in FY97. Los Alamos has a strong post-cold war mission, that of reducing the nuclear danger. But even with that key role in maintaining the nation`s security, Los Alamos views partnerships with universities and industry as critical to its future well being. Why is that? As the federal budget for R&D comes under continued scrutiny and certain reduction, we believe that the triad of science and technology contributors to the national system of R&D must rely on and leverage each others capabilities. For us this means that we will rely on these partners to help us in 5 key ways: We expect that partnerships will help us maintain and enhance our core competencies. In doing so, we will be able to attract the best scientists and engineers. To keep on the cutting edge of research and development, we have found that partnerships maintain the excellence of staff through new and exciting challenges. Additionally, we find that from our university and corporate partners we often learn and incorporate {open_quotes}best practices{close_quotes} in organizational management and operations. Finally, we believe that a strong national system of R&D will ensure and enhance our ability to generate revenues.

  9. Exploration geochemistry: The Los Alamos experience

    SciTech Connect

    Maassen, L.W.; Bolivar, S.L.

    1989-01-01

    Los Alamos National Laboratory became actively involved in geochemical exploration in 1975 by conducting a reconnaissance-scale exploration program for uranium as part of the National Uranium Resource Evaluation program. Initially, only uranium and thorium were analyzed. By 1979 Los Alamos was analyzing a multielement suite. The data were presented in histograms and as black and white concentration plots for uranium and thorium only. Data for the remaining elements were presented as hard copy data listings in an appendix to the report. In 1983 Los Alamos began using exploration geochemistry for the purpose of finding economic mineral deposits to help stimulate the economies of underdeveloped countries. Stream-sediment samples were collected on the Caribbean island of St. Lucia and a geochemical atlas of that island was produced. The data were statistically smoothed and presented as computer-generated color plots of each element of the multielement suite. Studies for the US Bureau of Land Management in 1984 consisted of development of techniques for the integration of several large data sets, which could then be used for computer-assisted mineral resource assessments. A supervised classification technique was developed which compares the attributes of grid cells containing mines or mineral occurrences with attributes of unclassified cells not known to contain mines or occurrences. Color maps indicate how closely unclassified cells match in attributes the cells with mines or occurrences. 20 refs., 1 fig., 1 tab.

  10. Los Alamos National Laboratory building cost index

    SciTech Connect

    Orr, H.D.; Lemon, G.D.

    1982-10-01

    The Los Alamos National Laboratory Building Cost Index indicates that actual escalation since 1970 is near 10% per year. Therefore, the Laboratory will continue using a 10% per year escalation rate for construction estimates through 1985 and a slightly lower rate of 8% per year from 1986 through 1990. The computerized program compares the different elements involved in the cost of a typical construction project, which for our purposes, is a complex of office buildings and experimental laboratories. The input data used in the program consist primarily of labor costs and material and equipment costs. The labor costs are the contractual rates of the crafts workers in the Los Alamos area. For the analysis, 12 field-labor craft categories are used; each is weighted corresponding to the labor craft distribution associated with the typical construction project. The materials costs are current Los Alamos prices. Additional information sources include material and equipment quotes obtained through conversations with vendors and from trade publications. The material and equipment items separate into 17 categories for the analysis and are weighted corresponding to the material and equipment distribution associated with the typical construction project. The building cost index is compared to other national building cost indexes.

  11. Los Alamos National Laboratory Building Cost Index

    SciTech Connect

    Orr, H.D.; Lemon, G.D.

    1983-01-01

    The Los Alamos National Laboratory Building Cost Index indicates that actual escalation since 1970 is near 10% per year. Therefore, the Laboratory will continue using a 10% per year escalation rate for construction estimates through 1985 and a slightly lower rate of 8% per year from 1986 through 1990. The computerized program compares the different elements involved in the cost of a typical construction project, which for our purposes, is a complex of office buildings and experimental laboratores. The input data used in the program consist primarily of labor costs and material and equipment costs. The labor costs are the contractural rates of the crafts workers in the Los Alamos area. For the analysis, 12 field-labor draft categories are used; each is weighted corresponding to the labor craft distribution associated with the typical construction project. The materials costs are current Los Alamos prices. Additional information sources include material and equipment quotes obtained through conversations with vendors and from trade publications. The material and equipment items separate into 17 categories for the analysis and are weighted corresponding to the material and equipment distribution associated with the typical construction project. The building cost index is compared to other national building cost indexes.

  12. Get Tested for HIV

    MedlinePlus

    ... Print This Topic En español Get Tested for HIV Browse Sections The Basics Overview What Is HIV? ... 1 of 7 sections The Basics: What Is HIV? What is HIV? HIV stands for human immunodeficiency ...

  13. HIV Treatment: The Basics

    MedlinePlus

    HIV Treatment HIV Treatment: The Basics (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Antiretroviral therapy (ART) ... reduces the risk of HIV transmission . How do HIV medicines work? HIV attacks and destroys the infection- ...

  14. DETERMINISTIC TRANSPORT METHODS AND CODES AT LOS ALAMOS

    SciTech Connect

    J. E. MOREL

    1999-06-01

    The purposes of this paper are to: Present a brief history of deterministic transport methods development at Los Alamos National Laboratory from the 1950's to the present; Discuss the current status and capabilities of deterministic transport codes at Los Alamos; and Discuss future transport needs and possible future research directions. Our discussion of methods research necessarily includes only a small fraction of the total research actually done. The works that have been included represent a very subjective choice on the part of the author that was strongly influenced by his personal knowledge and experience. The remainder of this paper is organized in four sections: the first relates to deterministic methods research performed at Los Alamos, the second relates to production codes developed at Los Alamos, the third relates to the current status of transport codes at Los Alamos, and the fourth relates to future research directions at Los Alamos.

  15. HIV chemotherapy

    NASA Astrophysics Data System (ADS)

    Richman, Douglas D.

    2001-04-01

    The use of chemotherapy to suppress replication of the human immunodeficiency virus (HIV) has transformed the face of AIDS in the developed world. Pronounced reductions in illness and death have been achieved and healthcare utilization has diminished. HIV therapy has also provided many new insights into the pathogenesis and the viral and cellular dynamics of HIV infection. But challenges remain. Treatment does not suppress HIV replication in all patients, and the emergence of drug-resistant virus hinders subsequent treatment. Chronic therapy can also result in toxicity. These challenges prompt the search for new drugs and new therapeutic strategies to control chronic viral replication.

  16. Los Alamos Before and After the Fire

    NASA Technical Reports Server (NTRS)

    2002-01-01

    On May 4, 2000, a prescribed fire was set at Bandelier National Monument, New Mexico, to clear brush and dead and dying undergrowth to prevent a larger, subsequent wildfire. Unfortunately, due to high winds and extremely dry conditions in the surrounding area, the prescribed fire quickly raged out of control and, by May 10, the blaze had spread into the nearby town of Los Alamos. In all, more than 20,000 people were evacuated from their homes and more than 200 houses were destroyed as the flames consumed about 48,000 acres in and around the Los Alamos area. The pair of images above were acquired by the Enhanced Thematic Mapper Plus (ETM+) sensor, flying aboard NASA's Landsat 7 satellite, shortly before the Los Alamos fire (top image, acquired April 14) and shortly after the fire was extinguished (lower image, June 17). The images reveal the extent of the damage caused by the fire. Combining ETM+ channels 7, 4, and 2 (one visible and two infrared channels) results in a false-color image where vegetation appears as bright to dark green. Forested areas are generally dark green while herbaceous vegetation is light green. Rangeland or more open areas appear pink to light purple. Areas with extensive pavement or urban development appear light blue or white to purple. Less densely-developed residential areas appear light green and golf courses are very bright green. In the lower image, the areas recently burned appear bright red. Landsat 7 data courtesy United States Geological Survey EROS DataCenter. Images by Robert Simmon, NASA GSFC.

  17. Biological assessment for the effluent reduction program, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    Cross, S.P.

    1996-08-01

    This report describes the biological assessment for the effluent recution program proposed to occur within the boundaries of Los Alamos National Laboratory. Potential effects on wetland plants and on threatened and endangered species are discussed, along with a detailed description of the individual outfalls resulting from the effluent reduction program.

  18. LAMPF II workshop, Los Alamos National Laboratory, Los Alamos, New Mexico, February 1-4, 1982

    SciTech Connect

    Thiessen, H.A.

    1982-01-01

    This report contains the proceedings of the first LAMPF II Workshop held at Los Alamos February 1 to 4, 1982. Included are the talks that were available in written form. The conclusion of the participants was that there are many exciting areas of physics that will be addressed by such a machine.

  19. Los Alamos National Laboratory strategic directions

    SciTech Connect

    Hecker, S.

    1995-10-01

    It is my pleasure to welcome you to Los Alamos. I like the idea of bringing together all aspects of the research community-defense, basic science, and industrial. It is particularly important in today`s times of constrained budgets and in fields such as neutron research because I am convinced that the best science and the best applications will come from their interplay. If we do the science well, then we will do good applications. Keeping our eye focused on interesting applications will spawn new areas of science. This interplay is especially critical, and it is good to have these communities represented here today.

  20. Experience with confirmation measurement at Los Alamos

    SciTech Connect

    Marshall, R.S.; Wagner, R.P.; Hsue, F.

    1985-01-01

    Confirmation measurements are used at Los Alamos in support of incoming and outgoing shipment accountibility and for support of both at /sup 235/U and Pu inventories. Statistical data are presented to show the consistency of measurements on items of identical composition and on items measured at two facilitis using similar instruments. A description of confirmation measurement techniques used in support of /sup 235/U and Pu inventories and a discussion on the ability of the measurements to identify items with misstated SNM are given.

  1. Materials accounting at Los Alamos National Laboratory

    SciTech Connect

    Roberts, N.J.; Erkkila, B.H.; Kelso, H.F.

    1985-07-20

    The materials accounting system at Los Alamos has evolved from an ''80-column'' card system to a very sophisticated near-real-time computerized nuclear material accountability and safeguards system (MASS). The present hardware was designed and acquired in the late 70's and is scheduled for a major upgrade in fiscal year 1986. The history of the system from 1950 through the DYMAC of the late 70's up to the present will be discussed. The philosophy of the system along with the details of the system will be covered. This system has addressed the integrated problems of management, control, and accounting of nuclear material successfully. 8 refs., 3 figs., 1 tab.

  2. Environmental Programs at Los Alamos National Laboratory

    SciTech Connect

    Jones, Patricia

    2012-07-11

    Summary of this project is: (1) Teamwork, partnering to meet goals - (a) Building on cleanup successes, (b) Solving legacy waste problems, (c) Protecting the area's environment; (2) Strong performance over the past three years - (a) Credibility from four successful Recovery Act Projects, (b) Met all Consent Order milestones, (c) Successful ramp-up of TRU program; (3) Partnership between the National Nuclear Security Administration's Los Alamos Site Office, DOE Carlsbad Field Office, New Mexico Environment Department, and contractor staff enables unprecedented cleanup progress; (4) Continued focus on protecting water resources; and (5) All consent order commitments delivered on time or ahead of schedule.

  3. Los Alamos National Laboratory computer benchmarking 1982

    SciTech Connect

    Martin, J.L.

    1983-06-01

    Evaluating the performance of computing machinery is a continual effort of the Computer Research and Applications Group of the Los Alamos National Laboratory. This report summarizes the results of the group's benchmarking activities performed between October 1981 and September 1982, presenting compilation and execution times as well as megaflop rates for a set of benchmark codes. Tests were performed on the following computers: Cray Research, Inc. (CRI) Cray-1S; Control Data Corporation (CDC) 7600, 6600, Cyber 73, Cyber 825, Cyber 835, Cyber 855, and Cyber 205; Digital Equipment Corporation (DEC) VAX 11/780 and VAX 11/782; and Apollo Computer, Inc., Apollo.

  4. HIV Type 1 Molecular Epidemiology in pol and gp41 Genes Among Naive Patients from Mato Grosso do Sul State, Central Western Brazil

    PubMed Central

    da Silveira, Alexsander Augusto; Cardoso, Ludimila Paula Vaz; Francisco, Roberta Barbosa Lopes

    2012-01-01

    Abstract Antiretroviral naive patients (n=49) were recruited in central western Brazil (Campo Grande City/Mato Grosso do Sul State, located across the Bolivia and Paraguay borders). HIV-1 protease (PR), reverse transcriptase (RT), and env gp41 HR1 fragments were sequenced. Genetic diversity was analyzed by REGA/phylogenetic analyses. Intersubtype recombinants were identified by SimPlot/phylogenetic trees. PR/RT resistance was analyzed by Calibrated Population Resistance/Stanford databases. T-20 resistance in gp41 was assessed by Stanford, Los Alamos, and other sources. Of HIV-1 subtypes 65.3% were BPRBRT, 10.2% were CPRCRT, and 8.2% were F1PRF1RT. Intersubtype recombinants were 16.3%: four B/F1 and four B/C (two were “CRF31_BC-like”). The Pol-RT V75M mutation was detected in two homosexual partners; one patient had the T215S revertant mutation. T-20/gp41 resistance mutations were L44M (n=2) and V38A (n=1). The high percentage of non-B isolates (∼35%) highlights the importance of molecular surveillance studies in settings distant from the origin of the epidemic. Our data help elaborate the molecular epidemiological map of HIV-1 in Brazil. PMID:21790471

  5. HIV type 1 molecular epidemiology in pol and gp41 genes among naive patients from Mato Grosso do Sul State, central western Brazil.

    PubMed

    da Silveira, Alexsander Augusto; Cardoso, Ludimila Paula Vaz; Francisco, Roberta Barbosa Lopes; de Araújo Stefani, Mariane Martins

    2012-03-01

    Antiretroviral naive patients (n=49) were recruited in central western Brazil (Campo Grande City/Mato Grosso do Sul State, located across the Bolivia and Paraguay borders). HIV-1 protease (PR), reverse transcriptase (RT), and env gp41 HR1 fragments were sequenced. Genetic diversity was analyzed by REGA/phylogenetic analyses. Intersubtype recombinants were identified by SimPlot/phylogenetic trees. PR/RT resistance was analyzed by Calibrated Population Resistance/Stanford databases. T-20 resistance in gp41 was assessed by Stanford, Los Alamos, and other sources. Of HIV-1 subtypes 65.3% were B(PR)B(RT), 10.2% were C(PR)C(RT), and 8.2% were F1(PR)F1(RT). Intersubtype recombinants were 16.3%: four B/F1 and four B/C (two were "CRF31_BC-like"). The Pol-RT V75M mutation was detected in two homosexual partners; one patient had the T215S revertant mutation. T-20/gp41 resistance mutations were L44M (n=2) and V38A (n=1). The high percentage of non-B isolates (∼35%) highlights the importance of molecular surveillance studies in settings distant from the origin of the epidemic. Our data help elaborate the molecular epidemiological map of HIV-1 in Brazil.

  6. Specific sequences commonly found in the V3 domain of HIV-1 subtype C isolates affect the overall conformation of native Env and induce a neutralization-resistant phenotype independent of V1/V2 masking.

    PubMed

    Salomon, Aidy; Krachmarov, Chavdar; Lai, Zhong; Honnen, William; Zingman, Barry S; Sarlo, Julie; Gorny, Miroslaw K; Zolla-Pazner, Susan; Robinson, James E; Pinter, Abraham

    2014-01-01

    Primary HIV-1 isolates are relatively resistant to neutralization by antibodies commonly induced after infection or vaccination. This is generally attributed to masking of sensitive epitopes by the V1/V2 domain and/or glycans situated at various positions in Env. Here we identified a novel masking effect mediated by subtype C-specific V3 sequences that contributes to the V1/V2-independent and glycan-independent neutralization resistance of chimeric and primary Envs to antibodies directed against multiple neutralization domains. Positions at several conserved charged and hydrophobic sites in the V3 crown and stem were also shown to affect neutralization phenotype. These results indicated that substitutions typically present in subtype C and related V3 sequences influence the overall conformation of native Env in a way that occludes multiple neutralization targets located both within and outside of the V3 domain, and may reflect an alternative mechanism for neutralization resistance that is particularly active in subtype C and related isolates.

  7. HIV Transmission

    MedlinePlus

    ... pre-chewed by an HIV-infected person. The contamination occurs when infected blood from a caregiver’s mouth ... pre-chewed by an HIV-infected person. The contamination occurs when infected blood from a caregiver’s mouth ...

  8. Coreceptor usage of Chinese HIV-1 and impact of X4/DM transmission clusters among recently infected men who have sex with men.

    PubMed

    Li, Xiaoshan; Zhu, Kexin; Li, Wei; Fang, Kun; Musa, Taha Hussein; Song, Yue; Du, Guoping; Gao, Rong; Guo, Yan; Yan, Wenjuan; Xuan, Yang; Zhong, Ping; Wei, Pingmin

    2016-09-01

    To characterize the current frequency of HIV-1 coreceptor usage in China and assess the candidacy of CCR5 antagonists for treatment of HIV infections. In addition, we aimed to evaluate the potential of X4/DM virus transmission in recently infected men who have sex with men (MSM) individuals.Viral tropism testing was performed on samples from 399 MSM individuals and on 2408 available Chinese HIV-1 V3 sequences downloaded from the Los Alamos database using Geno2pheno and WebPSSM in combination. The transmission clusters were evaluated using pol sequences from 291 recently infected MSM with a maximum likelihood, maximum pairwise distance, and Bayesian inference.A higher prevalence of X4/DM viruses was observed in individuals infected with CRF01_AE strains than with subtype B (27.8% vs 12.2%, P < 0.001) and CRF07_BC/CRF08_BC/C (27.8% vs 1.0%, P < 0.001). Seven clusters containing only X4/DM viruses were detected in 40 transmission clusters. No significant difference in proportions between clustered X4/DM viruses and R5 viruses was found (P = 0.683).The high proportion of CXCR4 usage for CRF01_AE strains may result in the loss of susceptibility to maraviroc since CRF01_AE has become the most prevalent strains in China. The high prevalence of X4/DM viruses among recently CRF01_AE-infected individuals may be attributed to the stochasticity of HIV transmission, which implied that the early viral tropism screening and treatment would be the key for controlling the epidemic of CRF01_AE strains in China. PMID:27684870

  9. The Climate at Los Alamos; Are we measurement changes?

    SciTech Connect

    Dewart, Jean Marie

    2015-04-16

    A new report shows new graphic displays of the weather trends in Los Alamos, New Mexico, and at the Los Alamos National Laboratory (LANL). The graphs show trends of average, minimum average, and maximum average temperature for summer and winter months going back decades. Records of summer and winter precipitation are also included in the report.

  10. Human herpes virus-6 increases HIV-1 expression in co-infected T cells via nuclear factors binding to the HIV-1 enhancer.

    PubMed Central

    Ensoli, B; Lusso, P; Schachter, F; Josephs, S F; Rappaport, J; Negro, F; Gallo, R C; Wong-Staal, F

    1989-01-01

    Human Herpes virus-6 (HHV-6) can co-infect with HIV-1 human CD4+ T-cells, leading to accelerated cell death, and factors in HHV-6-infected cells stimulate HIV-1 LTR directed gene expression. In this study, we have examined the mechanism of HIV-1 activation by HHV-6 and localized the cis-acting sequences of HIV-1 LTR responsive to trans-activation. Increased HIV-1 LTR directed gene expression is obtained in HIV-1 infected cells co-infected with HHV-6, or in HHV-6 infected cells co-transfected with the HIV-1 tat gene. Parallel increases of HIV-1-specific transcripts are seen by in situ hybridization in HHV-6/HIV-1 doubly infected cells as compared to single HIV-1 infection. Similarly, infection by HHV-6 increases the steady-state level of HIV-1 LTR mRNA that parallels CAT enzymatic activity, suggesting a transcriptional and/or post-transcriptional activation. Sequences necessary for HIV-1 LTR activation by HHV-6 are distinct from those required for that tat response and map to a region of the HIV-1 LTR from -103 to -48. The HIV-1 enhancer sequence (-105 to -80) is sufficient to confer HHV-6 inducibility to a heterologous promoter, and nuclear protein(s) activated or induced by HHV-6 infection specifically bind to the NF kappa B motifs of the HIV-1 enhancer region.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:2573513

  11. Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naïve individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study.

    PubMed

    Nouhin, Janin; Donchai, Tawee; Hoang, Khanh Thu Huynh; Ken, Sreymom; Kamkorn, Jiraporn; Tran, Ton; Ayouba, Ahidjo; Peeters, Martine; Chaix, Marie-Laure; Lien, Truong Xuan; Nerrienet, Eric; Ngo-Giang-Huong, Nicole

    2011-01-01

    The HIV integrase enzyme is essential for the HIV life cycle as it mediates integration of HIV-1 proviral DNA into the infected cell's genome. Recently, the development of drugs capable of inhibiting integrase has provided major new options for HIV-infected, treatment-experienced patients with multidrug resistant virus, as well treatment-naïve patients. More than 40 amino acid substitutions within integrase have been described as associated mostly with resistance of HIV B-subtypes to currently available integrase inhibitors (INIs). We have analyzed the natural polymorphisms of the integrase coding region in 87 antiretroviral-naïve subjects (32 from Cambodia, 37 from Thailand and 18 from Vietnam) infected with CRF01_AE virus, the predominant HIV-1 strain circulating in Southeast Asia. The 864bp integrase coding region was sequenced using the ANRS consensus sequencing technique from plasma samples, and amino acid results were interpreted for drug resistance according to the ANRS (Updated July 2009, version 18) and Stanford algorithms (Version November 6, 2009). Alignment of the 87 amino acid sequences against the 2004 Los Alamos HIV-1 clade B consensus sequence showed that overall, 119 of 288 (41.3%) amino acid positions presented at least one polymorphism each. Substitutions found in >60% of study subjects occurred at: K14, A21, V31, S39, I72, T112, T124, T125, G134, I135, K136, D167, V201, L234 and S283. Also, new amino acid substitutions of as yet unknown significance were identified: E152K/H, S153F/L, N155I and E157G. None of the known integrase resistance mutations were observed, except E157Q found in one Cambodian subject (1.1%, CI 95% 0.02-6.3%). The clinical impact of this substitution on resistance of B and nonB-viruses to the licensed INI raltegravir is unclear. If this substitution is confirmed to compromise the virologic response to raltegravir, further studies will be needed to better assess the prevalence of this substitution among CRF01_AE virus.

  12. Frequency and implications of HIV superinfection.

    PubMed

    Redd, Andrew D; Quinn, Thomas C; Tobian, Aaron A R

    2013-07-01

    HIV superinfection occurs when an individual with HIV is infected with a new distinct HIV viral strain. Superinfection has been reported throughout the world, and studies have recorded incidence rates of 0-7·7% per year. Use of next-generation sequencing has improved detection of superinfection, which can be transmitted by injecting drug use and sexual intercourse. Superinfection might have incidence rates comparable to those of initial HIV infection. Clinicians should encourage safe sexual and injecting drug use practices for HIV-infected patients because superinfection has detrimental effects on clinical outcomes and could pose a concern for large-scale antiretroviral treatment plans. The occurrence of superinfection has implications for vaccine research, since it seems initial HIV infection is not fully protective against a subsequent infection. Additional collaborative research could benefit care of patients and inform future vaccine design.

  13. The Global Transmission Network of HIV-1

    PubMed Central

    Wertheim, Joel O.; Leigh Brown, Andrew J.; Hepler, N. Lance; Mehta, Sanjay R.; Richman, Douglas D.; Smith, Davey M.; Kosakovsky Pond, Sergei L.

    2014-01-01

    Human immunodeficiency virus type 1 (HIV-1) is pandemic, but its contemporary global transmission network has not been characterized. A better understanding of the properties and dynamics of this network is essential for surveillance, prevention, and eventual eradication of HIV. Here, we apply a simple and computationally efficient network-based approach to all publicly available HIV polymerase sequences in the global database, revealing a contemporary picture of the spread of HIV-1 within and between countries. This approach automatically recovered well-characterized transmission clusters and extended other clusters thought to be contained within a single country across international borders. In addition, previously undescribed transmission clusters were discovered. Together, these clusters represent all known modes of HIV transmission. The extent of international linkage revealed by our comprehensive approach demonstrates the need to consider the global diversity of HIV, even when describing local epidemics. Finally, the speed of this method allows for near-real-time surveillance of the pandemic's progression. PMID:24151309

  14. [Analysis of genetic recombination between human immunodeficiency virus type 1 (HIV-1) and HIV-2].

    PubMed

    Motomura, Kazushi

    2009-03-01

    It is estimated that one million people are dually infected with Human Immunodeficiency Virus type-I (HIV-1) and type-II (HIV-2) in West Africa and parts of India. HIV-1 and HIV-2 use the same receptor and coreceptors for entry into cells, and thus target the same cell populations in the host. Additionally, we first examined whether RNAs from HIV-1 and HIV-2 can be copackaged into the same virion. Therefore these properties suggest that in the dually infected population, it is likely that some cells can be infected by both HIV-1 and HIV-2, thereby providing opportunities for these two viruses to interact with each other. We constructed recombination assay system for measurement recombination frequencies and analyzed recombination rate between HIV-1 and HIV-2. We used modified near-full-length viruses that each contained a green fluorescent protein gene (gfp) with a different inactivating mutation. Thus, a functional gfp could be reconstituted via recombination, which was used to detect copackaging of HIV-1 and HIV-2 RNAs. In this study, approximately 0.2% of infection events generated the GFP phenotype. Therefore, the appearance of the GFP+ phenotype in the current system is approximately 35-fold lower than that between two homologous HIV-1 or HIV-2 viruses. We then mapped the general structures of the recombinant viruses and characterized the recombination junctions by DNA sequencing. We observed several different recombination patterns including those only had crossovers in gfp. The most common hybrid genomes had heterologous LTRs. Although infrequent, crossovers were also identified in the viral sequences. Such chimeric HIV-1 and HIV-2 viruses have yet to be observed in the infected population. It is unclear whether the lack of observed chimeras is due to the divergence between HIV-1 and HIV-2 being too great for such an event to occur, or whether such events could occur but have not yet been observed. Given the number of coinfected people, the potential for

  15. Carbon isotope chemostratigraphy and precise dating of middle Frasnian (lower Upper Devonian) Alamo Breccia, Nevada, USA

    USGS Publications Warehouse

    Morrow, J.R.; Sandberg, C.A.; Malkowski, K.; Joachimski, M.M.

    2009-01-01

    At Hancock Summit West, Nevada, western USA, uppermost Givetian (upper Middle Devonian) and lower and middle Frasnian (lower Upper Devonian) rocks of the lower Guilmette Formation include, in stratigraphic sequence, carbonate-platform facies of the conodont falsiovalis, transitans, and punctata Zones; the type Alamo Breccia Member of the middle punctata Zone; and slope facies of the punctata and hassi Zones. The catastrophically deposited Alamo Breccia and related phenomena record the ~ 382??Ma Alamo event, produced by a km-scale bolide impact into a marine setting seaward of an extensive carbonate platform fringing western North America. Re-evaluation of conodonts from the lower Guilmette Formation and Alamo Breccia Member, together with regional sedimentologic and conodont biofacies comparisons, now firmly locates the onset of the Johnson et al. (1985) transgressive-regressive (T-R) cycle IIc, which occurred after the start of the punctata Zone, within a parautochthonous megablock low in the Alamo Breccia. Whole-rock carbon isotope analyses through the lower Guilmette Formation and Alamo Breccia Member reveal two positive ??13Ccarb excursions: (1) a small, 3??? excursion, which is possibly correlative with the falsiovalis Event previously identified from sections in Western Europe and Australia, occurs below the breccia in the Upper falsiovalis Zone to early part of the transitans Zone; and (2) a large, multi-part excursion, dominated by a 6??? positive shift, begins above the start of the punctata Zone and onset of T-R cycle IIc and continues above the Alamo Breccia, ending near the punctata- hassi zonal boundary. This large excursion correlates with the punctata Event, a major positive ??13C excursion previously recognized in eastern Laurussia and northern Gondwana. Consistent with previous studies, at Hancock Summit West the punctata Event is apparently not associated with any regional extinctions or ecosystem reorganizations. In the study area, onset of the

  16. HIV Medication Adherence

    MedlinePlus

    HIV Treatment HIV Medication Adherence (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points Medication adherence means sticking ... exactly as prescribed. Why is adherence to an HIV regimen important? Adherence to an HIV regimen gives ...

  17. HIV among Transgender People

    MedlinePlus

    ... of transgender Virginians . Richmond, VA: Virginia HIV Community Planning Committee and Virginia Department of Health; 2007. Accessed April 14, 2016. Additional ... HIV/AIDS CDC HIV CDC HIV/AIDS ...

  18. [HIV lipodystrophy].

    PubMed

    Snopková, S; Matýsková, M; Povolná, K; Polák, P; Husa, P

    2010-12-01

    Combined antiretroviral therapy results in extraordinary decrease of morbidity and mortality of HIV-infected patients and in an essential change of the HIV/AIDS disease prognosis. However, long-term intake of antiretroviral medicaments is related to occurrence of metabolic and morphological abnormalities, of which some have been combined into a new syndrome--the so called HIV lipodystrophy. The HIV lipodystrophy syndrome covers metabolic and morphological changes. Metabolic changes include dyslipidaemia with hypercholesterolaemia and/or hypertriglyceridaemia, insulin resistance with hyperinsulinaemia and hyperlaktataemia. Morphological changes have the nature of lipoatrophia (loss of subcutaneous fat--on the cheeks, on extremities, on buttocks and marked prominence of surface veins) or lipohypertrophia (growth of fat tissue--on the chest, in the dorsocervical area, lipomatosis of visceral tissues and organs, fat accumulation in the abdominal area). Several HIV lipodystrophy features are very similar to the metabolic syndrome of the general population. That is why this new syndrome represents a prospective risk of premature atherosclerosis and increase of the cardiovascular risk in young HIV positive individuals. The article mentions major presented studies dealing with the relation of antiretroviral treatment and the cardiovascular risk. The conclusions of the studies are not unequivocal--this is, among others, given by the reason that their length is short from the viewpoint of atherogenesis. The major risk of subclinical atherosclerosis acceleration seems to be related to the deep immunodeficiency and low number of CD4+ lymphocytes and florid, uncontrolled HIV infection with a high number of HIV-1 RNA copies actually circulating in the plasma. The question, whether metabolic and morphological changes related to HIV and cART carry a similar atherogenic potential as in the general population, remains open for future. PMID:21261108

  19. Portable MRI developed at Los Alamos

    SciTech Connect

    Espy, Michelle

    2015-04-22

    Scientists at Los Alamos National Laboratory are developing an ultra-low-field Magnetic Resonance Imaging (MRI) system that could be low-power and lightweight enough for forward deployment on the battlefield and to field hospitals in the World's poorest regions. "MRI technology is a powerful medical diagnostic tool," said Michelle Espy, the Battlefield MRI (bMRI) project leader, "ideally suited for imaging soft-tissue injury, particularly to the brain." But hospital-based MRI devices are big and expensive, and require considerable infrastructure, such as large quantities of cryogens like liquid nitrogen and helium, and they typically use a large amount of energy. "Standard MRI machines just can't go everywhere," said Espy. "Soldiers wounded in battle usually have to be flown to a large hospital and people in emerging nations just don't have access to MRI at all. We've been in contact with doctors who routinely work in the Third World and report that MRI would be extremely valuable in treating pediatric encephalopathy, and other serious diseases in children." So the Los Alamos team started thinking about a way to make an MRI device that could be relatively easy to transport, set up, and use in an unconventional setting. Conventional MRI machines use very large magnetic fields that align the protons in water molecules to then create magnetic resonance signals, which are detected by the machine and turned into images. The large magnetic fields create exceptionally detailed images, but they are difficult and expensive to make. Espy and her team wanted to see if images of sufficient quality could be made with ultra-low-magnetic fields, similar in strength to the Earth's magnetic field. To achieve images at such low fields they use exquisitely sensitive detectors called Superconducting Quantum Interference Devices, or SQUIDs. SQUIDs are among the most sensitive magnetic field detectors available, so interference with the signal is the primary stumbling block. "SQUIDs are

  20. HIV among Women

    MedlinePlus

    ... testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS ... HIV infection—National HIV Behavioral Surveillance, 20 U.S. cities, 2013 . HIV Surveillance Special Report 13 . Accessed January ...

  1. Environmental surveillance at Los Alamos during 1987

    SciTech Connect

    Not Available

    1988-05-01

    This report describes the environmental surveillance program conducted by Los Alamos National Laboratory during 1987. Routine monitoring for radiation and radioactive or chemical materials is conducted on the Laboratory site as well as in the surrounding region. Monitoring results are used to determine compliance with appropriate standards and to permit early identification of potentially undesirable trends. Results and interpretation of data for 1987 cover: external penetrating radiation; quantities of airborne emissions and liquid effluents; concentrations of chemicals and radionuclides in ambient air, surface and ground waters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Comparisons with appropriate standards, regulations, and background levels provide the basis for concluding that environmental effects from Laboratory operations are insignificant and do not pose a threat to the public, Laboratory employees, or the environment. 113 refs., 33 figs., 120 tabs.

  2. Environmental surveillance at Los Alamos during 1995

    SciTech Connect

    1996-10-01

    This report describes the environmental surveillance program at Los Alamos National Laboratory (LANL or the Laboratory) during 1995. The Laboratory routinely monitors for radiation and for radioactive and nonradioactive materials at (or on) Laboratory sites as well as in the surrounding region. LANL uses the monitoring result to determine compliance with appropriate standards and to identify potentially undesirable trends. Data were collected in 1995 to assess external penetrating radiation; quantities of airborne emissions and liquid effluents; concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Using comparisons with standards, regulations, and background levels, this report concludes that environmental effects from Laboratory operations are small and do not pose a demonstrable threat to the public, Laboratory employees, or the environment.

  3. Environmental surveillance at Los Alamos during 1979

    SciTech Connect

    Not Available

    1980-04-01

    This report documents the environmental surveillance program conducted by the Los Alamos Scientific Laboratory (LASL) in 1979. Routine monitoring for radiation and radioactive or chemical substances was conducted on the Laboratory site and in the surrounding region to determine compliance with appropriate standards and permit early identification of possible undesirable trends. Results and interpretation of the data for 1979 on penetrating radiation, chemical and radiochemical quality of ambient air, surface and ground water, municipal water supply, soils and sediments, food, and airborne and liquid effluents are included. Comparisons with appropriate standards and regulations or with background levels from natural or other non-LASL sources provide a basis for concluding that environmental effects attributable to LASL operations are minor and cannot be considered likely to result in any hazard to the population of the area. Results of several special studies provide documentation of some unique environmental conditions in the LASL environs.

  4. Environmental surveillance at Los Alamos during 1989

    SciTech Connect

    Not Available

    1990-12-01

    This report describes the environmental surveillance program conducted by Los Alamos National Laboratory during 1989. Routine monitoring for radiation and radioactive or chemical materials is conducted on the Laboratory site as well as in the surrounding region. Monitoring results are used to determine compliance with appropriate standards and to permit early identification of potentially undesirable trends. Results and interpretation of data for 1989 cover external penetrating radiation; quantities of airborne emissions and effluents; concentrations of chemicals and radionuclides in ambient air, surface and ground waters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Comparisons with appropriate standards, regulations, and background levels provide the basis for concluding that environmental effects from Laboratory operations are small and do not pose a threat to the public, Laboratory employees, or the environment. 58 refs., 31 figs., 39 tabs.

  5. Environmental surveillance at Los Alamos during 1992

    SciTech Connect

    Kohen, K.; Stoker, A.; Stone, G.

    1994-07-01

    This report describes the environmental surveillance program at Los Alamos National Laboratory during 1992. The Laboratory routinely monitors for radiation and for radioactive and nonradioactive materials at (or on) Laboratory sites as well as in the surrounding region. LANL uses the monitoring results to determine compliance with appropriate standards and to identify potentially undesirable trends. Data were collected in 1992 to assess external penetrating radiation; quantities of airborne emissions and liquid effluents; concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Using comparisons with standards, regulations, and background levels, this report concludes that environmental effects from Laboratory operations are small and do not pose a demonstrable threat to the public, laboratory employees, or the environment.

  6. The Los Alamos Intense Neutron Source

    SciTech Connect

    Nebel, R.A.; Barnes, D.C.; Bollman, R.; Eden, G.; Morrison, L.; Pickrell, M.M.; Reass, W.

    1997-10-01

    The Intense Neutron Source (INS) is an Inertial Electrostatic Confinement (IEC) fusion device presently under construction at Los Alamos National Laboratory. It is designed to produce 10{sup 11} neutrons per second steady-state using D-T fuel. Phase 1 operation of this device will be as a standard three grid IEC ion focus device. Expected performance has been predicted by scaling from a previous IEC device. Phase 2 operation of this device will utilize a new operating scheme, the Periodically Oscillating Plasma Sphere (POPS). This scheme is related to both the Spherical Reflect Diode and the Oscillating Penning Trap. With this type of operation the authors hope to improve plasma neutron production to about 10{sup 13} neutrons/second.

  7. Information about Practicums at Los Alamos

    SciTech Connect

    Bradley, Paul A.

    2012-07-24

    The Los Alamos Neutron Science Center is the premier facility for neutron science experiments ranging from cross section measurements, neutron scattering experiments, proton radiography, cold neutrons, actinide neutronic properties, and many other exciting topics. The National High Magnetic Field Laboratory is home to several powerful magnets, including the one that created the first non-destructive 100 Tesla field in March 2012. They probe the electronic structure of superconductors, magnetic properties of materials (including magneto-quantum effects). Research is also conducted in correlated materials, thermoacoustics, and magnetic properties of actinides. The Trident Laser has a unique niche with very high power, short pulse experiments, with a peak power of 10{sup 20} W in short pulse mode. Discoveries range from production of monoenergetic MeV ion beam, nonlinear kinetic plasma waves, the transition between kinetic and fluid nonlinear behavior and other laser-plasma interaction processes.

  8. Environmental analysis of Lower Pueblo/Lower Los Alamos Canyon, Los Alamos, New Mexico

    SciTech Connect

    Ferenbaugh, R.W.; Buhl, T.E.; Stoker, A.K.; Becker, N.M.; Rodgers, J.C.; Hansen, W.R.

    1994-12-01

    The radiological survey of the former radioactive waste treatment plant site (TA-45), Acid Canyon, Pueblo Canyon, and Los Alamos Canyon found residual contamination at the site itself and in the channel and banks of Acid, Pueblo, and lower Los Alamos Canyons all the way to the Rio Grande. The largest reservoir of residual radioactivity is in lower Pueblo Canyon, which is on DOE property. However, residual radioactivity does not exceed proposed cleanup criteria in either lower Pueblo or lower Los Alamos Canyons. The three alternatives proposed are (1) to take no action, (2) to construct a sediment trap in lower Pueblo Canyon to prevent further transport of residual radioactivity onto San Ildefonso Indian Pueblo land, and (3) to clean the residual radioactivity from the canyon system. Alternative 2, to cleanup the canyon system, is rejected as a viable alternative. Thousands of truckloads of sediment would have to be removed and disposed of, and this effort is unwarranted by the low levels of contamination present. Residual radioactivity levels, under either present conditions or projected future conditions, will not result in significant radiation doses to persons exposed. Modeling efforts show that future transport activity will not result in any residual radioactivity concentrations higher than those already existing. Thus, although construction of a sediment trap in lower Pueblo Canyon is a viable alternative, this effort also is unwarranted, and the no-action alternative is the preferred alternative.

  9. Environmental surveillance at Los Alamos during 2009

    SciTech Connect

    Fuehne, David; Poff, Ben; Hjeresen, Denny; Isaacson, John; Johnson, Scot; Morgan, Terry; Paulson, David; Salzman, Sonja; Rogers, David

    2010-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (the Laboratory) environmental organization, as required by US Department of Energy Order 5400.1, General Environmental Protection Program, and US Department of Energy Order 231.1A, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory’s efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory’s major environmental programs and explains the risks and the actions taken to reduce risks at the Laboratory from environmental legacies and waste management operations. Chapter 2 reports the Laboratory’s compliance status for 2009. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations and discusses chemical exposures. The environmental surveillance and monitoring data are organized by environmental media (air in Chapter 4; water and sediments in Chapters 5 and 6; soils in Chapter 7; and foodstuffs and biota in Chapter 8) in a format to meet the needs of a general and scientific audience. Chapter 9 provides a summary of the status of environmental restoration work around LANL. The new Chapter 10 describes the Laboratory’s environmental stewardship efforts and provides an overview of the health of the Rio Grande. A glossary and a list of acronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the Laboratory’s technical

  10. Environmental surveillance at Los Alamos during 2008

    SciTech Connect

    Fuehne, David; Gallagher, Pat; Hjeresen, Denny; Isaacson, John; Johson, Scot; Morgan, Terry; Paulson, David; Rogers, David

    2009-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (the Laboratory) Environmental Programs Directorate, as required by US Department of Energy Order 450.1, General Environmental Protection Program, and US Department of Energy Order 231.1A, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory’s efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory’s major environmental programs and explains the risks and the actions taken to reduce risks at the Laboratory from environmental legacies and waste management operations. Chapter 2 reports the Laboratory’s compliance status for 2007. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations and discusses chemical exposures. The environmental surveillance and monitoring data are organized by environmental media (Chapter 4, air; Chapters 5 and 6, water and sediments; Chapter 7, soils; and Chapter 8, foodstuffs and biota) in a format to meet the needs of a general and scientific audience. Chapter 9 provides a summary of the status of environmental restoration work around LANL. A glossary and a list of acronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the Laboratory’s technical areas and their associated programs, and Appendix D provides web links to more information.

  11. Environmental surveillance at Los Alamos during 2005

    SciTech Connect

    2006-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (LANL or the Laboratory) environmental organization, as required by US Department of Energy Order 5400.1, General Environmental Protection Program, and US Department of Energy Order 231.IA, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory's efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory's major environmental programs. Chapter 2 reports the Laboratory's compliance status for 2005. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations. The environmental surveillance and monitoring data are organized by environmental media (Chapter 4, Air; Chapters 5 and 6, Water and Sediments; Chapter 7, Soils; and Chapter 8, Foodstuffs and Biota) in a format to meet the needs of a general and scientific audience. Chapter 9, new for this year, provides a summary of the status of environmental restoration work around LANL. A glossary and a list ofacronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the Laboratory's technical areas and their associated programs, and Appendix D provides web links to more information.

  12. HIV / AIDS

    MedlinePlus

    ... Marketing Share this: Main Content Area Understanding HIV/AIDS AIDS was first reported in the United States in ... and has since become a major worldwide epidemic. AIDS is caused by the human immunodeficiency virus, or ...

  13. HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission.

    PubMed

    Collins-Fairclough, Aneisha M; Dennis, Ann M; Nelson, Julie A E; Weir, Sharon S; Figueroa, J Peter

    2015-08-01

    The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict drug resistance mutations. An HIV drug resistance prevalence of 28% (minimum 13%) was observed among this cohort, with the most frequent mutations conferring resistance to efavirenz, nevirapine, and lamivudine. Phylogenetic analysis of the sequences revealed 10 times the number of linked HIV infections among this cohort than respondent reporting. HIV treatment and prevention efforts in Jamaica could benefit significantly from Pol genotyping of the HIV strains infecting socially vulnerable MSM prior to initiating antiretroviral therapy (ART), as this would guide suppressive ART and unearth HIV transmission clusters to enable more effective delivery of treatment and prevention programs. PMID:26133540

  14. HIV Drug Resistance Surveillance Among Jamaican Men Who Have Sex with Men Should Be Prioritized for Reducing HIV Transmission

    PubMed Central

    Dennis, Ann M.; Nelson, Julie A.E.; Weir, Sharon S.; Figueroa, J. Peter

    2015-01-01

    Abstract The prevalence of human immunodeficiency virus type 1 (HIV-1) is highest among men who have sex with men (MSM) in Jamaica but no genotypic data are available on the virus strains that are responsible for the epidemic among this key population. HIV-1 polymerase (pol) genes from 65 MSM were sequenced and used to predict drug resistance mutations. An HIV drug resistance prevalence of 28% (minimum 13%) was observed among this cohort, with the most frequent mutations conferring resistance to efavirenz, nevirapine, and lamivudine. Phylogenetic analysis of the sequences revealed 10 times the number of linked HIV infections among this cohort than respondent reporting. HIV treatment and prevention efforts in Jamaica could benefit significantly from Pol genotyping of the HIV strains infecting socially vulnerable MSM prior to initiating antiretroviral therapy (ART), as this would guide suppressive ART and unearth HIV transmission clusters to enable more effective delivery of treatment and prevention programs. PMID:26133540

  15. Production of the p24 capsid protein from HIV-1 subtype C in Arabidopsis thaliana and Daucus carota using an endoplasmic reticulum-directing SEKDEL sequence in protein expression constructs.

    PubMed

    Lindh, Ingrid; Wallin, Anita; Kalbina, Irina; Sävenstrand, Helena; Engström, Peter; Andersson, Sören; Strid, Ake

    2009-07-01

    An optimized gene expression construct was designed in order to increase the accumulation of the HIV-1 subtype C p24 protein in Arabidopsis thaliana and carrot (Daucus carota) plants. An ER retention signal was introduced into the genetic construct generating a p24 protein containing a SEKDEL amino acid sequence at its C-terminus. Mature A. thaliana plants and carrot cells were transformed using Agrobacterium tumefaciens carrying the improved pGreen0229/p24_SEKDEL vector. Several transgenic plant lines were obtained from both plant species by growth on selective medium and confirmed by PCR. Transformed lines were analyzed for p24 protein content by western blotting using anti-p24-specific antibodies and by Southern blotting to establish the number of copies of the insert in the plant nuclear genome. To estimate the accumulation levels of p24 protein in the plants, ELISA was run using soluble plant extracts. By comparing these results with our previous findings, the ER retention signal increased the level of p24 protein fivefold in the A. thaliana plants. In carrot taproot, the content of p24_SEKDEL protein was approximately half of that in Arabidopsis on a fresh weight basis and was stable in planta for several months. However, on a total soluble protein basis, carrots produced considerable higher levels of the p24_SEKDEL protein than Arabidopsis.

  16. High Proportion of HIV Serodiscordance among HIV-Affected Married Couples in Northern Vietnam

    PubMed Central

    Sawada, Ikumi; Tanuma, Junko; Do, Cuong Duy; Doan, Tra Thu; Luu, Quynh Phuong; Nguyen, Lan Anh Thi; Vu, Tuong Van Thi; Nguyen, Tuan Quang; Tsuchiya, Naho; Shiino, Teiichiro; Yoshida, Lay-Myint; Pham, Thanh Thuy Thi; Ariyoshi, Koya; Oka, Shinichi

    2015-01-01

    Introduction Little is known about the state of HIV transmission among married couples in Vietnam. This study aims to clarify HIV serostatus in this group and elucidate risk factors for intra-marital HIV transmission. Methods In 2012, we enrolled a group of HIV-positive married men registered at the HIV outpatient clinic of a referral hospital in northern Vietnam, along with their wives. Sociodemographic, behavioural and clinical data were collected from men and wives. HIV serodiscordant couples were followed until March 2014 to determine seroconversion rate. A phylogenetic analysis was performed based on env V3 sequence to detail cluster formation among men. Results Of the 163 HIV-positive men enrolled in the study, 101 (62.0%) had wives testing HIV-negative. Half of men reported injecting drug use (IDU) as a likely transmission route. Couples reported a high incidence of unprotected sexual intercourse prior to diagnosis; the median (inter quartile range) was 4 (4–8) times per month. Only 17 couples (10.4%) reported using condoms during at least half these instances. Multivariable analysis revealed IDU history among men was independently associated with HIV-negative wives (adjusted OR 0.31; 95% CI 0.10–0.95, p=0.041). Phylogenetic analysis of 80 samples indicated CRF01_AE. Of these, 69 (86.3%) clustered with IDU-associated viruses from Vietnam. No HIV seroconversion was identified during a follow-up of 61 serodiscordant couples, with 126.5 person-years of observation during which HIV-infected men were on antiretroviral drug therapy (ART). Conclusion High HIV serodiscordance was observed among HIV-affected married couples in northern Vietnam. A large number of at-risk wives therefore remain HIV-negative and can be protected with measures including proper use of ART if couples are made aware of the serodiscordance through screening. PMID:25898138

  17. HIV-1 RNA quantification in CRF02_AG HIV-1 infection: too easy to make mistakes.

    PubMed

    Tatarelli, Paola; Taramasso, Lucia; Di Biagio, Antonio; Sticchi, Laura; Nigro, Nicola; Barresi, Renata; Viscoli, Claudio; Bruzzone, Bianca

    2016-04-01

    The number of patients newly infected by HIV-1 non-B subtypes and circulating recombinant forms (CRFs) is increasing worldwide, including in the western countries. We report on a primary HIV-1 infection in a Caucasian patient. A routine quantitative assay (Nuclisens EasyQ HIV-1 2.0, BioMérieux SA) showed 6,700 HIV-1 RNA copies/ml. A combined antiretroviral therapy (cART) consistent with low baseline HIV-1 RNA was started. Few days later, the analysis performed with REGA HIV-1 Subtyping Tool - Version 3.0 attributed the HIV-1 sequence to the CRF02_AG recombinant form. Therefore, a second real-time PCR assay was performed, using the Versant HIV-1 RNA 1.0 Assay (kPCR) (Siemens HealthCare Diagnostics) which revealed a HIV-1 RNA of 230,000 copies/ml. Consequently, the ongoing cART was potentiated. This case suggests that the wide genetic variability of HIV-1 subtypes may affect the capability of the commonly used assays to detect and accurately quantify HIV-1 RNA in non-B subtypes and CRFs. In presence of CRFs different commercial HIV-1 RNA tests should be performed to find the most reliable for viral load quantification at the diagnosis, because it influences the choice of cART, and during the follow-up. Indeed, international guidelines for HIV-1 infection management suggest to monitor patient' HIV-RNA with the same assay over the course of treatment. As different commercial tests can be performed in the same laboratory with considerable difficulty, the laboratory should select an assay that is suitable not only for the more prevalent strain, but also for less frequent ones that, nevertheless, can occur. Then, knowing and investigating the spread of non-B strains has essential clinical and laboratory implications. PMID:27196556

  18. Signature Peptide-Enabled Metagenomics (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    SciTech Connect

    McMahon, Ben

    2012-06-01

    Ben McMahon of Los Alamos National Laboratory (LANL) presents "Signature Peptide-Enabled Metagenomics" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  19. Signature Peptide-Enabled Metagenomics (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    ScienceCinema

    McMahon, Ben [LANL

    2016-07-12

    Ben McMahon of Los Alamos National Laboratory (LANL) presents "Signature Peptide-Enabled Metagenomics" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  20. Explosive Flux Compression: 50 Years of Los Alamos Activities

    SciTech Connect

    Fowler, C.M.; Thomson, D.B.; Garn, W.B.

    1998-10-18

    Los Alamos flux compression activities are surveyed, mainly through references in view of space limitations. However, two plasma physics programs done with Sandia National Laboratory are discussed in more detail.

  1. Review of liquid metal heat pipe work at Los Alamos

    NASA Astrophysics Data System (ADS)

    Reid, Robert S.; Merrigan, Michael A.; Sena, J. Tom

    A survey of space-power related liquid metal heat pipe work at Los Alamos National Laboratory is presented. Heat pipe development at Los Alamos has been on-going since 1963. Heat pipes were initially developed for thermionic nuclear-electrical power production in space. Since then Los Alamos has developed liquid metal heat pipes for numerous applications related to high temperature systems in both the space and terrestrial environments. Some of these applications include thermionic electrical generators, thermoelectric energy conversion (both in-core and direct radiation), thermal energy storage, hypersonic vehicle leading edge cooling, and heat pipe vapor laser cells. Some of the work performed at Los Alamos has been documented in internal reports that are often little-known. A representative description and summary of progress in space-related liquid metal heat pipe technology is provided followed by a reference section citing sources where these works may be found.

  2. Review of liquid metal heat pipe work at Los Alamos

    SciTech Connect

    Reid, R.S.; Merrigan, M.A.; Sena, J.T. )

    1991-01-10

    A survey of space-power related liquid metal heat pipe work at Los Alamos National Laboratory is presented. Heat pipe development at Los Alamos has been on-going since 1963. Heat pipes were initially developed for thermionic nuclear-electrical power production in space. Since then Los Alamos has developed liquid metal heat pipes for numerous applications related to high temperature systems in both the space and terrestrial environments. Some of these applications include thermionic electrical generators, thermoelectric energy conversion (both in-core and direct radiation), thermal energy storage, hypersonic vehicle leading edge cooling, and heat pipe vapor laser cells. Some of the work performed at Los Alamos has been documented in internal reports that are often little-known. A representative description and summary of progress in space-related liquid metal heat pipe technology is provided followed by a reference section citing sources where these works may be found.

  3. Review of liquid metal heat pipe work at Los Alamos

    NASA Astrophysics Data System (ADS)

    Reid, Robert S.; Merrigan, Michael A.; Sena, J. Tom

    1991-01-01

    A survey of space-power related liquid metal heat pipe work at Los Alamos National Laboratory is presented. Heat pipe development at Los Alamos has been on-going since 1963. Heat pipes were initially developed for thermionic nuclear-electrical power production in space. Since then Los Alamos has developed liquid metal heat pipes for numerous applications related to high temperature systems in both the space and terrestrial environments. Some of these applications include thermionic electrical generators, thermoelectric energy conversion (both in-core and direct radiation), thermal energy storage, hypersonic vehicle leading edge cooling, and heat pipe vapor laser cells. Some of the work performed at Los Alamos has been documented in internal reports that are often little-known. A representative description and summary of progress in space-related liquid metal heat pipe technology is provided followed by a reference section citing sources where these works may be found.

  4. Review of liquid metal heat pipe work at Los Alamos

    NASA Astrophysics Data System (ADS)

    Reid, Robert S.; Merrigan, Michael A.; Sena, J. T.

    A survey of space-power related liquid metal heat pipe work at Los Alamos National Laboratory is presented. Heat pipe development at Los Alamos has been on-going since 1963. Heat pipes were initially developed for thermionic nuclear-electrical power production in space. Since then Los Alamos has developed liquid metal heat pipes for numerous applications related to high temperature systems in both the space and terrestrial environments. Some of these applications include thermionic electrical generators, thermoelectric energy conversion (both in-core and direct radiation), thermal energy storage, hypersonic vehicle leading edge cooling, and heat pipe vapor laser cells. Some of the work performed at Los Alamos has been documented in internal reports that are often little-known. A representative description and summary of progress in space-related liquid metal heat pipe technology is provided followed by reference section citing sources where these works may be found.

  5. Review of liquid metal heat pipe work at Los Alamos

    SciTech Connect

    Reid, R.S.; Merrigan, M.A.; Sena, J.T.

    1990-01-01

    A survey of space-power related liquid metal heat pipe work at Los Alamos National Laboratory is presented. Heat pipe development at Los Alamos has been on-going since 1963. Heat pipes were initially developed for thermionic nuclear-electrical power production in space. Since then Los Alamos has developed liquid metal heat pipes for numerous applications related to high temperature systems in both the space and terrestrial environments. Some of these applications include thermionic electrical generators, thermoelectric energy conversion (both in-core and direct radiation), thermal energy storage, hypersonic vehicle leading edge cooling, and heat pipe vapor laser cells. Some of the work performed at Los Alamos has been documented in internal reports that are often little-known. A representative description and summary of progress in space-related liquid metal heat pipe technology is provided followed by a reference section citing sources where these works may be found. 53 refs.

  6. Environmental Surveillance at Los Alamos during 2007

    SciTech Connect

    2008-09-30

    Environmental Surveillance at Los Alamos reports are prepared annually by the Los Alamos National Laboratory (the Laboratory) Environmental Directorate, as required by US Department of Energy Order 450.1, General Environmental Protection Program, and US Department of Energy Order 231.1A, Environment, Safety, and Health Reporting. These annual reports summarize environmental data that are used to determine compliance with applicable federal, state, and local environmental laws and regulations, executive orders, and departmental policies. Additional data, beyond the minimum required, are also gathered and reported as part of the Laboratory’s efforts to ensure public safety and to monitor environmental quality at and near the Laboratory. Chapter 1 provides an overview of the Laboratory’s major environmental programs and explains the risks and the actions taken to reduce risks at the Laboratory from environmental legacies and waste management operations. Chapter 2 reports the Laboratory’s compliance status for 2007. Chapter 3 provides a summary of the maximum radiological dose the public and biota populations could have potentially received from Laboratory operations and discusses chemical exposures. The environmental surveillance and monitoring data are organized by environmental media (Chapter 4, air; Chapters 5 and 6, water and sediments; Chapter 7, soils; and Chapter 8, foodstuffs and biota) in a format to meet the needs of a general and scientific audience. Chapter 9 provides a summary of the status of environmental restoration work around LANL. A glossary and a list of acronyms and abbreviations are in the back of the report. Appendix A explains the standards for environmental contaminants, Appendix B explains the units of measurements used in this report, Appendix C describes the laboratory’s technical areas and their associated programs, and Appendix D provides web links to more information. In printed copies of this report or Executive Summary, we have

  7. Envelope gene evolution and HIV-1 neuropathogenesis

    PubMed Central

    Vázquez-Santiago, Fabián J.; Rivera-Amill, Vanessa

    2016-01-01

    In the era of combined antiretroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) account for 40 to 56% of all HIV+ cases. During the acute stage of HIV-1 infection (<6 months), the virus invades and replicates within the central nervous system (CNS). Compared to peripheral tissues, the local CNS cell population expresses distinct levels of chemokine receptors, which levels exert selective pressure on the invading virus. HIV-1 envelope (env) sequences recovered from the brains and cerebrospinal fluid (CSF) of neurocognitively impaired HIV+ subjects often display higher nucleotide variability as compared to non-impaired HIV+ subjects. Specifically, env evolution provides HIV-1 with the strategies to evade host immune response, to reduce chemokine receptor dependence, to increase co-receptor binding efficiency, and to potentiate neurotoxicity. The evolution of env within the CNS leads to changes that may result in the emergence of novel isolates with neurotoxic and neurovirulent features. However, whether specific factors of HIV-1 evolution lead to the emergence of neurovirulent and neurotropic isolates remains ill-defined. HIV-1 env evolution is an ongoing phenomenon that occurs independently of neurological and neurocognitive disease severity; thus HIV env evolution may play a pivotal and reciprocal role in the etiology of HAND. Despite the use of cART, the reactivation of latent viral reservoirs represents a clinical challenge because of the replenishment of the viral pool that may subsequently lead to persistent infection. Therefore, gaining a more complete understanding of how HIV-1 env evolves over the course of the disease should be considered for the development of future therapies aimed at controlling CNS burden, diminishing persistent viremia, and eradicating viral reservoirs. Here we review the current literature on the role of HIV-1 env evolution in the setting of HAND disease progression and on the impact of cART on the dynamics of

  8. Mutagenicity and pausing of HIV reverse transcriptase during HIV plus-strand DNA synthesis.

    PubMed Central

    Ji, J; Hoffmann, J S; Loeb, L

    1994-01-01

    The unusually high frequency of misincorporation by HIV-1 reverse transcriptase (HIV RT) is likely to be the major factor in the rapid accumulation of viral mutations in AIDS, especially in the env gene. To investigate the ability of HIV RT to copy the env gene, we subcloned an HIV env gene fragment into a single-stranded DNA vector and measured the progression of synthesis by HIV RT. We observed that HIV RT, but not RT from avian myeloblastosis virus, DNA polymerase-alpha or T7 DNA polymerase, pauses specifically at poly-deoxyadenosine stretches within the env gene. The frequency of bypassing the polyadenosine stretches by HIV RT is enhanced by increasing the ratio of enzyme to template. We measured the fidelity of DNA synthesis within a segment of the hypervariable region 1 of the env gene (V-1) containing a poly-deoxyadenosine sequence by repetitively copying the DNA by HIV RT, and then cloning and sequencing the copied fragments. We found that 27% of the errors identified in V-1 sequence were frameshift mutations opposite the poly-adenosine tract, a site where strong pausing was observed. Pausing of HIV RT at the polyadenosine tract could be enhanced by either distamycin A or netropsin, (A-T)-rich minor groove binding peptides. Moreover, netropsin increases the frequency of frameshift mutations in experiments in which HIV RT catalyzes gap filling synthesis within the lacZ gene in double-stranded circular M13mp2 DNA. These combined results suggest that the enhanced mutation frequency may be due to increased pausing at netropsin-modified polyadenosine tracts. Therefore, netropsin and related A-T binding chemicals may selectively enhance frameshift mutagenesis induced by HIV RT and yield predominantly non-viable virus. Images PMID:7510388

  9. Strategic defense initiatives at Los Alamos National Laboratory

    SciTech Connect

    Rockwood, S.D.

    1985-01-01

    This presentation reviews the Strategic Defense Initiative (SDI) programs at Los Alamos National Laboratory, noting especially the needs for and applications of optics and optical technologies. Table I lists the various activities at Los Alamos contributing to SDI programs. The principal, nonnuclear SDI programs are: (1) the free-electron laser, and (2) neutral particle beams. Both should be considered as potential long-range-kill systems, but still in the futuristic category.

  10. HIV Latency

    PubMed Central

    Siliciano, Robert F.; Greene, Warner C.

    2011-01-01

    HIV-1 can establish a state of latent infection at the level of individual T cells. Latently infected cells are rare in vivo and appear to arise when activated CD4+ T cells, the major targets cells for HIV-1, become infected and survive long enough to revert back to a resting memory state, which is nonpermissive for viral gene expression. Because latent virus resides in memory T cells, it persists indefinitely even in patients on potent antiretroviral therapy. This latent reservoir is recognized as a major barrier to curing HIV-1 infection. The molecular mechanisms of latency are complex and include the absence in resting CD4+ T cells of nuclear forms of key host transcription factors (e.g., NFκB and NFAT), the absence of Tat and associated host factors that promote efficient transcriptional elongation, epigenetic changes inhibiting HIV-1 gene expression, and transcriptional interference. The presence of a latent reservoir for HIV-1 helps explain the presence of very low levels of viremia in patients on antiretroviral therapy. These viruses are released from latently infected cells that have become activated and perhaps from other stable reservoirs but are blocked from additional rounds of replication by the drugs. Several approaches are under exploration for reactivating latent virus with the hope that this will allow elimination of the latent reservoir. PMID:22229121

  11. Los Alamos low-level waste performance assessment status

    SciTech Connect

    Wenzel, W.J.; Purtymun, W.D.; Dewart, J.M.; Rodgers, J.E.

    1986-06-01

    This report reviews the documented Los Alamos studies done to assess the containment of buried hazardous wastes. Five sections logically present the environmental studies, operational source terms, transport pathways, environmental dosimetry, and computer model development and use. This review gives a general picture of the Los Alamos solid waste disposal and liquid effluent sites and is intended for technical readers with waste management and environmental science backgrounds but without a detailed familiarization with Los Alamos. The review begins with a wide perspective on environmental studies at Los Alamos. Hydrology, geology, and meteorology are described for the site and region. The ongoing Laboratory-wide environmental surveillance and waste management environmental studies are presented. The next section describes the waste disposal sites and summarizes the current source terms for these sites. Hazardous chemical wastes and liquid effluents are also addressed by describing the sites and canyons that are impacted. The review then focuses on the transport pathways addressed mainly in reports by Healy and Formerly Utilized Sites Remedial Action Program. Once the source terms and potential transport pathways are described, the dose assessment methods are addressed. Three major studies, the waste alternatives, Hansen and Rogers, and the Pantex Environmental Impact Statement, contributed to the current Los Alamos dose assessment methodology. Finally, the current Los Alamos groundwater, surface water, and environmental assessment models for these mesa top and canyon sites are described.

  12. The Los Alamos high-brightness photoinjector

    SciTech Connect

    O'Shea, P.G.

    1991-01-01

    For a number of years Los Alamos National Laboratory has been developing photocathode RF guns for high-brightness electron beam applications such as free-electron lasers (FELs). Previously thermionic high-voltage guns have been the source of choice for the electron accelerators used to drive FELs. The performance of such FELs is severely limited by the emittance growth produced by the subharmonic bunching process and also by the low peak current of the source. In a photoinjector, a laser driven photocathode is placed directly in a high-gradient RF accelerating cavity. A photocathode allows unsurpassed control over the current, and the spatial and temporal profile of the beam. In addition the electrodeless emission'' avoids many of the difficulties associated with multi-electrode guns, i.e. the electrons are accelerated very rapidly to relativistic energies, and there are no electrodes to distort the accelerating fields. For the past two years we have been integrating a photocathode into our existing FEL facility by replacing our thermionic gun and subharmonic bunchers with a high-gradient 1.3 GHz photoinjector. The photoinjector, which is approximately 0.6 m in length, produces 6 MeV, 300 A, 15 ps linac, and accelerated to a final energy of 40 MeV. We have recently begun lasing at wavelengths near 3 {mu}m. 16 refs., 2 figs., 5 tabs.

  13. NIST--Los Alamos racetrack microtron status

    SciTech Connect

    Wilson, M.A.; Ayres, R.L.; Cutler, R.I.; Debenham, P.H.; Lindstrom, E.R.; Mohr, D.L.; Penner, S.; Rose, J.E.; Young, L.M.

    1988-01-01

    The NIST-Los Alamos Racetrack Microtron (RTM) is designed to deliver a low-emittance electron beam of up to 0.5 mA cw over an energy range of 17 MeV to 185 MeV. Fed by a 5 MeV injector, the RTM contains two 180/degree/ end magnets that recirculate the beam up to 15 times through a 12 MeV RF linac. The linac, which operates in a standing-wave mode at 2380 MHz, has been tested to nearly full RF power. At present, the injector has undergone beam tests, and the beam transport system is complete through the 12 MeV linac. A temporary beam line has been installed at the exit of one end magnet to measure the beam energy, energy spread, and emittance after one pass through the accelerator. Preliminary results indicate that the accelerated beam energy spread and emittance are within design goals. 4 refs., 7 figs.

  14. Historic Manhattan Project Sites at Los Alamos

    SciTech Connect

    McGehee, Ellen

    2014-05-22

    The Manhattan Project laboratory constructed at Los Alamos, New Mexico, beginning in 1943, was intended from the start to be temporary and to go up with amazing speed. Because most of those WWII-era facilities were built with minimal materials and so quickly, much of the original infrastructure was torn down in the late '40s and early '50s and replaced by more permanent facilities. However, a few key facilities remained, and are being preserved and maintained for historic significance. Four such sites are visited briefly in this video, taking viewers to V-Site, the buildings where the first nuclear explosive device was pre-assembled in preparation for the Trinity Test in Southern New Mexico. Included is another WWII area, Gun Site. So named because it was the area where scientists and engineers tested the so-called "gun method" of assembling nuclear materials -- the fundamental design of the Little Boy weapon that was eventually dropped on Hiroshima. The video also goes to Pajarito Site, home of the "Slotin Building" and "Pond Cabin." The Slotin Building is the place where scientist Louis Slotin conducted a criticality experiment that went awry in early 1946, leading to his unfortunate death, and the Pond Cabin served the team of eminent scientist Emilio Segre who did early chemistry work on plutonium that ultimately led to the Fat Man weapon.

  15. Expanded recycling at Los Alamos National Laboratory

    SciTech Connect

    Betschart, J.F.; Malinauskas, L.; Burns, M.

    1996-07-01

    The Pollution Prevention Program Office has increased recycling activities, reuse, and options to reduce the solid waste streams through streamlining efforts that applied best management practices. The program has prioritized efforts based on volume and economic considerations and has greatly increased Los Alamos National Laboratory`s (LANL`s) recycle volumes. The Pollution Prevention Program established and chairs a Solid Waste Management Solutions Group to specifically address and solve problems in nonradioactive, Resource Conservation and Recovery Act (RCRA), state-regulated, and sanitary and industrial waste streams (henceforth referred to as sanitary waste in this paper). By identifying materials with recycling potential, identifying best management practices and pathways to return materials for reuse, and introducing the concept and practice of {open_quotes}asset management,{open_quotes} the Group will divert much of the current waste stream from disposal. This Group is developing procedures, agreements, and contracts to stage, collect, sort, segregate, transport and process materials, and is also garnering support for the program through the involvement of upper management, facility managers, and generators.

  16. Historic Manhattan Project Sites at Los Alamos

    ScienceCinema

    McGehee, Ellen

    2016-07-12

    The Manhattan Project laboratory constructed at Los Alamos, New Mexico, beginning in 1943, was intended from the start to be temporary and to go up with amazing speed. Because most of those WWII-era facilities were built with minimal materials and so quickly, much of the original infrastructure was torn down in the late '40s and early '50s and replaced by more permanent facilities. However, a few key facilities remained, and are being preserved and maintained for historic significance. Four such sites are visited briefly in this video, taking viewers to V-Site, the buildings where the first nuclear explosive device was pre-assembled in preparation for the Trinity Test in Southern New Mexico. Included is another WWII area, Gun Site. So named because it was the area where scientists and engineers tested the so-called "gun method" of assembling nuclear materials -- the fundamental design of the Little Boy weapon that was eventually dropped on Hiroshima. The video also goes to Pajarito Site, home of the "Slotin Building" and "Pond Cabin." The Slotin Building is the place where scientist Louis Slotin conducted a criticality experiment that went awry in early 1946, leading to his unfortunate death, and the Pond Cabin served the team of eminent scientist Emilio Segre who did early chemistry work on plutonium that ultimately led to the Fat Man weapon.

  17. Saving Water at Los Alamos National Laboratory

    SciTech Connect

    Erickson, Andy

    2015-03-16

    Los Alamos National Laboratory decreased its water usage by 26 percent in 2014, with about one-third of the reduction attributable to using reclaimed water to cool a supercomputing center. The Laboratory's goal during 2014 was to use only re-purposed water to support the mission at the Strategic Computing Complex. Using reclaimed water from the Sanitary Effluent Reclamation Facility, or SERF, substantially decreased water usage and supported the overall mission. SERF collects industrial wastewater and treats it for reuse. The reclamation facility contributed more than 27 million gallons of re-purposed water to the Laboratory's computing center, a secured supercomputing facility that supports the Laboratory’s national security mission and is one of the institution’s larger water users. In addition to the strategic water reuse program at SERF, the Laboratory reduced water use in 2014 by focusing conservation efforts on areas that use the most water, upgrading to water-conserving fixtures, and repairing leaks identified in a biennial survey.

  18. Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART.

    PubMed

    Vazquez-Guillen, Jose Manuel; Palacios-Saucedo, Gerardo C; Rivera-Morales, Lydia G; Garcia-Campos, Jorge; Ortiz-Lopez, Rocio; Noguera-Julian, Marc; Paredes, Roger; Vielma-Ramirez, Herlinda J; Ramirez, Teresa J; Chavez-Garcia, Marcelino; Lopez-Guillen, Paulo; Briones-Lara, Evangelina; Sanchez-Sanchez, Luz M; Vazquez-Martinez, Carlos A; Rodriguez-Padilla, Cristina

    2016-01-01

    Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM's) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM's in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM's during STI. PMID:26807922

  19. Doubly catalytic sensing of HIV-1-related CCR5 sequence in prokaryotic cell-free translation system using riboregulator-controlled luciferase activity.

    PubMed

    Sando, Shinsuke; Narita, Atsushi; Abe, Kenji; Aoyama, Yasuhiro

    2005-04-20

    A molecular-beacon-type riboregulator (mRNA) was applied to multiply catalytic gene sensing. It consists of a reporter gene for firefly protein luciferase and, upstream thereof, a regulator hairpin domain composed of an RBS/anti-RBS stem (RBS = ribosome binding site) and a loop which is complementary to the target. The hairpin and, hence, the RBS are rendered open upon binding of a target oligonucleotide of the human CC chemokine receptor 5 sequence in a prokaryotic cell-free translation system (10 muL) to ignite ribosomal catalytic translation, or transcription/translation when using a DNA form of the probe, to produce luciferase, which is assayed by a catalytic chemiluminescence reaction. The sensing, using an unmodified RNA or even dsDNA as a probe with a chemiluminescence output, is thus doubly catalytic or amplifiable with a sensitivity at

  20. HIV Life Cycle

    MedlinePlus

    HIV Overview The HIV Life Cycle (Last updated 9/8/2016; last reviewed 9/8/2016) Key Points HIV gradually destroys the immune ... life cycle. What is the connection between the HIV life cycle and HIV medicines? Antiretroviral therapy (ART) ...

  1. Camp HIV.

    PubMed

    Grodeck, B

    1995-01-01

    Innovative retreats for HIV-positive travelers specialize in stress reduction and alternative healing. The author gives a first-hand account of experiencing a wellness vacation for the HIV-positive. Although wellness retreats are nothing new, a San Francisco-based travel company picked the island of Hawaii as the specialized testing ground. The retreats guarantee a safe environment with a dose of restoration. Individuals spend seven days at the retreat center, Kalani Honua. Stress management workshops focus on yoga, principles of meditation, psychic healings, acupressure, relationship and communication, and massage.

  2. Mutations Related to Antiretroviral Resistance Identified by Ultra-Deep Sequencing in HIV-1 Infected Children under Structured Interruptions of HAART

    PubMed Central

    Vazquez-Guillen, Jose Manuel; Palacios-Saucedo, Gerardo C.; Rivera-Morales, Lydia G.; Garcia-Campos, Jorge; Ortiz-Lopez, Rocio; Noguera-Julian, Marc; Paredes, Roger; Vielma-Ramirez, Herlinda J.; Ramirez, Teresa J.; Chavez-Garcia, Marcelino; Lopez-Guillen, Paulo; Briones-Lara, Evangelina; Sanchez-Sanchez, Luz M.; Vazquez-Martinez, Carlos A.; Rodriguez-Padilla, Cristina

    2016-01-01

    Although Structured Treatment Interruptions (STI) are currently not considered an alternative strategy for antiretroviral treatment, their true benefits and limitations have not been fully established. Some studies suggest the possibility of improving the quality of life of patients with this strategy; however, the information that has been obtained corresponds mostly to studies conducted in adults, with a lack of knowledge about its impact on children. Furthermore, mutations associated with antiretroviral resistance could be selected due to sub-therapeutic levels of HAART at each interruption period. Genotyping methods to determine the resistance profiles of the infecting viruses have become increasingly important for the management of patients under STI, thus low-abundance antiretroviral drug-resistant mutations (DRM’s) at levels under limit of detection of conventional genotyping (<20% of quasispecies) could increase the risk of virologic failure. In this work, we analyzed the protease and reverse transcriptase regions of the pol gene by ultra-deep sequencing in pediatric patients under STI with the aim of determining the presence of high- and low-abundance DRM’s in the viral rebounds generated by the STI. High-abundance mutations in protease and high- and low-abundance mutations in reverse transcriptase were detected but no one of these are directly associated with resistance to antiretroviral drugs. The results could suggest that the evaluated STI program is virologically safe, but strict and carefully planned studies, with greater numbers of patients and interruption/restart cycles, are still needed to evaluate the selection of DRM’s during STI. PMID:26807922

  3. Screening and diagnosis for HIV

    MedlinePlus

    HIV testing; HIV screening; HIV screening test; HIV confirmatory test ... Task Force. Final Update Summary: Human Immunodeficiency Virus (HIV) Infection: Screening. July 2015. www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/ ...

  4. Near full-length genome sequence of a novel HIV-1 recombinant form (CRF01_AE/B) detected among men who have sex with men in Jilin Province, China.

    PubMed

    Li, Xingguang; Feng, Yi; Yang, Yao; Chen, Yanli; Guo, Qi; Sun, Liuyan; Zang, Xihui; Xing, Hui; Shao, Yiming

    2014-07-01

    We report here a novel HIV-1 recombinant form (CRF01_AE/B) detected from a comprehensive HIV-1 molecular epidemiologic study among men who have sex with men (MSM) in Jilin province of northeastern China. The near full-length genome (NFLG) analyses showed that the novel HIV-1 recombinant isolate (JL.RF07) was composed of CRF01_AE cluster 5 (northeastern China origin) and subtype B (U.S. and European origin), with six recombinant breakpoints observed in the pol, vif, tat, rev, and env gene regions. To the best of our knowledge, this is the first detection of a novel HIV-1 recombinant form (CRF01_AE/B) in Jilin, which may indicate an active transmission network of HIV-1 infection among MSM in the region. Further studies of the molecular epidemiology of the HIV-1 epidemic among MSM in northeastern China are necessary to gain a fuller understanding of the transmission network and potential public health impact of HIV-1 among MSM in this region.

  5. Towards modeling DNA sequences as automata

    NASA Astrophysics Data System (ADS)

    Burks, Christian; Farmer, Doyne

    1984-01-01

    We seek to describe a starting point for modeling the evolution and role of DNA sequences within the framework of cellular automata by discussing the current understanding of genetic information storage in DNA sequences. This includes alternately viewing the role of DNA in living organisms as a simple scheme and as a complex scheme; a brief review of strategies for identifying and classifying patterns in DNA sequences; and finally, notes towards establishing DNA-like automata models, including a discussion of the extent of experimentally determined DNA sequence data present in the database at Los Alamos.

  6. HIV Testing

    MedlinePlus

    ... the right way, every day. If you have health insurance, your insurer is required to cover some medicines ... to treat HIV. If you don’t have health insurance, or you’re unable to afford your co- ...

  7. Recent UCN source developments at Los Alamos

    SciTech Connect

    Seestrom, S.J.; Anaya, J.M.; Bowles, T.J.

    1998-12-01

    The most intense sources of ultra cold neutrons (UCN) have bee built at reactors where the high average thermal neutron flux can overcome the low UCN production rate to achieve usable densities of UCN. At spallation neutron sources the average flux available is much lower than at a reactor, though the peak flux can be comparable or higher. The authors have built a UCN source that attempts to take advantage of the high peak flux available at the short pulse spallation neutron source at the Los Alamos Neutron Science Center (LANSCE) to generate a useful number of UCN. In the source UCN are produced by Doppler-shifted Bragg scattering of neutrons to convert 400-m/s neutrons down into the UCN regime. This source was initially tested in 1996 and various improvements were made based on the results of the 1996 running. These improvements were implemented and tested in 1997. In sections 2 and 3 they discuss the improvements that have been made and the resulting source performance. Recently an even more interesting concept was put forward by Serebrov et al. This involves combining a solid Deuterium UCN source, previously studied by Serebrov et al., with a pulsed spallation source to achieve world record UCN densities. They have initiated a program of calculations and measurements aimed at verifying the solid Deuterium UCN source concept. The approach has been to develop an analytical capability, combine with Monte Carlo calculations of neutron production, and perform benchmark experiments to verify the validity of the calculations. Based on the calculations and measurements they plan to test a modified version of the Serebrov UCN factory. They estimate that they could produce over 1,000 UCN/cc in a 15 liter volume, using 1 {micro}amp of 800 MeV protons for two seconds every 500 seconds. They will discuss the result UCN production measurements in section 4.

  8. Waste characterization at Los Alamos National Laboratory

    SciTech Connect

    Corpion, J.C.; Grieggs, A.R.

    1991-01-01

    Most industries generate limited types of solid wastes of a result of their manufacturing processes. The Los Alamos National Laboratory (LANL), a research and development facility, generates a large variety of solid wastes, some exotic. Over 50,000 distinct waste streams are currently generated in the 43 square mile area defining LANL. These wastes include refuse, medical, infectious, hazardous, radioactive, and mixed wastes. LANL is subject to federal and State oversight on matters concerning management of solid wastes. In order to assure regulatory agencies such as the New Mexico Environment Department (NMED) and the US Environmental Protection Agency (EPA) that the Laboratory is properly managing and disposing all solid wastes. LANL has undertaken an extensive waste characterization program to identify sources and ultimate disposition of all solid wastes. Given the number of solid waste streams expected, LANL has taken a two-pronged approach to characterizing wastes: (a) physical identification of all sources of solid wastes including interviews with waste generators; and (b) characterization of wastes from the point of generation. The former approach consists of canvassing all structures within the LANL complex, interviewing waste generators, and identifying sources of waste generation. Data gathered by these interviews are compiled in a database in order to identify the types and rates of waste generation and correct mismanagement of wastes identified during the interviews. The latter approach consists of characterizing all solid wastes which are controlled administratively or subject to stricter controls than municipal solid wastes (i.e., infectious, hazardous, radioactive, and mixed wastes). This characterization forms the basis by which LANL will manage solid waste in accordance to NMED/EPA regulations and US Department of Energy Orders. 8 refs., 3 figs.

  9. HIV classification using coalescent theory

    SciTech Connect

    Zhang, Ming; Letiner, Thomas K; Korber, Bette T

    2008-01-01

    Algorithms for subtype classification and breakpoint detection of HIV-I sequences are based on a classification system of HIV-l. Hence, their quality highly depend on this system. Due to the history of creation of the current HIV-I nomenclature, the current one contains inconsistencies like: The phylogenetic distance between the subtype B and D is remarkably small compared with other pairs of subtypes. In fact, it is more like the distance of a pair of subsubtypes Robertson et al. (2000); Subtypes E and I do not exist any more since they were discovered to be composed of recombinants Robertson et al. (2000); It is currently discussed whether -- instead of CRF02 being a recombinant of subtype A and G -- subtype G should be designated as a circulating recombination form (CRF) nd CRF02 as a subtype Abecasis et al. (2007); There are 8 complete and over 400 partial HIV genomes in the LANL-database which belong neither to a subtype nor to a CRF (denoted by U). Moreover, the current classification system is somehow arbitrary like all complex classification systems that were created manually. To this end, it is desirable to deduce the classification system of HIV systematically by an algorithm. Of course, this problem is not restricted to HIV, but applies to all fast mutating and recombining viruses. Our work addresses the simpler subproblem to score classifications of given input sequences of some virus species (classification denotes a partition of the input sequences in several subtypes and CRFs). To this end, we reconstruct ancestral recombination graphs (ARG) of the input sequences under restrictions determined by the given classification. These restritions are imposed in order to ensure that the reconstructed ARGs do not contradict the classification under consideration. Then, we find the ARG with maximal probability by means of Markov Chain Monte Carlo methods. The probability of the most probable ARG is interpreted as a score for the classification. To our

  10. Preventing HIV with Medicine

    MedlinePlus

    ... information in Spanish ( en español ) Preventing HIV with medicine Get medicine right after you are exposed to ... to top More information on Preventing HIV with medicine Explore other publications and websites National HIV and ...

  11. Older People and HIV

    MedlinePlus

    ... common than they were before the use of anti-HIV drugs. It is difficult to know what is causing mental problems in older people with HIV. Is it normal aging, or is it HIV disease? Research studies have ...

  12. HIV/AIDS

    MedlinePlus

    HIV infection; Infection - HIV; Human immunodeficiency virus; Acquired immune deficiency syndrome ... Symptoms related to acute HIV infection (when a person is first infected) can be similar to the flu or other viral illnesses. They include: Fever and ...

  13. How HIV Causes AIDS

    MedlinePlus

    ... Share this: Main Content Area How HIV Causes AIDS HIV destroys CD4 positive (CD4+) T cells, which ... and disease, ultimately resulting in the development of AIDS. Most people who are infected with HIV can ...

  14. HIV/AIDS Basics

    MedlinePlus

    ... Enter ZIP code or city Follow Act Against AIDS Act Against AIDS @talkHIV Act Against AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets HIV/ ...

  15. HIV-AIDS Connection

    MedlinePlus

    ... Marketing Share this: Main Content Area The HIV-AIDS Connection AIDS was first recognized in 1981 and ... is there overwhelming scientific consensus that HIV causes AIDS? Before HIV infection became widespread in the human ...

  16. HIV/AIDS

    MedlinePlus

    ... at risk for serious infections and certain cancers. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most often spreads through unprotected sex with ...

  17. HIV/AIDS

    MedlinePlus

    ... HIV infections. HIV infection is often diagnosed through rapid diagnostic tests (RDTs), which detect the presence or absence of ... accuracy. It is important to note that serological tests detect antibodies produced ... pathogens, rather than direct detection of HIV itself. Most ...

  18. HIV testing in India.

    PubMed

    Tripathy, Srikanth; Pereira, Michael; Tripathy, Sriram Prasad

    2012-06-01

    The National AIDS Control Organization (NACO) has initiated programs for HIV/AIDS control in India. Algorithms for HIV testing have been developed for India. NACO programs have resulted in HIV situation improving over the last decade.

  19. HIV migration between blood plasma and cellular subsets before and after HIV therapy.

    PubMed

    Choi, Jun Yong; Chaillon, Antoine; Oh, Jin Ok; Ahn, Jin Young; Ann, Hae Won; Jung, In Young; Ahn, Mi-Young; Jeon, Yong Duk; Ku, Nam Su; Smith, Davey M; Kim, June Myung

    2016-04-01

    The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence-activated cell sorter. HIV-1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77-100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells. PMID:26348372

  20. HIV migration between blood plasma and cellular subsets before and after HIV therapy.

    PubMed

    Choi, Jun Yong; Chaillon, Antoine; Oh, Jin Ok; Ahn, Jin Young; Ann, Hae Won; Jung, In Young; Ahn, Mi-Young; Jeon, Yong Duk; Ku, Nam Su; Smith, Davey M; Kim, June Myung

    2016-04-01

    The cellular source of HIV RNA circulating in blood plasma remains unclear. Here, we investigated whether sequence analysis of HIV RNA populations circulating before combination antiretroviral therapy (cART) and HIV DNA populations in cellular subsets (CS) after cART could identify the cellular sources of circulating HIV RNA. Blood was collected from five subjects at cART initiation and again 6 months later. Naïve CD4+ T cells, resting central memory and effector memory CD4+ T cells, activated CD4+ T cells, monocytes, and natural killer cells were sorted using a fluorescence-activated cell sorter. HIV-1 env C2V3 sequences from HIV RNA in blood plasma and HIV DNA in CSs were generated using single genome sequencing. Sequences were evaluated for viral compartmentalization (Fst test) and migration events (MEs; Slatkin Maddison and cladistic measures) between blood plasma and each CS. Viral compartmentalization was observed in 88% of all cellular subset comparisons (range: 77-100% for each subject). Most observed MEs were directed from blood plasma to CSs (52 MEs, 85.2%). In particular, there was only viral movement from plasma to NK cells (15 MEs), monocytes (seven MEs), and naïve cells (five ME). We observed a total of nine MEs from activated CD4 cells (2/9 MEs), central memory T cells (3/9 MEs), and effector memory T cells (4/9 MEs) to blood plasma. Our results revealed that the HIV RNA population in blood plasma plays an important role in seeding various cellular reservoirs and that the cellular source of the HIV RNA population is activated central memory and effector memory T cells.

  1. Broad activation of latent HIV-1 in vivo.

    PubMed

    Barton, Kirston; Hiener, Bonnie; Winckelmann, Anni; Rasmussen, Thomas Aagaard; Shao, Wei; Byth, Karen; Lanfear, Robert; Solomon, Ajantha; McMahon, James; Harrington, Sean; Buzon, Maria; Lichterfeld, Mathias; Denton, Paul W; Olesen, Rikke; Østergaard, Lars; Tolstrup, Martin; Lewin, Sharon R; Søgaard, Ole Schmeltz; Palmer, Sarah

    2016-01-01

    The 'shock and kill' approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4(+) T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically diverse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1. PMID:27605062

  2. Broad activation of latent HIV-1 in vivo

    PubMed Central

    Barton, Kirston; Hiener, Bonnie; Winckelmann, Anni; Rasmussen, Thomas Aagaard; Shao, Wei; Byth, Karen; Lanfear, Robert; Solomon, Ajantha; McMahon, James; Harrington, Sean; Buzon, Maria; Lichterfeld, Mathias; Denton, Paul W.; Olesen, Rikke; Østergaard, Lars; Tolstrup, Martin; Lewin, Sharon R.; Søgaard, Ole Schmeltz; Palmer, Sarah

    2016-01-01

    The ‘shock and kill' approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4+ T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically diverse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1. PMID:27605062

  3. Broad activation of latent HIV-1 in vivo.

    PubMed

    Barton, Kirston; Hiener, Bonnie; Winckelmann, Anni; Rasmussen, Thomas Aagaard; Shao, Wei; Byth, Karen; Lanfear, Robert; Solomon, Ajantha; McMahon, James; Harrington, Sean; Buzon, Maria; Lichterfeld, Mathias; Denton, Paul W; Olesen, Rikke; Østergaard, Lars; Tolstrup, Martin; Lewin, Sharon R; Søgaard, Ole Schmeltz; Palmer, Sarah

    2016-09-08

    The 'shock and kill' approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4(+) T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically diverse, indicating activation of transcription from an extensive range of proviruses. Defective sequences are more frequently found in CA HIV-1 RNA than in HIV-1 DNA, which has implications for developing an accurate measure of HIV-1 reservoir size. Our findings provide insights into the effects of panobinostat and vorinostat as LRAs for latent HIV-1.

  4. Population genomics of intrapatient HIV-1 evolution.

    PubMed

    Zanini, Fabio; Brodin, Johanna; Thebo, Lina; Lanz, Christa; Bratt, Göran; Albert, Jan; Neher, Richard A

    2015-01-01

    Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. The data can be accessed and explored via an interactive web application. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100 bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity. PMID:26652000

  5. Population genomics of intrapatient HIV-1 evolution.

    PubMed

    Zanini, Fabio; Brodin, Johanna; Thebo, Lina; Lanz, Christa; Bratt, Göran; Albert, Jan; Neher, Richard A

    2015-01-01

    Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. The data can be accessed and explored via an interactive web application. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100 bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity.

  6. Interplay between HIV-1 and Host Genetic Variation: A Snapshot into Its Impact on AIDS and Therapy Response.

    PubMed

    Sampathkumar, Raghavan; Shadabi, Elnaz; Luo, Ma

    2012-01-01

    As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response. PMID:22666249

  7. Interplay between HIV-1 and Host Genetic Variation: A Snapshot into Its Impact on AIDS and Therapy Response

    PubMed Central

    Sampathkumar, Raghavan; Shadabi, Elnaz; Luo, Ma

    2012-01-01

    As of February 2012, 50 circulating recombinant forms (CRFs) have been reported for HIV-1 while one CRF for HIV-2. Also according to HIV sequence compendium 2011, the HIV sequence database is replete with 414,398 sequences. The fact that there are CRFs, which are an amalgamation of sequences derived from six or more subtypes (CRF27_cpx (cpx refers to complex) is a mosaic with sequences from 6 different subtypes besides an unclassified fragment), serves as a testimony to the continual divergent evolution of the virus with its approximate 1% per year rate of evolution, and this phenomena per se poses tremendous challenge for vaccine development against HIV/AIDS, a devastating disease that has killed 1.8 million patients in 2010. Here, we explore the interaction between HIV-1 and host genetic variation in the context of HIV/AIDS and antiretroviral therapy response. PMID:22666249

  8. The Molecular Characterization of Intestinal Explant HIV Infection Using Polymerase Chain Reaction-Based Techniques

    PubMed Central

    Janocko, Laura; Althouse, Andrew D.; Brand, Rhonda M.; Cranston, Ross D.

    2015-01-01

    Abstract The ex vivo mucosal explant model is frequently used to test the efficacy of microbicides that have the potential for preventing HIV-1 transmission. The conventional assessment of product efficacy has been the extent of HIV-1 p24 suppression in supernatant fluids sampled up to day 14 after HIV-1 challenge ex vivo. The purpose of this study was to determine if measurement of HIV-1 nucleic acids by real-time PCR and HIV-1 integration by Alu-gag PCR provides advantages with regard to monitoring HIV-1 infection in explants. Rectal biopsies from HIV-1-negative individuals were challenged with 1 × 105 virions/ml of HIV-1BaL or HIV-1CH077 ex vivo. HIV-1 RNA and HIV-1 p24 in supernatant fluids and HIV-1 nucleic acids and integrated provirus in individual biopsies were measured at days 1–14 after infection. HIV-1 RNA and proviral DNA were measured by quantitative real-time PCR (qRT-PCR) while integrated virus was detected by Alu-gag PCR. Real-time PCR assays detecting HIV-1 DNA and RNA performed similarly provided that the infecting virus sequences were a good match with the sequences of the assay primers and probes. Increased HIV-1 nucleic acid levels and DNA integration were measurable on days 11 and 14 after infection. The magnitude of explant infection was similar after challenge with HIV-1BaL and HIV-1CH077, although the trajectory of infection was delayed in the HIV-1CH077-infected biopsies. In the majority of experiments, qRT-PCR did not appreciably shorten the time necessary to detect evidence of HIV-1 infection. PMID:26214703

  9. 1993 Northern goshawk inventory on portions of Los Alamos National Laboratory, Los Alamos, NM. Final report

    SciTech Connect

    Sinton, D.T.; Kennedy, P.L.

    1994-06-01

    Northern goshawks (Accipiter gentilis) (hereafter referred to as goshawk) is a large forest dwelling hawk. Goshawks may be declining in population and reproduction in the southwestern United States. Reasons for the possible decline in goshawk populations include timber harvesting resulting in the loss of nesting habitat, toxic chemicals, and the effects of drought, fire, and disease. Thus, there is a need to determine their population status and assess impacts of management activities in potential goshawk habitat. Inventory for the goshawk was conducted on 2,254 ha of Los Alamos National Laboratory (LANL) to determine the presence of nesting goshawks on LANL lands. This information can be incorporated into LANL`s environmental management program. The inventory was conducted by Colorado State University personnel from May 12 to July 30, 1993. This report summarizes the results of this inventory.

  10. Integrated review software advances at Los Alamos

    SciTech Connect

    Klosterbuer, S. F.; Michel, K. D.; Betts, S. E.; Determan, J. C.; Longo, J. F.; Parker, R. F.; Pelowitz, D. G.; Rothrock, R. B.; Schneider, C. M.; Nordquist, H. M.

    2004-01-01

    Since 1988, Los Alamos National Laboratory (LANL) has been developing software for unattended monitoring systems. These systems are composed of three categories of software: acquisition, collection and review. The data acquisition software is contained in modular instrumentation distributed throughout facilities to continuously acquire data from devices ranging from radiation detectors to cameras to binary switches. The data collection software runs on computers connected to the instruments and offloads and stores the acquired data. The review software enables the end user to quickly and easily examine the data collected from these different systems and compare the results to declared operator activities. This paper addresses the review software. The original standalone review software processed only radiation data. This software was expanded to include new programs (tools) to display and correlate video and operator declarations and added an interface to the standard neutron coincidence counter analysis program. This expanded review software containing multiple review tools is referred to collectively as the Integrated Review Software (IRS). The IRS continues to expand and evolve. Two primary IRS developments will be described in this paper. First, the IRS was expanded to include review tools to display and analyze new data types. Position Review was developed to display Global Positioning System (GPS) location data to aid in tracking radiation movements. Isotopic Review is being developed to provide a link to the standard gamma isotopic analysis software. In addition significant enhancements are being added to the existing review tools such as Operator Review, Radiation Review and Digital Video Review. A second IRS development is to produce standardized components with published interfaces enabling other parties to produce custom components that plug into review software. It is anticipated that there will be four primary types of components that could be

  11. Nearly Finished Genomes Produced Using Gel Microdroplet Culturing (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    ScienceCinema

    Fitzsimmons, Michael [LANL

    2016-07-12

    Michael Fitzsimmons from Los Alamos National Laboratory gives a talk titled "Nearly Finished Genomes Produced Using Gel Microdroplet Culturing" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  12. Nearly Finished Genomes Produced Using Gel Microdroplet Culturing (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

    SciTech Connect

    Fitzsimmons, Michael

    2012-06-01

    Michael Fitzsimmons from Los Alamos National Laboratory gives a talk titled "Nearly Finished Genomes Produced Using Gel Microdroplet Culturing" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

  13. Water Supply at Los Alamos 1998-2001

    SciTech Connect

    Richard J. Koch; David B. Rogers

    2003-03-01

    For the period 1998 through 2001, the total water used at Los Alamos from all sources ranged from 1325 million gallons (Mg) in 1999 to 1515 Mg in 2000. Groundwater production ranged from 1323 Mg in 1999 to 1506 Mg in 2000 from the Guaje, Pajarito, and Otowi fields. Nonpotable surface water used from Los Alamos reservoir ranged from zero gallons in 2001 to 9.3 Mg in 2000. For years 1998 through 2001, over 99% of all water used at Los Alamos was groundwater. Water use by Los Alamos National Laboratory (LANL) between 1998 and 2001 ranged from 379 Mg in 2000 to 461 Mg in 1998. The LANL water use in 2001 was 393 Mg or 27% of the total water use at Los Alamos. Water use by Los Alamos County ranged from 872 Mg in 1999 to 1137 Mg in 2000, and averaged 1006 Mg/yr. Four new replacement wells in the Guaje field (G-2A, G-3A, G-4A, and G-5A) were drilled in 1998 and began production in 1999; with existing well G-1A, the Guaje field currently has five producing wells. Five of the old Guaje wells (G-1, G-2, G-4, G-5, and G-6) were plugged and abandoned in 1999, and one well (G-3) was abandoned but remains as an observation well for the Guaje field. The long-term water level observations in production and observation (test) wells at Los Alamos are consistent with the formation of a cone of depression in response to water production. The water level decline is gradual and at most has been about 0.7 to 2 ft per year for production wells and from 0.4 to 0.9 ft/yr for observation (test) wells. The largest water level declines have been in the Guaje field where nonpumping water levels were about 91 ft lower in 2001 than in 1951. The initial water levels of the Guaje replacement wells were 32 to 57 ft lower than the initial water levels of adjacent original Guaje wells. When production wells are taken off-line for pump replacement or repair, water levels have returned to within about 25 ft of initial static levels within 6 to 12 months. Thus, the water-level trends suggest no adverse

  14. A progress report on UNICOS misuse detection at Los Alamos

    SciTech Connect

    Thompson, J.L.; Jackson, K.A.; Stallings, C.A.; Simmonds, D.D.; Siciliano, C.L.B.; Pedicini, G.A.

    1995-10-01

    An effective method for detecting computer misuse is the automatic monitoring and analysis of on-line user activity. During the past year, Los Alamos enhanced its Network Anomaly Detection and Intrusion Reporter (NADIR) to include analysis of user activity on Los Alamos` UNICOS Crays. In near real-time, NADIR compares user activity to historical profiles and tests activity against expert rules. The expert rules express Los Alamos` security policy and define improper or suspicious behavior. NADIR reports suspicious behavior to security auditors and provides tools to aid in follow-up investigations. This paper describes the implementation to date of the UNICOS component of NADIR, along with the operational experiences and future plans for the system.

  15. Publications of Los Alamos research, 1977-1981

    SciTech Connect

    Sheridan, C.J.; Garcia, C.A.

    1983-03-01

    This bibliography is a compilation of unclassified publications of work done at the Los Alamos National Laboratory for 1977-1981. Papers published in those years are included regardless of when they were actually written. Publications received too late for inclusion in earlier compilations have also been listed. Declassification of previously classified reports is considered to constitute publication. All classified issuances are omitted - even those papers, themselves unclassified, which were published only as part of a classified document. If a paper was published more than once, all places of publication are included. The bibliography includes Los Alamos National Laboratory reports, papers released as non-Laboratory reports, journal articles, books, chapters of books, conference papers either published separately or as part of conference proceedings issued as books or reports, papers published in congressional hearings, theses, and US patents. Publications by Los Alamos authors that are not records of Laboratory-sponsored work are included when the Library becomes aware of them.

  16. HIV epidemiology. The early spread and epidemic ignition of HIV-1 in human populations.

    PubMed

    Faria, Nuno R; Rambaut, Andrew; Suchard, Marc A; Baele, Guy; Bedford, Trevor; Ward, Melissa J; Tatem, Andrew J; Sousa, João D; Arinaminpathy, Nimalan; Pépin, Jacques; Posada, David; Peeters, Martine; Pybus, Oliver G; Lemey, Philippe

    2014-10-01

    Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations.

  17. Water supply at Los Alamos during 1993. Progress report

    SciTech Connect

    Purtymun, W.D.; Stoker, A.K.; McLin, S.G.; Maes, M.N.; Glasco, T.A.

    1995-10-01

    This report summarizes production and aquifer conditions for water wells in the Guaje, Pajarito, and Otowi Well Fields. These wells supplied all of the potable water used for municipal and some industrial purposes in Los Alamos County and the Los Alamos National Laboratory during 1993. The wells in the Los Alamos Well Field were transferred to San Ildefonso Pueblo in 1992. Four of the wells in the Los Alamos Well Field were plugged in 1993. One of the two new wells in the Otowi Well Field became operational in 1993. The spring gallery in Water Canyon supplied nonpotable water for industrial use, while surface water from the Los Alamos Reservoir was diverted for irrigation. In 1993 no water was used from the Guaje Reservoir. Due to the maintenance and operating cost of diverting water from the reservoirs, it is not economically feasible to continue their use for irrigation. This report fulfills some of the requirements of the Los Alamos Groundwater Protection Management Program by documenting use of the groundwater for water supply and providing information hydrologic characteristics of the main aquifer. This report is a joint effort between the Laboratory Water Quality and Hydrology Group and the Utilities Department of Johnson Controls World Services Inc. (JCI). The purpose of this report is to ensure a continuing historical record and to provide guidance for management of water resources in long-range planning for the water supply system. We have issued one summary report for the period of 1947 to 1971 and 22 annual reports that contain the results of our studies of these water supplies. An additional report summarized the hydrology of the main aquifer with reference to future development of groundwater supplies. A report was issued in 1988 that examined the status of wells and future water supply.

  18. The development of the atomic bomb, Los Alamos

    SciTech Connect

    Seidel, R.W.

    1993-11-01

    The historical presentation begins with details of the selection of Los Alamos as the site of the Army installation. Wartime efforts of the Army Corps of Engineers, and scientists to include the leader of Los Alamos, Robert Oppenheimer are presented. The layout and construction of the facilities are discussed. The monumental design requirements of the bombs are discussed, including but not limited to the utilization of the second choice implosion method of detonation, and the production of bomb-grade nuclear explosives. The paper ends with a philosophical discussion on the use of nuclear weapons.

  19. Los Alamos Using Neutrons to Stop Nuclear Smugglers

    ScienceCinema

    Favalli, Andrea; Swinhoe, Martyn

    2016-07-12

    Los Alamos National Laboratory researchers have successfully demonstrated for the first time that laser-generated neutrons can be enlisted as a useful tool in the War on Terror. The international research team used the short-pulse laser at Los Alamos's TRIDENT facility to generate a neutron beam with novel characteristics that interrogated a closed container to confirm the presence and quantity of nuclear material inside. The successful experiment paves the way for creation of a table-top-sized or truck-mounted neutron generator that could be installed at strategic locations worldwide to thwart smugglers trafficking in nuclear materials.

  20. Fifty-one years of Los Alamos Spacecraft

    SciTech Connect

    Fenimore, Edward E.

    2014-09-04

    From 1963 to 2014, the Los Alamos National Laboratory was involved in at least 233 spacecraft. There are probably only one or two institutions in the world that have been involved in so many spacecraft. Los Alamos space exploration started with the Vela satellites for nuclear test detection, but soon expanded to ionospheric research (mostly barium releases), radioisotope thermoelectric generators, solar physics, solar wind, magnetospheres, astrophysics, national security, planetary physics, earth resources, radio propagation in the ionosphere, and cubesats. Here, we present a list of the spacecraft, their purpose, and their launch dates for use during RocketFest

  1. A physicists guide to The Los Alamos Primer

    NASA Astrophysics Data System (ADS)

    Reed, B. Cameron

    2016-11-01

    In April 1943, a group of scientists at the newly established Los Alamos Laboratory were given a series of lectures by Robert Serber on what was then known of the physics and engineering issues involved in developing fission bombs. Serber’s lectures were recorded in a 24 page report titled The Los Alamos Primer, which was subsequently declassified and published in book form. This paper describes the background to the Primer and analyzes the physics contained in its 22 sections. The motivation for this paper is to provide a firm foundation of the background and contents of the Primer for physicists interested in the Manhattan Project and nuclear weapons.

  2. Contributions of chemistry in early day Los Alamos

    SciTech Connect

    Penneman, R.A.; Meade, R.A.

    1990-01-01

    During 1943--1945, the premier physics laboratory in the world was at Los Alamos, but chemistry contributions were vital. Major chemical impacts on the success of the Los Alamos wartime mission included electrochemistry, which found the true melting point of plutonium metal to be hundreds of degrees lower than anticipated. This discovery had profound simplifying effects regarding crucibles to contain molten plutonium and on its production. Other significant chemical contributions involved constant purification of plutonium for reuse, producing carrier-free gamma sources at unprecedented kilo-curie levels, and high polonium work. 8 refs.

  3. Los Alamos Using Neutrons to Stop Nuclear Smugglers

    SciTech Connect

    Favalli, Andrea; Swinhoe, Martyn

    2013-06-03

    Los Alamos National Laboratory researchers have successfully demonstrated for the first time that laser-generated neutrons can be enlisted as a useful tool in the War on Terror. The international research team used the short-pulse laser at Los Alamos's TRIDENT facility to generate a neutron beam with novel characteristics that interrogated a closed container to confirm the presence and quantity of nuclear material inside. The successful experiment paves the way for creation of a table-top-sized or truck-mounted neutron generator that could be installed at strategic locations worldwide to thwart smugglers trafficking in nuclear materials.

  4. Contrasting HIV phylogenetic relationships and V3 loop protein similarities

    SciTech Connect

    Korber, B. Santa Fe Inst., NM ); Myers, G. )

    1992-01-01

    At least five distinct sequence subtypes of HIV-I can be identified from the major centers of the AMS pandemic. While it is too early to tell whether these subtypes are serologically or phenotypically similar or distinct in terms of properties such as pathogenicity and transmissibility, we can begin to investigate their potential for phenotypic divergence at the protein sequence level. Phylogenetic analysis of HIV DNA sequences is being widely used to examine lineages of different viral strains as they evolve and spread throughout the globe. We have identified five distinct HIV-1 subtypes (designated A-E), or clades, based on phylogenetic clustering patterns generated from genetic information from both the gag and envelope (env) genes from a spectrum of international isolates. Our initial observations concerning both HIV-1 and HIV-2 sequences indicate that conserved patterns in protein chemistry may indeed exist across distant lineages. Such patterns in V3 loop amino acid chemistry may be indicative of stable lineages or convergence within this highly variable, though functionally and immunologically critical, region. We think that there may be parallels between the apparently stable HIV-2 V3 lineage and the previously mentioned HIV-1 V3 loops which are very similar at the protein level despite being distant by cladistic analysis, and which do not possess the distinctive positively charged residues. Highly conserved V3 loop protein sequences are also encountered in SIVAGMs and CIVs (chimpanzee viral strains), which do not appear to be pathogenic in their wild-caught natural hosts.

  5. Contrasting HIV phylogenetic relationships and V3 loop protein similarities

    SciTech Connect

    Korber, B. |; Myers, G.

    1992-12-31

    At least five distinct sequence subtypes of HIV-I can be identified from the major centers of the AMS pandemic. While it is too early to tell whether these subtypes are serologically or phenotypically similar or distinct in terms of properties such as pathogenicity and transmissibility, we can begin to investigate their potential for phenotypic divergence at the protein sequence level. Phylogenetic analysis of HIV DNA sequences is being widely used to examine lineages of different viral strains as they evolve and spread throughout the globe. We have identified five distinct HIV-1 subtypes (designated A-E), or clades, based on phylogenetic clustering patterns generated from genetic information from both the gag and envelope (env) genes from a spectrum of international isolates. Our initial observations concerning both HIV-1 and HIV-2 sequences indicate that conserved patterns in protein chemistry may indeed exist across distant lineages. Such patterns in V3 loop amino acid chemistry may be indicative of stable lineages or convergence within this highly variable, though functionally and immunologically critical, region. We think that there may be parallels between the apparently stable HIV-2 V3 lineage and the previously mentioned HIV-1 V3 loops which are very similar at the protein level despite being distant by cladistic analysis, and which do not possess the distinctive positively charged residues. Highly conserved V3 loop protein sequences are also encountered in SIVAGMs and CIVs (chimpanzee viral strains), which do not appear to be pathogenic in their wild-caught natural hosts.

  6. High recombination potential of subtype A HIV-1.

    PubMed

    Nikolaitchik, Olga; Keele, Brandon; Gorelick, Robert; Alvord, W Gregory; Mazurov, Dmitriy; Pathak, Vinay K; Hu, Wei-Shau

    2015-10-01

    Recombination can assort polymorphic alleles to increase diversity in the HIV-1 population. To better understand the recombination potential of subtype A HIV-1, we generated viruses containing sequences from two variants circulating in Russia and analyzed the polymerase gene (pol) of the recombinants after one round of HIV-1 replication using single-genome sequencing. We observed that recombination occurred throughout pol and could easily assort alleles containing mutations that conferred resistance to currently approved antivirals. We measured the recombination rate in various regions of pol including a G-rich region that has been previously proposed to be a recombination hot spot. Our study does not support a recombination hot spot in this G-rich region. Importantly, of the 58 proviral sequences containing crossover event(s) in pol, we found that each sequence was a unique genotype indicating that recombination is a powerful genetic mechanism in assorting the genomes of subtype A HIV-1 variants.

  7. High Degree of HIV-1 Group M (HIV-1M) Genetic Diversity within Circulating Recombinant Forms: Insight into the Early Events of HIV-1M Evolution

    PubMed Central

    2015-01-01

    ABSTRACT The existence of various highly divergent HIV-1 lineages and of recombination-derived sequence tracts of indeterminate origin within established circulating recombinant forms (CRFs) strongly suggests that HIV-1 group M (HIV-1M) diversity is not fully represented under the current classification system. Here we used a fully exploratory screen for recombination on a set of 480 near-full-length genomes representing the full known diversity of HIV-1M. We decomposed recombinant sequences into their constituent parts and then used maximum-likelihood phylogenetic analyses of this mostly recombination-free data set to identify rare divergent sequence lineages that fall outside the major named HIV-1M taxonomic groupings. We found that many of the sequence fragments occurring within CRFs (including CRF04_cpx, CRF06_cpx, CRF11_cpx, CRF18_cpx, CRF25_cpx, CRF27_cpx, and CRF49_cpx) are in fact likely derived from divergent unclassified parental lineages that may predate the current subtypes, even though they are presently identified as derived from currently defined HIV-1M subtypes. Our evidence suggests that some of these CRFs are descended predominantly from what were or are major previously unidentified HIV-1M lineages that were likely epidemiologically relevant during the early stages of the HIV-1M epidemic. The restriction of these divergent lineages to the Congo basin suggests that they were less infectious and/or simply not present at the time and place of the initial migratory wave that triggered the global epidemic. IMPORTANCE HIV-1 group M (HIV-1M) likely spread to the rest of the world from the Congo basin in the mid-1900s (N. R. Faria et al., Science 346:56–61, 2014, http://dx.doi.org/10.1126/science.1256739) and is today the principal cause of the AIDS pandemic. Here, we show that large sequence fragments from several HIV-1M circulating recombinant forms (CRFs) are derived from divergent parental lineages that cannot reasonably be classified within the

  8. Needs assessment for fire department services and resources for the Los Alamos National Laboratory, Los Alamos, New Mexico. Final report

    SciTech Connect

    1995-11-15

    This report has been developed in response to a request from the Los Alamos National Laboratory (LANL) to evaluate the need for fire department services so as to enable the Laboratory to plan effective fire protection and thereby: meet LANL`s regulatory and contractual obligations; interface with the Department of Energy (DOE) and other agencies on matters relating to fire and emergency services; and ensure appropriate protection of the community and environment. This study is an outgrowth of the 1993 Fire Department Needs Assessment (prepared for DOE) but is developed from the LANL perspective. Input has been received from cognizant and responsible representatives at LANL, DOE, Los Alamos County (LAC) and the Los Alamos Fire Department (LAFD).

  9. HIV Structural Database

    National Institute of Standards and Technology Data Gateway

    SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

  10. HIV and AIDS

    MedlinePlus

    ... I Help a Friend Who Cuts? HIV and AIDS KidsHealth > For Teens > HIV and AIDS Print A A A Text Size What's in ... in human history. HIV causes a condition called acquired immunodeficiency syndrome — better known as AIDS . HIV destroys a type ...

  11. A survey of macromycete diversity at Los Alamos National Laboratory, Bandelier National Monument, and Los Alamos County; A preliminary report

    SciTech Connect

    Jarmie, N.; Rogers, F.J.

    1997-11-01

    The authors have completed a 5-year survey (1991--1995) of macromycetes found in Los Alamos County, Los Alamos National Laboratory, and Bandelier National Monument. The authors have compiled a database of 1,048 collections, their characteristics, and identifications. The database represents 123 (98%) genera and 175 (73%) species reliably identified. Issues of habitat loss, species extinction, and ecological relationships are addressed, and comparisons with other surveys are made. With this baseline information and modeling of this baseline data, one can begin to understand more about the fungal flora of the area.

  12. jpHMM at GOBICS: a web server to detect genomic recombinations in HIV-1.

    PubMed

    Zhang, Ming; Schultz, Anne-Kathrin; Calef, Charles; Kuiken, Carla; Leitner, Thomas; Korber, Bette; Morgenstern, Burkhard; Stanke, Mario

    2006-07-01

    Detecting recombinations in the genome sequence of human immunodeficiency virus (HIV-1) is crucial for epidemiological studies and for vaccine development. Herein, we present a web server for subtyping and localization of phylogenetic breakpoints in HIV-1. Our software is based on a jumping profile Hidden Markov Model (jpHMM), a probabilistic generalization of the jumping-alignment approach proposed by Spang et al. The input data for our server is a partial or complete genome sequence from HIV-1; our tool assigns regions of the input sequence to known subtypes of HIV-1 and predicts phylogenetic breakpoints. jpHMM is available online at http://jphmm.gobics.de/.

  13. Secondary HIV prevention.

    PubMed

    Temoshok, L R; Frerichs, R R

    1998-06-01

    Primary HIV prevention, preventing HIV exposure among uninfected persons, has been the focus of much attention. However, secondary HIV prevention, preventing HIV transmission from infected people to their uninfected contacts, has not received as much interest or attention from HIV researchers, clinicians, and policymakers. The concept of secondary HIV prevention, as distinguished from primary prevention, is clarified, and the current and future strategies to further secondary HIV prevention efforts are explored. Secondary prevention strategies can be incorporated into comprehensive programs and result in shifts in attitudes and behaviors. This could reduce the size of the epidemic, while also benefiting the individual and his or her close relationships.

  14. Differential regulation of human immunodeficiency viruses (HIVs): a specific regulatory element in HIV-2 responds to stimulation of the T-cell antigen receptor.

    PubMed Central

    Markovitz, D M; Hannibal, M; Perez, V L; Gauntt, C; Folks, T M; Nabel, G J

    1990-01-01

    The human immunodeficiency viruses (HIVs) types 1 and 2 have similar genetic organization but differ significantly in nucleic acid sequence. Although infection by either agent leads to symptoms of immunodeficiency, recent studies suggest potential differences in the time course and severity of these diseases. In this report, the transcriptional regulation and induction of these retroviruses were analyzed. We report that the regulation of HIV-2 differs from that of HIV-1: a distinct T-cell activation pathway, triggering of the CD3 component of the T-cell receptor complex, stimulates HIV-2 but not HIV-1 gene expression. The response to T-cell receptor stimulation in HIV-2 is mediated partly by an upstream regulatory element, termed CD3R, which is recognized by a sequence-specific DNA binding protein, NF-CD3R. Jurkat T leukemia cell lines containing HIV-2 provirus also showed increased viral replication after stimulation of the T-cell receptor complex, in contrast to HIV-1. These findings suggest that transcriptional regulation and induction of HIV-2 differ from HIV-1 and raise the possibility that different cofactors contribute to the activation of HIV-1- and HIV-2-associated AIDS. Images PMID:2147512

  15. Monitoring Sensitive Bat Species at Los Alamos National Laboratory

    SciTech Connect

    Schoenberg, Kari M.

    2014-01-15

    Bats play a critical role in ecosystems and are vulnerable to disturbance and disruption by human activities. In recent decades, bat populations in the United States and elsewhere have decreased tremendously. There are 47 different species of bat in the United States and 28 of these occur in New Mexico with 15 different species documented at the Los Alamos National Laboratory (LANL) and surrounding areas. Euderma maculatum(the spotted bat) is listed as “threatened” by the state of New Mexico and is known to occur at LANL. Four other species of bats are listed as “sensitive” and also occur here. In 1995, a four year study was initiated at LANL to assess the status of bat species of concern, elucidate distribution and relative abundance, and obtain information on roosting sites. There have been no definitive studies since then. Biologists in the Environmental Protection Division at LANL initiated a multi-year monitoring program for bats in May 2013 to implement the Biological Resources Management Plan. The objective of this ongoing study is to monitor bat species diversity and seasonal activity over time at LANL. Bat species diversity and seasonal activity were measured using an acoustic bat detector, the Pettersson D500X. This ultrasound recording unit is intended for long-term, unattended recording of bat and other high frequency animal calls. During 2013, the detector was deployed at two locations around LANL. Study sites were selected based on proximity to water where bats may be foraging. Recorded bat calls were analyzed using Sonobat, software that can help determine specific species of bat through their calls. A list of bat species at the two sites was developed and compared to lists from previous studies. Species diversity and seasonal activity, measured as the number of call sequences recorded each month, were compared between sites and among months. A total of 17,923 bat calls were recorded representing 15 species. Results indicate that there is a

  16. Side Effects of HIV Medicines: HIV and Lactic Acidosis

    MedlinePlus

    ... HIV medicines. All HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class may cause lactic acidosis, but ... some HIV medicines. HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class can cause the body to ...

  17. Technical manpower needs and resources at Los Alamos National Laboratory

    SciTech Connect

    Freese, K.B.

    1984-01-01

    The Los Alamos National Laboratory has begun a program to share its scientific and technological expertise with students and teachers in the surrounding area. The goal of the Laboratory's Educational Outreach Program is to stimulate an awareness of professional opportunities in the sciences and engineering.

  18. Direct-current proton-beam measurements at Los Alamos

    SciTech Connect

    Sherman, Joseph; Stevens, Ralph R.; Schneider, J. David; Zaugg, Thomas

    1995-09-15

    Recently, a CW proton accelerator complex was moved from Chalk River Laboratories (CRL) to Los Alamos National Laboratory. This includes a 50-keV dc proton injector with a single-solenoid low-energy beam transport system (LEBT) and a CW 1.25-MeV, 267-MHz radiofrequency quadrupole (RFQ). The move was completed after CRL had achieved 55-mA CW operation at 1.25 MeV using 250-kW klystrode tubes to power the RFQ. These accelerator components are prototypes for the front end of a CW linac required for an accelerator-driven transmutation linac, and they provide early confirmation of some CW accelerator components. The injector (ion source and LEBT) and emittance measuring unit are installed and operational at Los Alamos. The dc microwave ion source has been operated routinely at 50-keV, 75-mA hydrogen-ion current. This ion source has demonstrated very good discharge and H2 gas efficiencies, and sufficient reliability to complete CW RFQ measurements at CRL. Proton fraction of 75% has been measured with 550-W discharge power. This high proton fraction removes the need for an analyzing magnet. Proton LEBT emittance measurements completed at Los Alamos suggest that improved transmission through the RFQ may be achieved by increasing the solenoid focusing current. Status of the final CW RFQ operation at CRL and the installation of the RFQ at Los Alamos will be given.

  19. Direct-current proton-beam measurements at Los Alamos

    SciTech Connect

    Sherman, J.; Stevens, R.R.; Schneider, J.D.; Zaugg, T.

    1994-08-01

    Recently, a CW proton accelerator complex was moved from Chalk River Laboratories (CRL) to Los Alamos National Laboratory. This includes a 50-keV dc proton injector with a single-solenoid low-energy beam transport system (LEBT) and a CW 1.25-MeV, 267-MHz radiofrequency quadrupole (RFQ). The move was completed after CRL had achieved 55-mA CW operation at 1.25 MeV using 250-kW klystrode tubes to power the RFQ. These accelerator components are prototypes for the front end of a CW linac required for an accelerator-driven transmutation linac, and they provide early confirmation of some CW accelerator components. The injector (ion source and LEBT) and emittance measuring unit are installed and operational at Los Alamos. The dc microwave ion source has been operated routinely at 50-keV, 75-mA hydrogen-ion current. This ion source has demonstrated very good discharge and H{sub 2} gas efficiencies, and sufficient reliability to complete CW RFQ measurements at CRL. Proton fraction of 75% has been measured with 550-W discharge power. This high proton fraction removes the need for an analyzing magnet. Proton LEBT emittance measurements completed at Los Alamos suggest that improved transmission through the RFQ may be achieved by increasing the solenoid focusing current. Status of the final CW RFQ operation at CRL and the installation of the RFQ at Los Alamos is given.

  20. Summary of environmental surveillance at Los Alamos during 1995

    SciTech Connect

    1996-10-01

    Linking the Rio Grande Valley and the Jemez Mountains, New Mexico`s Pajarito Plateau is home to a world-class scientific institution. Los Alamos National Laboratory (or the Laboratory), managed by the Regents of the University of California, is a government-owned, Department of Energy-supervised complex investigating all areas of modern science for the purposes of national defense, health, conservation, and ecology. The Laboratory was founded in 1943 as part of the Manhattan Project, whose members assembled to create the first nuclear weapon. Occupying the campus of the Los Alamos Ranch School, American and British scientists gathered on the isolated mesa tops to harness recently discovered nuclear power with the hope of ending World War II. In July 1945, the initial objective of the Laboratory, a nuclear device, was achieved in Los Alamos and tested in White Sands, New Mexico. Today the Laboratory continues its role in defense, particularly in nuclear weapons, including developing methods for safely handling weapons and managing waste. For the past twenty years, the Laboratory has published an annual environmental report. This pamphlet offers a synopsis that briefly explains important concepts, such as radiation and provides a summary of the monitoring results and regulatory compliance status that are explained at length in the document entitled Environmental Surveillance at Los Alamos during 1995.

  1. Mercury: The Los Alamos ICF KrF laser system

    SciTech Connect

    Czuchlewski, S.J.; York, G.W.; Bigio, I.J.; Brucker, J.; Hanson, D.; Honig, E.M.; Kurnit, N.; Leland, W.; McCown, A.W.; McLeod, J.; Rose, E.; Thomas, S.; Thompson, D.

    1993-01-19

    The Mercury KrF laser facility at Los Alamos is being built with the benefit of lessons learned from the Aurora system. An increased understanding of KrF laser engineering, and the designed implementation of system flexibility, will permit Mercury to serve as a tested for a variety of advanced KrF technology concepts.

  2. The Controlled-Air Incinerator at Los Alamos

    SciTech Connect

    Newmyer, J.N.

    1994-04-01

    The Controlled-Air Incinerator (CAI) at Los Alamos is being modified and upgraded to begin routine operations treating low-level mixed waste (LLMW), radioactively contaminated polychlorinated biphenyl (PCB) wastes, low-level liquid wastes, and possibly transuranic (TRU) wastes. This paper describes those modifications. Routine waste operations should begin in late FY95.

  3. The Los Alamos Space Science Outreach (LASSO) Program

    NASA Astrophysics Data System (ADS)

    Barker, P. L.; Skoug, R. M.; Alexander, R. J.; Thomsen, M. F.; Gary, S. P.

    2002-12-01

    The Los Alamos Space Science Outreach (LASSO) program features summer workshops in which K-14 teachers spend several weeks at LANL learning space science from Los Alamos scientists and developing methods and materials for teaching this science to their students. The program is designed to provide hands-on space science training to teachers as well as assistance in developing lesson plans for use in their classrooms. The program supports an instructional model based on education research and cognitive theory. Students and teachers engage in activities that encourage critical thinking and a constructivist approach to learning. LASSO is run through the Los Alamos Science Education Team (SET). SET personnel have many years of experience in teaching, education research, and science education programs. Their involvement ensures that the teacher workshop program is grounded in sound pedagogical methods and meets current educational standards. Lesson plans focus on current LANL satellite projects to study the solar wind and the Earth's magnetosphere. LASSO is an umbrella program for space science education activities at Los Alamos National Laboratory (LANL) that was created to enhance the science and math interests and skills of students from New Mexico and the nation. The LASSO umbrella allows maximum leveraging of EPO funding from a number of projects (and thus maximum educational benefits to both students and teachers), while providing a format for the expression of the unique science perspective of each project.

  4. Optical velocimetry at the Los Alamos Proton Radiography Facility

    NASA Astrophysics Data System (ADS)

    Tupa, Dale; Tainter, Amy; Neukirch, Levi; Hollander, Brian; Buttler, William; Holtkamp, David; The Los Alamos Proton Radiography Team Team

    2016-05-01

    The Los Alamos Proton Radiography Facility (pRad) employs a high-energy proton beam to image the properties and behavior of materials driven by high explosives. We will discuss features of pRad and describe some recent experiments, highlighting optical diagnostics for surface velocity measurements.

  5. Working with Fermi at Chicago and Los Alamos

    NASA Astrophysics Data System (ADS)

    Garwin, Richard L.

    2010-02-01

    I discuss my experience with Enrico Fermi as student and fellow faculty member at Chicago and with him as consultants to the Los Alamos Scientific Laboratory in 1950-1952. The talk shares observations about this great physicist and exemplary human being. )

  6. Indeterminate and discrepant rapid HIV test results in couples' HIV testing and counselling centres in Africa

    PubMed Central

    2011-01-01

    Background Many HIV voluntary testing and counselling centres in Africa use rapid antibody tests, in parallel or in sequence, to establish same-day HIV status. The interpretation of indeterminate or discrepant results between different rapid tests on one sample poses a challenge. We investigated the use of an algorithm using three serial rapid HIV tests in cohabiting couples to resolve unclear serostatuses. Methods Heterosexual couples visited the Rwanda Zambia HIV Research Group testing centres in Kigali, Rwanda, and Lusaka, Zambia, to assess HIV infection status. Individuals with unclear HIV rapid antibody test results (indeterminate) or discrepant results were asked to return for repeat testing to resolve HIV status. If either partner of a couple tested positive or indeterminate with the screening test, both partners were tested with a confirmatory test. Individuals with indeterminate or discrepant results were further tested with a tie-breaker and monthly retesting. HIV-RNA viral load was determined when HIV status was not resolved by follow-up rapid testing. Individuals were classified based on two of three initial tests as "Positive", "Negative" or "Other". Follow-up testing and/or HIV-RNA viral load testing determined them as "Infected", "Uninfected" or "Unresolved". Results Of 45,820 individuals tested as couples, 2.3% (4.1% of couples) had at least one discrepant or indeterminate rapid result. A total of 65% of those individuals had follow-up testing and of those individuals initially classified as "Negative" by three initial rapid tests, less than 1% were resolved as "Infected". In contrast, of those individuals with at least one discrepant or indeterminate result who were initially classified as "Positive", only 46% were resolved as "Infected", while the remainder was resolved as "Uninfected" (46%) or "Unresolved" (8%). A positive HIV serostatus of one of the partners was a strong predictor of infection in the other partner as 48% of individuals who

  7. Environmental Survey preliminary report, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    Not Available

    1988-01-01

    This report presents the preliminary findings from the first phase of the Environmental Survey of the United States Department of Energy's (DOE) Los Alamos National Laboratory (LANL), conducted March 29, 1987 through April 17, 1987. The Survey is being conducted by an interdisciplinary team of environmental specialists, led and managed by the Office of Environment, Safety and Health's Office of Environmental Audit. Individual team components are outside experts being supplied by a private contractor. The objective of the Survey is to identify environmental problems and areas of environmental risk associated with the LANL. The Survey covers all environmental media and all areas of environmental regulation. It is being performed in accordance with the DOE Environmental Survey Manual. The on-site phase of the Survey involves the review of existing site environmental data, observations of the operations carried on at the LANL, and interviews with site personnel. The Survey team developed Sampling and Analysis Plan to assist in further assessing certain of the environmental problems identified during its on-site activities. The Sampling and Analysis Plan will be executed by the Idaho National Engineering Laboratory. When completed, the results will be incorporated into the LANL Environmental Survey Interim Report. The Interim Report will reflect the final determinations of the Survey for the LANL. 65 refs., 68 figs., 73 tabs.

  8. Environmental assessment for effluent reduction, Los Alamos National Laboratory, Los Alamos, New Mexico

    SciTech Connect

    1996-09-11

    The Department of Energy (DOE) proposes to eliminate industrial effluent from 27 outfalls at Los Alamos National Laboratory (LANL). The Proposed Action includes both simple and extensive plumbing modifications, which would result in the elimination of industrial effluent being released to the environment through 27 outfalls. The industrial effluent currently going to about half of the 27 outfalls under consideration would be rerouted to LANL`s sanitary sewer system. Industrial effluent from other outfalls would be eliminated by replacing once-through cooling water systems with recirculation systems, or, in a few instances, operational changes would result in no generation of industrial effluent. After the industrial effluents have been discontinued, the affected outfalls would be removed from the NPDES Permit. The pipes from the source building or structure to the discharge point for the outfalls may be plugged, or excavated and removed. Other outfalls would remain intact and would continue to discharge stormwater. The No Action alternative, which would maintain the status quo for LANL`s outfalls, was also analyzed. An alternative in which industrial effluent would be treated at the source facilities was considered but dismissed from further analysis because it would not reasonably meet the DOE`s purpose for action, and its potential environmental effects were bounded by the analysis of the Proposed Action and the No Action alternatives.

  9. Commercialization of Los Alamos National Laboratory technologies via small businesses. Final report

    SciTech Connect

    Brice, R.; Carton, D.; Rhyne, T.

    1997-06-01

    Appendices are presented from a study performed on a concept model system for the commercialization of Los Alamos National Laboratory technologies via small businesses. Topics include a summary of information from the joint MCC/Los Alamos technology conference; a comparison of New Mexico infrastructure to other areas; a typical licensing agreement; technology screening guides; summaries of specific DOE/UC/Los Alamos documents; a bibliography; the Oak Ridge National Laboratory TCRD; The Ames Center for Advanced Technology Development; Los Alamos licensing procedures; presentation of slides from monthly MCC/Los Alamos review meetings; generalized entrepreneurship model; and a discussion on receiving equity for technology.

  10. Phylogenetic Relatedness of Circulating HIV-1C Variants in Mochudi, Botswana

    PubMed Central

    Novitsky, Vladimir; Bussmann, Hermann; Logan, Andrew; Moyo, Sikhulile; van Widenfelt, Erik; Okui, Lillian; Mmalane, Mompati; Baca, Jeannie; Buck, Lauren; Phillips, Eleanor; Tim, David; McLane, Mary Fran; Lei, Quanhong; Wang, Rui; Makhema, Joseph; Lockman, Shahin; DeGruttola, Victor; Essex, M.

    2013-01-01

    Background Determining patterns of HIV transmission is increasingly important for the most efficient use of modern prevention interventions. HIV phylogeny can provide a better understanding of the mechanisms underlying HIV transmission networks in communities. Methods To reconstruct the structure and dynamics of a local HIV/AIDS epidemic, the phylogenetic relatedness of HIV-1 subtype C env sequences obtained from 785 HIV-infected community residents in the northeastern sector of Mochudi, Botswana, during 2010–2013 was estimated. The genotyping coverage was estimated at 44%. Clusters were defined based on relatedness of HIV-1C env sequences and bootstrap support of splits. Results The overall proportion of clustered HIV-1C env sequences was 19.1% (95% CI 17.5% to 20.8%). The proportion of clustered sequences from Mochudi was significantly higher than the proportion of non-Mochudi sequences that clustered, 27.0% vs. 14.7% (p = 5.8E-12; Fisher exact test). The majority of clustered Mochudi sequences (90.1%; 95% CI 85.1% to 93.6%) were found in the Mochudi-unique clusters. None of the sequences from Mochudi clustered with any of the 1,244 non-Botswana HIV-1C sequences. At least 83 distinct HIV-1C variants, or chains of HIV transmission, in Mochudi were enumerated, and their sequence signatures were reconstructed. Seven of 20 genotyped seroconverters were found in 7 distinct clusters. Conclusions The study provides essential characteristics of the HIV transmission network in a community in Botswana, suggests the importance of high sampling coverage, and highlights the need for broad HIV genotyping to determine the spread of community-unique and community-mixed viral variants circulating in local epidemics. The proposed methodology of cluster analysis enumerates circulating HIV variants and can work well for surveillance of HIV transmission networks. HIV genotyping at the community level can help to optimize and balance HIV prevention strategies in trials and

  11. Probabilistic risk assessment for the Los Alamos Meson Physics Facility worst-case design-basis accident

    SciTech Connect

    Sharirli, M.; Butner, J.M.; Rand, J.L.; Macek, R.J. ); McKinney, S.J. ); Roush, M.L. . Center for Reliability Engineering)

    1992-01-01

    This paper presents results from a Los Alamos National Laboratory Engineering and Safety Analysis Group assessment of the worse-case design-basis accident associated with the Clinton P. Anderson Meson Physics Facility (LAMPF)/Weapons Neutron Research (WNR) Facility. The primary goal of the analysis was to quantify the accident sequences that result in personnel radiation exposure in the WNR Experimental Hall following the worst-case design-basis accident, a complete spill of the LAMPF accelerator 1L beam. This study also provides information regarding the roles of hardware systems and operators in these sequences, and insights regarding the areas where improvements can increase facility-operation safety. Results also include confidence ranges to incorporate combined effects of uncertainties in probability estimates and importance measures to determine how variations in individual events affect the frequencies in accident sequences.

  12. Probabilistic risk assessment for the Los Alamos Meson Physics Facility worst-case design-basis accident

    SciTech Connect

    Sharirli, M.; Butner, J.M.; Rand, J.L.; Macek, R.J.; McKinney, S.J.; Roush, M.L.

    1992-12-01

    This paper presents results from a Los Alamos National Laboratory Engineering and Safety Analysis Group assessment of the worse-case design-basis accident associated with the Clinton P. Anderson Meson Physics Facility (LAMPF)/Weapons Neutron Research (WNR) Facility. The primary goal of the analysis was to quantify the accident sequences that result in personnel radiation exposure in the WNR Experimental Hall following the worst-case design-basis accident, a complete spill of the LAMPF accelerator 1L beam. This study also provides information regarding the roles of hardware systems and operators in these sequences, and insights regarding the areas where improvements can increase facility-operation safety. Results also include confidence ranges to incorporate combined effects of uncertainties in probability estimates and importance measures to determine how variations in individual events affect the frequencies in accident sequences.

  13. Using HIV Networks to Inform Real Time Prevention Interventions

    PubMed Central

    Little, Susan J.; Kosakovsky Pond, Sergei L.; Anderson, Christy M.; Young, Jason A.; Wertheim, Joel O.; Mehta, Sanjay R.; May, Susanne; Smith, Davey M.

    2014-01-01

    Objective To reconstruct the local HIV-1 transmission network from 1996 to 2011 and use network data to evaluate and guide efforts to interrupt transmission. Design HIV-1 pol sequence data were analyzed to infer the local transmission network. Methods We analyzed HIV-1 pol sequence data to infer a partial local transmission network among 478 recently HIV-1 infected persons and 170 of their sexual and social contacts in San Diego, California. A transmission network score (TNS) was developed to estimate the risk of HIV transmission from a newly diagnosed individual to a new partner and target prevention interventions. Results HIV-1 pol sequences from 339 individuals (52.3%) were highly similar to sequences from at least one other participant (i.e., clustered). A high TNS (top 25%) was significantly correlated with baseline risk behaviors (number of unique sexual partners and insertive unprotected anal intercourse (p = 0.014 and p = 0.0455, respectively) and predicted risk of transmission (p<0.0001). Retrospective analysis of antiretroviral therapy (ART) use, and simulations of ART targeted to individuals with the highest TNS, showed significantly reduced network level HIV transmission (p<0.05). Conclusions Sequence data from an HIV-1 screening program focused on recently infected persons and their social and sexual contacts enabled the characterization of a highly connected transmission network. The network-based risk score (TNS) was highly correlated with transmission risk behaviors and outcomes, and can be used identify and target effective prevention interventions, like ART, to those at a greater risk for HIV-1 transmission. PMID:24901437

  14. An HIV-1 transmission case possibly associated with manicure care.

    PubMed

    Matsuda, Elaine Monteiro; Coelho, Luana Portes Ozório; Pimentel, Victor Figueiredo; Onias, Humberto Barjud; Brigido, Luís Fernando de Macedo

    2014-11-01

    A recently diagnosed 22-year-old female with no history of transmission risk factors prompted a thorough investigation of possible alternative risk factors. As the patient had evidence of advanced disease and laboratory data compatible with long-standing infection, past events were reviewed. About 10 years ago the patient shared manicure utensils with an older cousin, later known to be HIV infected; this prompted the phylogenetic analysis of the HIV sequences of both patients. Phylogenetic analyses of partial HIV-1 polymerase and envelope sequences from both patients revealed highly related sequences, with an estimated common ancestor date (about 11 years ago) that coincided with the putative sharing of manicure instruments, during a time in which the cousin was not virally suppressed. Taken together, the information about the infection of this patient suggests the use of shared manicure instruments as an alternative route of fomite HIV-1 transmission.

  15. Transition to Parenthood and HIV Infection in Rural Zimbabwe

    PubMed Central

    Piccarreta, Raffaella; Gregson, Simon; Melegaro, Alessia

    2016-01-01

    Background The relationship between the risk of acquiring human immunodeficiency virus (HIV) infection and people’s choices about life course events describing the transition to parenthood–sexual debut, union (in the form of marriage, cohabitation, or long-term relationship), and parenthood–is still unclear. A crucial role in shaping this relationship may be played by the sequence of these events and by their timing. This suggests the opportunity to focus on the life courses in their entirety rather than on the specific events, thus adopting a holistic approach that regards each individual’s life course trajectory as a whole. Methods We summarise the individual life courses describing the transition to parenthood using ordered sequences of the three considered events. We aim to (i) investigate the association between the sequences and HIV infection, and (ii) understand how these sequences interact with known mechanisms for HIV transmission, such as the length of sexual exposure and the experience of non-regular sexual partnerships. For this purpose, we use data from a general population cohort study run in Manicaland (Zimbabwe), a Sub-Saharan African area characterised by high HIV prevalence. Results For both genders, individuals who experienced either premarital or delayed childbearing have higher HIV risk compared to individuals following more standard transitions. This can be explained by the interplay of the sequences with known HIV proximate determinants, e.g., a longer exposure to sexual activity and higher rates of premarital sex. Moreover, we found that people in the younger birth cohorts experience more normative and safer sequences. Conclusions The shift of younger generations towards more normative transitions to parenthood is a sign of behaviour change that might have contributed to the observed reduction in HIV prevalence in the area. On the other hand, for people with less normative transitions, targeted strategies are essential for HIV

  16. Cyclophilin B enhances HIV-1 infection.

    PubMed

    DeBoer, Jason; Madson, Christian J; Belshan, Michael

    2016-02-01

    Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import. PMID:26774171

  17. The engineering institute of Los Alamos National Laboratory

    SciTech Connect

    Farrar, Charles R; Park, Gyuhae; Cornwell, Phillip J; Todd, Michael D

    2008-01-01

    Los Alamos National Laboratory (LANL) and the University of California, San Diego (UCSD) have taken the unprecedented step of creating a collaborative, multi-disciplinary graduate education program and associated research agenda called the Engineering Institute. The mission of the Engineering Institute is to develop a comprehensive approach for conducting LANL mission-driven, multidisciplinary engineering research and to improve recruiting, revitalization, and retention of the current and future staff necessary to support the LANL' s national security responsibilities. The components of the Engineering Institute are (1) a joint LANL/UCSD degree program, (2) joint LANL/UCSD research projects, (3) the Los Alamos Dynamic Summer School, (4) an annual workshop, and (5) industry short courses. This program is a possible model for future industry/government interactions with university partners.

  18. Tiger Team Assessment of the Los Alamos National Laboratory

    SciTech Connect

    Not Available

    1991-11-01

    This report documents the Tiger Team Assessment of the Los Alamos National Laboratory (LANL) located in Los Alamos, New Mexico. LANL is operated for the US Department of Energy (DOE) by the University of California. The Tiger Team Assessment was conducted from September 23 to November 8, 1991, under the auspices of the DOE Office of Special Projects, Office of Assistant Secretary for Environment, Safety and Health. The assessment was comprehensive, encompassing environmental, safety, and health (ES H) disciplines; management; and contractor and DOE self-assessments. Compliance with applicable Federal, state, and local regulations; applicable DOE Orders; best management practices; and internal LANL site requirements was assessed. In addition, an evaluation of the adequacy and effectiveness of the DOE and the site contractors' management of ES H/quality assurance programs was conducted. This volume discusses findings concerning the environmental assessment.

  19. Airport-Noise Levels and Annoyance Model (ALAMO) user's guide

    NASA Technical Reports Server (NTRS)

    Deloach, R.; Donaldson, J. L.; Johnson, M. J.

    1986-01-01

    A guide for the use of the Airport-Noise Level and Annoyance MOdel (ALAMO) at the Langley Research Center computer complex is provided. This document is divided into 5 primary sections, the introduction, the purpose of the model, and an in-depth description of the following subsystems: baseline, noise reduction simulation and track analysis. For each subsystem, the user is provided with a description of architecture, an explanation of subsystem use, sample results, and a case runner's check list. It is assumed that the user is familiar with the operations at the Langley Research Center (LaRC) computer complex, the Network Operating System (NOS 1.4) and CYBER Control Language. Incorporated within the ALAMO model is a census database system called SITE II.

  20. Penetrating radiation: applications at Los Alamos National Laboratory

    NASA Astrophysics Data System (ADS)

    Watson, Scott; Hunter, James; Morris, Christopher

    2013-09-01

    Los Alamos has used penetrating radiography extensively throughout its history dating back to the Manhattan Project where imaging dense, imploding objects was the subject of intense interest. This interest continues today as major facilities like DARHT1 have become the mainstay of the US Stockpile Stewardship Program2 and the cornerstone of nuclear weapons certification. Meanwhile, emerging threats to national security from cargo containers and improvised explosive devices (IEDs) have invigorated inspection efforts using muon tomography, and compact x-ray radiography. Additionally, unusual environmental threats, like those from underwater oil spills and nuclear power plant accidents, have caused renewed interest in fielding radiography in severe operating conditions. We review the history of penetrating radiography at Los Alamos and survey technologies as presently applied to these important problems.

  1. HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

    PubMed

    Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

    2011-01-01

    Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy.

  2. Rare HIV-1 Subtype J Genomes and a New H/U/CRF02_AG Recombinant Genome Suggests an Ancient Origin of HIV-1 in Angola.

    PubMed

    Bártolo, Inês; Calado, Rita; Borrego, Pedro; Leitner, Thomas; Taveira, Nuno

    2016-08-01

    Angola has an extremely diverse HIV-1 epidemic fueled in part by the frequent interchange of people with the Democratic Republic of Congo (DRC) and Republic of Congo (RC). Characterization of HIV-1 strains circulating in Angola should help to better understand the origin of HIV-1 subtypes and recombinant forms and their transmission dynamics. In this study we characterize the first near full-length HIV-1 genomic sequences from HIV-1 infected individuals from Angola. Samples were obtained in 1993 from three HIV-1 infected patients living in Cabinda, Angola. Near full-length genomic sequences were obtained from virus isolates. Maximum likelihood phylogenetic tree inference and analyses of potential recombination patterns were performed to evaluate the sequence classifications and origins. Phylogenetic and recombination analyses revealed that one virus was a pure subtype J, another mostly subtype J with a small uncertain region, and the final virus was classified as a H/U/CRF02_AG recombinant. Consistent with their epidemiological data, the subtype J sequences were more closely related to each other than to other J sequences previously published. Based on the env gene, taxa from Angola occur throughout the global subtype J phylogeny. HIV-1 subtypes J and H are present in Angola at low levels since at least 1993. Low transmission efficiency and/or high recombination potential may explain their limited epidemic success in Angola and worldwide. The high diversity of rare subtypes in Angola suggests that Angola was part of the early establishment of the HIV-1 pandemic.

  3. Using the Internet in Middle Schools: A Model for Success. A Collaborative Effort between Los Alamos National Laboratory (LANL) and Los Alamos Middle School (LAMS).

    ERIC Educational Resources Information Center

    Addessio, Barbara K.; And Others

    Los Alamos National Laboratory (LANL) developed a model for school networking using Los Alamos Middle School as a testbed. The project was a collaborative effort between the school and the laboratory. The school secured administrative funding for hardware and software; and LANL provided the network architecture, installation, consulting, and…

  4. National survey of prevalent HIV strains: limited genetic variation of Korean HIV-1 clade B within the population of Korean men who have sex with men.

    PubMed

    Kim, Gab Jung; Nam, Jeong-Gu; Shin, Bo Gyeong; Kee, Mee Kyeong; Kim, Eun-Jin; Lee, Joo-Shil; Kim, Sung Soon

    2008-06-01

    The evolution of HIV is the result of an explosive combination of factors-a high rate of mutation, replication dynamics, frequent recombination, and natural selection. To understand the evolution of the distinctive Korean HIV-1 B clade, we investigated the characteristics of the genetic variation of the HIV-1 subtype B env gene within the group of Korean men who have sex with men (MSM). From 1985 to 2005, 700 HIV-1-infected Koreans were sequenced at the V1 to V5 region of the HIV-1 env gene. In the phylogenetic analysis, 560 isolates were identified as HIV-1 subtype B, and 489 of the 560 isolates were HIV-1 Korean clade B. Based on epidemiologic investigation, 249 of 700 HIV-1-infected patients were HIV-1 subtype B-infected MSM. Interestingly, the proportion of the GPGS motif in MSM infected by Koreans was 1.6 times higher than in MSM infected by foreigners, and the genetic expansions of diversity and divergence for HIV-1 subtype B in Korean MSM were 2.1% and 2.5%, respectively. This was much lower than those observed in other countries. Therefore, our findings imply that the HIV strains in this group were closely related. This result may be helpful for understanding the evolution of the distinct HIV-1 Korean B clade.

  5. Automated medical information system of the Los Alamos Scientific Laboratory

    SciTech Connect

    Eagan, G.D.; Grier, R.S.

    1980-01-01

    The Medical Information System (MIS) at the Los Alamos Scientific Laboratory automates the acquisition, storage, and retrieval of medical information concerning the nine thousand project-connected personnel. The MIS incorporates an on-line, interactive medical history questionnaire, mark sense form processing, and automated coronary risk assesment in the medical evaluation process. Also, MIS has created the ability for long-term study and comparison of employee health as well as made the physician's time more effective.

  6. Los Alamos Canyon Ice Rink Parking Flood Plain Assessment

    SciTech Connect

    Hathcock, Charles Dean

    2015-02-10

    The project location is in Los Alamos Canyon east of the ice rink facility at the intersection of West and Omega roads (Figure 1). Forty eight parking spaces will be constructed on the north and south side of Omega Road, and a lighted walking path will be constructed to the ice rink. Some trees will be removed during this action. A guardrail of approximately 400 feet will be constructed along the north side of West Road to prevent unsafe parking in that area.

  7. Evolution of some Los Alamos flux compression programs

    SciTech Connect

    Fowler, C.M.; Goforth, J.H.

    1996-12-31

    When we were approached to give a general discussion of some aspects of the Los Alamos flux compression program, we decided to present historical backgrounds of a few topics that have some relevance to programs that we very much In the forefront of activities going on today. Of some thirty abstracts collected at Los Alamos for this conference, ten of them dealt with electromagnetic acceleration of materials, notably the compression of heavy liners, and five dealt with plasma compression. Both of these topics have been under investigation, off and on, from the time a formal flux compression program was organized at Los Alamos. We decided that a short overview of work done In these areas would be of some interest. Some of the work described below has been discussed in Laboratory reports that, while referenced and available, are not readily accessible. For completeness, some previously published, accessible work Is also discussed but much more briefly. Perhaps the most striking thing about the early work In these two areas is how primitive much of it was when compared to the far more sophisticated, related activities of today. Another feature of these programs, actually for most programs, Is their cyclic nature. Their relevance and/or funding seems to come land go. Eventually, many of the older programs come back into favor. Activities Involving the dense plasma focus (DPF), about which some discussions will be given later, furnish a classic example of this kind, coming Into and then out of periods of heightened interest. We devote the next two sections of this paper to a review of our work In magnetic acceleration of solids and of plasma compression. A final section gives a survey of our work In which thin foils are imploded to produce intense quantities of son x-rays. The authors are well aware of much excellent work done elsewhere In all of these topics, but partly because of space limitations, have confined this discussion to work done at Los Alamos.

  8. Smoking and HIV

    MedlinePlus

    ... 28, 2014 Select a Language: Fact Sheet 803 Smoking and HIV WHY IS SMOKING MORE DANGEROUS FOR ... It can also worsen liver problems like hepatitis. Smoking and Side Effects People with HIV who smoke ...

  9. HIV and Pregnancy

    MedlinePlus

    ... Pregnancy Patient Education FAQs HIV and Pregnancy Patient Education Pamphlets - Spanish HIV and Pregnancy FAQ113, December 2012 PDF Format ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  10. HIV and AIDS

    MedlinePlus

    ... that causes the disease AIDS. HIV Hurts the Immune System People who are HIV positive have been tested ... to everyone in the world. When the person's immune system has weakened and more of the blood's T ...

  11. Older People and HIV

    MedlinePlus

    ... Many older people believe that HIV only affects younger people Most older people get little training in ... diseases among older people, as they do for younger people. Physicians may not diagnose HIV infection in ...

  12. Testing for HIV

    MedlinePlus

    ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability (Biologics) HIV Home Test Kits Testing for HIV Share Tweet Linkedin Pin it More ...

  13. HIV and Cardiovascular Disease

    MedlinePlus

    ... CVD. ART can increase blood fats (cholesterol and triglycerides, see fact sheet 123.) It can also help ... disease. HIV infection decreases good cholesterol and increases triglycerides. HIV causes inflammation. This can also contribute to ...

  14. Reduce HIV Risk

    MedlinePlus

    ... Control and Prevention (CDC) has used them as models, and Dr. Jemmott was invited to South Africa to help decrease HIV/AIDS there. "For the past 15 years, I have observed how the HIV/AIDS epidemic ...

  15. Overview of laser technology at Los Alamos National Laboratory

    SciTech Connect

    Lewis, G.K.; Cremers, D.A.

    1994-09-01

    Los Alamos National Laboratory has had a long history of involvement in laser sciences and has been recognized both for its large laser programs and smaller scale developments in laser technology and applications. The first significant program was with the Rover nuclear-based rocket propulsion system in 1968 to study laser initiated fusion. From here applications spread to programs in laser isotope separation and development of large lasers for fusion. These programs established the technological human resource base of highly trained laser physicists, engineers, and chemists that remain at the Laboratory today. Almost every technical division at Los Alamos now has some laser capability ranging from laser development, applications, studies on nonlinear processes, modeling and materials processing. During the past six years over eight R&D-100 Awards have been received by Los Alamos for development of laser-based techniques and instrumentation. Outstanding examples of technology developed include LIDAR applications to environmental monitoring, single molecule detection using fluorescence spectroscopy, a laser-based high kinetic energy source of oxygen atoms produced by a laser-sustained plasma, laser-induced breakdown spectroscopy (LIBS) for compositional, analysis, thin film high temperature superconductor deposition, multi-station laser welding, and direct metal deposition and build-up of components by fusing powder particles with a laser beam.

  16. Los Alamos, Toshiba probing Fukushima with cosmic rays

    ScienceCinema

    Morris, Christopher

    2016-07-12

    Los Alamos National Laboratory has announced an impending partnership with Toshiba Corporation to use a Los Alamos technique called muon tomography to safely peer inside the cores of the Fukushima Daiichi reactors and create high-resolution images of the damaged nuclear material inside without ever breaching the cores themselves. The initiative could reduce the time required to clean up the disabled complex by at least a decade and greatly reduce radiation exposure to personnel working at the plant. Muon radiography (also called cosmic-ray radiography) uses secondary particles generated when cosmic rays collide with upper regions of Earth's atmosphere to create images of the objects that the particles, called muons, penetrate. The process is analogous to an X-ray image, except muons are produced naturally and do not damage the materials they contact. Muon radiography has been used before in imaginative applications such as mapping the interior of the Great Pyramid at Giza, but Los Alamos's muon tomography technique represents a vast improvement over earlier technology.

  17. Los Alamos, Toshiba probing Fukushima with cosmic rays

    SciTech Connect

    Morris, Christopher

    2014-06-16

    Los Alamos National Laboratory has announced an impending partnership with Toshiba Corporation to use a Los Alamos technique called muon tomography to safely peer inside the cores of the Fukushima Daiichi reactors and create high-resolution images of the damaged nuclear material inside without ever breaching the cores themselves. The initiative could reduce the time required to clean up the disabled complex by at least a decade and greatly reduce radiation exposure to personnel working at the plant. Muon radiography (also called cosmic-ray radiography) uses secondary particles generated when cosmic rays collide with upper regions of Earth's atmosphere to create images of the objects that the particles, called muons, penetrate. The process is analogous to an X-ray image, except muons are produced naturally and do not damage the materials they contact. Muon radiography has been used before in imaginative applications such as mapping the interior of the Great Pyramid at Giza, but Los Alamos's muon tomography technique represents a vast improvement over earlier technology.

  18. James L. Tuck Los Alamos ball lightning pioneer

    SciTech Connect

    Baker, D.A.

    1999-07-01

    James Tuck was well known for starting the Project Sherwood group at Los Alamos Scientific Laboratory in 1952. This group was formed to study and develop concepts for controlled fusion energy. In his later years after retiring from Controlled Fusion Division, he continued research at Los Alamos on the topic of ball lightning. He traveled widely giving lectures on both observations of others and his own experimental efforts. He collected anecdotal observations obtained from those in his lecture audiences during his travels and from responses from newspaper articles where he asked for specific information from ball lightning observers. He finally cut off this collection of data when the number of responses became overwhelming. The author's primary publication on ball lightning was a short laboratory report. He planned on publishing a book on the subject but this was never completed before his death. Tuck focused his experimental effort on attempting to duplicate the production of plasma balls claimed to be observed in US Navy submarines when a switch was opened under overload conditions with battery power. During lunch breaks he made use of a Los Alamos N-division battery bank facility to mock up a submarine power pack and switch gear. This non-funded effort was abruptly terminated when an explosion occurred in the facility. An overview of Tuck's research and views will be given. The flavor Jim's personality as well as a ball produced with his experimental apparatus will be shown using video chips.

  19. Discrepant amplification results during the development of an assay leads to reclassification of two AIDS reagent repository HIV-2 isolates as HIV-1.

    PubMed

    Jagodzinski, Linda L; Liu, Ying; Hack, Holly R; Kibirige, Catherine; Peel, Sheila A; Manak, Mark M

    2014-01-01

    The development and verification of HIV-2 assays depends in part on the availability of well-characterized samples, including those from reagent repositories. During the development of an HIV-2 RNA quantification assay, two HIV-2 viral isolates (CDC 301340 and CDC 301342) obtained from the NIAID AIDS Reagent and Reference Repository were not detected leading to an investigation. Two HIV-2 primers/probe sets of known performance in real-time viral RNA quantification assays, targeting different regions of the virus, also failed to generate RT-PCR products for these two isolates. These isolates were tested in the HIV-1 specific COBAS AmpliPrep/COBAS TaqMan HIV-1 Test v2.0 (Roche Molecular Diagnostics) and were quantified at high copy number. Other HIV-2 isolates tested were not amplified in the COBAS HIV-1 TaqMan assay. Furthermore, the discrepant isolates were highly reactive in an HIV-1 p24 antigen test while the other HIV-2 isolates showed very weak, if any, cross-reactivity with the HIV-1 p24 assay. Phylogenetic tree analysis of sequences from the protease-reverse transcriptase regions of the discrepant HIV-2 isolates mapped with HIV-1 Group M, Subtype CRF02_AG confirming these isolates were of HIV-1 origin and had been misclassified as HIV-2. The use of misclassified isolates in the verification of molecular and immunological assays can lead to misinterpretation of test results, misdirection of efforts into assay redesign and increased development costs. The results of this study were shared with the NIAID AIDS Reagent Program, leading to the reclassification of the two discrepant isolates as HIV-1.

  20. HIV and the menopause.

    PubMed

    Fan, Maria D; Maslow, Bat-Sheva; Santoro, Nanette; Schoenbaum, Ellie

    2008-12-01

    Dramatic improvement in the survival of the HIV population has occurred with the ascendance of highly active antiretroviral therapy (HAART). In the foreseeable future, HIV-infected women who acquired disease during the peak years of the epidemic are expected to survive to experience menopause and even years beyond. The HIV epidemic may be viewed as 'mature', as its earlier victims become part of the geriatric population. Research about the process of menopause in HIV-infected women and, conversely, about HIV infection in women undergoing menopause is currently limited. Existing research suggests that the process of menopause is affected by HIV infection, inasmuch as infected women appear to experience menopause at an earlier age, with greater symptomatology, and with different reproductive hormone profiles compared with HIV-uninfected women. HIV infection also appears to affect bone mineral density, cardiovascular disease and cognition, with some age-related interactions. Lifestyle and demographic factors have pervasive importance for both HIV infection and the menopause in women. This article reviews the current state of knowledge about the menopausal process in HIV-infected women, and the common conditions in postmenopausal women that are likely to be affected by HIV infection. Clinicians should appreciate the potential role of HIV infection in caring for menopause-aged women. PMID:19037065

  1. HIV Disease: Current Concepts.

    ERIC Educational Resources Information Center

    Keeling, Richard P.

    1993-01-01

    Describes human immunodeficiency virus (HIV), newly characterized human retrovirus which causes chronic, progressive, immune deficiency disease, the most severe phase of which is Acquired Immune Deficiency Syndrome (AIDS). Reviews most important current epidemiologic, clinical, and virologic information about HIV and HIV disease and provides…

  2. Novel anti-HIV peptides containing multiple copies of artificially designed heptad repeat motifs

    SciTech Connect

    Shi Weiguo; Qi Zhi; Pan Chungen; Xue Na; Debnath, Asim K.; Qie Jiankun; Jiang Shibo Liu Keliang

    2008-10-03

    The peptidic anti-HIV drug T20 (Fuzeon) and its analog C34 share a common heptad repeat (HR) sequence, but they have different functional domains, i.e., pocket- and lipid-binding domains (PBD and LBD, respectively). We hypothesize that novel anti-HIV peptides may be designed by using artificial sequences containing multiple copies of HR motifs plus zero, one or two functional domains. Surprisingly, we found that the peptides containing only the non-natural HR sequences could significantly inhibit HIV-1 infection, while addition of PBD and/or LBD to the peptides resulted in significant improvement of anti-HIV-1 activity. These results suggest that these artificial HR sequences, which may serve as structural domains, could be used as templates for the design of novel antiviral peptides against HIV and other viruses with class I fusion proteins.

  3. Streamlining HIV Testing for HIV Preexposure Prophylaxis

    PubMed Central

    Leigler, Teri; Kallas, Esper; Schechter, Mauro; Sharma, Usha; Glidden, David; Grant, Robert M.

    2014-01-01

    HIV-testing algorithms for preexposure prophylaxis (PrEP) should be optimized to minimize the risk of drug resistance, the time off PrEP required to evaluate false-positive screening results, and costs and to expedite the start of therapy for those confirmed to be infected. HIV rapid tests (RTs) for anti-HIV antibodies provide results in less than 1 h and can be conducted by nonlicensed staff at the point of care. In many regions, Western blot (WB) testing is required to confirm reactive RT results. WB testing, however, causes delays in diagnosis and adds expense. The iPrEx study evaluated the safety and efficacy of daily oral emtricitabine-tenofovir disoproxil fumarate among HIV-seronegative men and transgender women who have sex with men: HIV infection was assessed with two RTs plus WB confirmation, followed by HIV-1 plasma viral load testing. During the iPrEx study, there were 51,260 HIV status evaluations among 2,499 volunteers using RTs: 142 (0.28%) had concordant positive results (100% were eventually confirmed) and 19 (0.04%) had discordant results among 14 participants; 11 were eventually determined to be HIV infected. A streamlined approach using only one RT to screen and a second RT to confirm (without WB) would have had nearly the same accuracy. Discrepant RT results are best evaluated with nucleic acid testing, which would also increase sensitivity. PMID:25378570

  4. Neuropsychological abnormalities in AIDS and asymptomatic HIV seropositive patients.

    PubMed Central

    Villa, G; Monteleone, D; Marra, C; Bartoli, A; Antinori, A; Pallavicini, F; Tamburrini, E; Izzi, I

    1993-01-01

    Neuropsychological and immunological parameters were studied in 36 AIDS patients with early disease and without clinical, laboratory, and neuroradiological signs of CNS impairment, and also in 33 asymptomatic HIV seropositive subjects. Many AIDS patients performed abnormally on timed psychomotor tasks, tasks involving sequencing and "set-shifting", and memory tasks stressing attention, learning, active retrieval, and monitoring of information. Asymptomatic HIV seropositive subjects as a group did not perform significantly worse than controls. However, on the basis of a cut off number of pathological performances on neuropsychological tasks, 52.8% of AIDS and 30.3% of asymptomatic HIV seropositive subjects had cognitive impairment, compared with 3.9% of HIV seronegative controls. Low values of CD4+ cells and of CD4+/CD8+ ratio and high titres of P-24 antigen in the blood prevailed among subjects with cognitive impairment, especially in the asymptomatic HIV seropositive group. PMID:8350104

  5. Ongoing HIV replication in cerebrospinal fluid under successful monotherapy.

    PubMed

    Bierhoff, Marieke; Boucher, Charles A B; Fibriani, Azzania; Ten Kate, Reinier W

    2013-01-01

    We report a case of an HIV-infected patient who was successfully treated with ritonavir/lopinavir (r/LPV) monotherapy for several years. He presented with neurological symptoms and high HIV RNA levels in cerebrospinal fluid (CSF). Sequencing of the HIV from the CSF revealed mutations in the protease gene reflecting resistance against most protease inhibitors, that is, lopinavir and ritonavir. His regimen was switched and after 2 months the HIV RNA viral load was again undetectable in both plasma as well as in CSF. Monotherapy with r/LPV may not be sufficient to fully suppress viral replication in the central nervous system in all individuals and may lead to compartimentalization and the selection of resistant mutations of HIV in the central nervous system. PMID:23344463

  6. Enrichment of intersubtype HIV-1 recombinants in a dual infection system using HIV-1 strain-specific siRNAs

    PubMed Central

    2011-01-01

    Background Intersubtype HIV-1 recombinants in the form of unique or stable circulating recombinants forms (CRFs) are responsible for over 20% of infections in the worldwide epidemic. Mechanisms controlling the generation, selection, and transmission of these intersubtype HIV-1 recombinants still require further investigation. All intersubtype HIV-1 recombinants are generated and evolve from initial dual infections, but are difficult to identify in the human population. In vitro studies provide the most practical system to study mechanisms, but the recombination rates are usually very low in dual infections with primary HIV-1 isolates. This study describes the use of HIV-1 isolate-specific siRNAs to enrich intersubtype HIV-1 recombinants and inhibit the parental HIV-1 isolates from a dual infection. Results Following a dual infection with subtype A and D primary HIV-1 isolates and two rounds of siRNA treatment, nearly 100% of replicative virus was resistant to a siRNA specific for an upstream target sequence in the subtype A envelope (env) gene as well as a siRNA specific for a downstream target sequence in the subtype D env gene. Only 20% (10/50) of the replicating virus had nucleotide substitutions in the siRNA-target sequence whereas the remaining 78% (39/50) harbored a recombination breakpoint that removed both siRNA target sequences, and rendered the intersubtype D/A recombinant virus resistant to the dual siRNA treatment. Since siRNAs target the newly transcribed HIV-1 mRNA, the siRNAs only enrich intersubtype env recombinants and do not influence the recombination process during reverse transcription. Using this system, a strong bias is selected for recombination breakpoints in the C2 region, whereas other HIV-1 env regions, most notably the hypervariable regions, were nearly devoid of intersubtype recombination breakpoints. Sequence conservation plays an important role in selecting for recombination breakpoints, but the lack of breakpoints in many conserved

  7. HIV and maternal mortality.

    PubMed

    Lathrop, Eva; Jamieson, Denise J; Danel, Isabella

    2014-11-01

    The majority of the 17 million women globally that are estimated to be infected with HIV live in Sub-Saharan Africa. Worldwide, HIV-related causes contributed to 19 000-56 000 maternal deaths in 2011 (6%-20% of maternal deaths). HIV-infected pregnant women have two to 10 times the risk of dying during pregnancy and the postpartum period compared with uninfected pregnant women. Many of these deaths can be prevented with the implementation of high-quality obstetric care, prevention and treatment of common co-infections, and treatment of HIV with ART. The paper summarizes what is known about HIV disease progression in pregnancy, specific causes of HIV-related maternal deaths, and the potential impact of treatment with antiretroviral therapy on maternal mortality. Recommendations are proposed for improving maternal health and decreasing maternal mortality among HIV-infected women based on existing evidence.

  8. Basic HIV/AIDS Statistics

    MedlinePlus

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Collapse All How many people are diagnosed with HIV each year in the United States? In 2014, ...

  9. HIV Medicines and Side Effects

    MedlinePlus

    Side Effects of HIV Medicines HIV Medicines and Side Effects (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points HIV medicines help people with ... will depend on a person’s individual needs. Can HIV medicines cause side effects? HIV medicines help people ...

  10. Audit Report, "Fire Protection Deficiencies at Los Alamos National Laboratory"

    SciTech Connect

    2009-06-01

    The Department of Energy's Los Alamos National Laboratory (Los Alamos) maintains some of the Nation's most important national security assets, including nuclear materials. Many of Los Alamos' facilities are located in close proximity to one another, are occupied by large numbers of contract and Federal employees, and support activities ranging from nuclear weapons design to science-related activities. Safeguarding against fires, regardless of origin, is essential to protecting employees, surrounding communities, and national security assets. On June 1, 2006, Los Alamos National Security, LLC (LANS), became the managing and operating contractor for Los Alamos, under contract with the Department's National Nuclear Security Administration (NNSA). In preparation for assuming its management responsibilities at Los Alamos, LANS conducted walk-downs of the Laboratory's facilities to identify pre-existing deficiencies that could give rise to liability, obligation, loss or damage. The walk-downs, which identified 812 pre-existing fire protection deficiencies, were conducted by subject matter professionals, including fire protection experts. While the Los Alamos Site Office has overall responsibility for the effectiveness of the fire protection program, LANS, as the Laboratory's operating contractor, has a major, day-to-day role in minimizing fire-related risks. The issue of fire protection at Los Alamos is more than theoretical. In May 2000, the 'Cerro Grande' fire burned about 43,000 acres, including 7,700 acres of Laboratory property. Due to the risk posed by fire to the Laboratory's facilities, workforce, and surrounding communities, we initiated this audit to determine whether pre-existing fire protection deficiencies had been addressed. Our review disclosed that LANS had not resolved many of the fire protection deficiencies that had been identified in early 2006: (1) Of the 296 pre-existing deficiencies we selected for audit, 174 (59 percent) had not been corrected

  11. HIV infection among U.S. Army and Air Force military personnel: sociodemographic and genotyping analysis.

    PubMed

    Singer, Darrell E; Bautista, Christian T; O'Connell, Robert J; Sanders-Buell, Eric; Agan, Brian K; Kijak, Gustavo H; Hakre, Shilpa; Sanchez, Jose L; Sateren, Warren B; McCutchan, Francine E; Michael, Nelson L; Scott, Paul T

    2010-08-01

    Since 1985, the U.S. Department of Defense has periodically screened all military personnel for HIV allowing for the monitoring of the infection in this dynamic cohort population. A nested case-control study was performed to study sociodemographics, overseas assignment, and molecular analysis of HIV. Cases were newly identified HIV infections among U.S. Army and Air Force military personnel from 2000 to 2004. Controls were frequency matched to cases by gender and date of case first positive HIV screening test. Genotyping analysis was performed using high-throughput screening assays and partial genome sequencing. HIV was significantly associated with black race [odds ratio (OR) = 6.65], single marital status (OR = 4.45), and age (OR per year = 1.07). Ninety-seven percent were subtype B and 3% were non-B subtypes (A3, CRF01_AE, A/C recombinant, G, CRF02_AG). Among cases, overseas assignment in the period at risk prior to their first HIV-positive test was associated with non-B HIV subtype infection (OR = 8.44). Black and single military personnel remain disproportionately affected by HIV infection. Most non-B HIV subtypes were associated with overseas assignment. Given the increased frequency and length of assignments, and the expanding HIV genetic diversity observed in this population, there is a need for active HIV genotyping surveillance and a need to reinforce primary HIV prevention efforts.

  12. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection

    PubMed Central

    Wagner, Thor A.; McLaughlin, Sherry; Garg, Kavita; Cheung, Charles Y. K.; Larsen, Brendan B.; Styrchak, Sheila; Huang, Hannah C.; Edlefsen, Paul T.; Mullins, James I.; Frenkel, Lisa M.

    2014-01-01

    Antiretroviral treatment (ART) of HIV infection suppresses viral replication. Yet if ART is stopped, virus reemerges because of the persistence of infected cells. We evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. A total of 534 HIV integration sites (IS) and 63 adjacent HIV env sequences were derived from three study participants over 11.3 to 12.7 years of ART. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. Integrations were overrepresented in genes associated with cancer and favored in 12 genes across multiple participants. Over time on ART, a greater proportion of persisting proviruses were in proliferating cells. HIV integration into specific genes may promote proliferation of HIV-infected cells, slowing viral decay during ART. PMID:25011556

  13. Types of HIV/AIDS Antiretroviral Drugs

    MedlinePlus

    ... reverse transcriptase (RT) from converting single-stranded HIV RNA into double-stranded HIV DNA―a process called ... RT, interfering with its ability to convert HIV RNA into HIV DNA Integrase Inhibitors block the HIV ...

  14. Natural Attenuation of Anthropogenic Chromium in Selected Puye Formation in Regional Aquifer System of LOS Alamos, New Mexico

    NASA Astrophysics Data System (ADS)

    Brown, D. B.; Ding, M.; WoldeGabriel, G. W.; Cheshire, M.; Rearick, M.; Conradson, S.; Kluk, E.; Katzman, D.

    2014-12-01

    Routine groundwater monitoring conducted in 2005 revealed significant chromium (Cr) contamination in regional groundwater in Los Alamos, New Mexico. Previous use of potassium dichromate (K2Cr2O7) in cooling towers at Los Alamos National Laboratory's main power plant is believed to be the source of the elevated chromium levels. From 1956 to 1972 between 31,000 and 72,000 Kg of toxic Cr(IV) was released into Sandia Canyon. Initial investigations of the vadose zone using chromium isotopes indicated that reduction of anthropogenic Cr(IV) had occurred. However, to justify the use of Monitoring Natural Attenuation (MNA) as a valid remediation strategy, the Cr attenuation mechanism and the reduction capacity of the regional aquifer needs to be determined. Conventional batch sorption and synchrotron-based X-ray absorption spectroscopy studies were performed. Two samples were selected from the Puye formation, a silicoclastic sedimentary rock sequence located within the contaminated aquifer. Additionally, two Los Alamos Puye outcrop samples with no chromium exposure were selected for comparison. Each sample was subsequently sorted based on grain size, magnetic, and clay fractions. Groundwater with a known concentration of Cr(IV) was used in the batch experiments. Spectroscopy measurements of Puye samples before and after exposure to the same contaminated groundwater were conducted at the Stanford Synchrotron Radiation Lightsource (SSRL). Batch sorption results indicated little to no attenuation, as indicated by the small measured sorption coefficient (Kd < 5 Kg/L). Spectroscopic measurements suggest that attenuation of hexavalent chromium in groundwater is due to reduction of Cr(VI) to Cr(III) in the Puye and may be attributed almost exclusively to the clay fraction. These results indicate that the tested Puye sediments occurring in the regional aquifer have minor ability to naturally attenuate anthropogenic Cr(IV), with the clay fraction dominating the reduction process

  15. Groundwater Level Status Report for 2005 Los Alamos National Laboratory

    SciTech Connect

    S.P. Allen; R.J. Koch

    2006-05-15

    The status of groundwater level monitoring at Los Alamos National Laboratory (LANL) in 2005 is provided in this report. The Groundwater Level Monitoring Project was instituted in 2005 to provide a framework for the collection and processing of quality controlled groundwater level data. This report summarizes groundwater level data for 137 monitoring wells, including 41 regional aquifer wells, 22 intermediate wells, and 74 alluvial wells. Pressure transducers were installed in 118 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well.

  16. Decommissioning of surplus facilities at Los Alamos National Laboratory

    SciTech Connect

    Stout, D.S.

    1995-03-01

    Decommissioning Buildings 3 and 4 South at Technical Area 21, Los Alamos National Laboratory, involves the decontamination, dismantlement, and demolition of two enriched-uranium processing buildings containing process equipment and ductwork holdup. The Laboratory has adopted two successful management strategies to implement this project: Rather than characterize an entire site, upfront, investigators use the ``observational approach,`` in which they collect only enough data to begin decommissioning activities and then determine appropriate procedures for further characterization as the work progresses. Project leaders augment work packages with task hazard analyses to fully define specific tasks and inform workers of hazards; all daily work activities are governed by specific work procedures and hazard analyses.

  17. End magnets for the NBS-Los Alamos racetrack microtron

    SciTech Connect

    Debenham, P.H.; Lindstrom, E.R.; Mohr, D.L.

    1983-01-01

    Two end magnets have been designed and constructed for the 185 MeV NBS-Los Alamos racetrack microtron. The field has been measured in the first magnet and is uniform over a 0.62 m/sup 2/ area to within +-2 x 10/sup -4/ at 1 T. The magnet meets all performance specifications. Field measurements are underway on the second magnet. In this paper, design and construction details which play an important role in magnetic performance are described, and the measured fields are compared with calculations.

  18. Mac configuration management at the Los Alamos National Laboratory

    SciTech Connect

    Marcus, Allan B

    2010-01-01

    The Los Alamos National Laboratory (LANL) had a need for central configuration management of non-Windows computers. LANL has three to five thousand Macs and an equal number of Linux based systems. The primary goal was to be able to inventory all non-windows systems and patch Mc OS X systems. LANL examined a number of commercial and open source solutions and ultimately selected Puppet. This paper will discuss why we chose Puppet, how we implemented it, and some lessons we learned along the way.

  19. Theoretical atomic physics code development at Los Alamos

    SciTech Connect

    Clark, R.E.H.; Abdallah, J. Jr.

    1989-01-01

    We have developed a set of computer codes for atomic physics calculations at Los Alamos. These codes can calculate a large variety of data with a minimum of effort on the part of the user. In particular, differential cross sections and electron impact coherence parameters can be readily obtained for arbitrary ions or atoms. Currently, the theory consists of non-relativistic Hartree-Fock structure calculations and non relativistic distorted wave approximation or first order many body theory collisional calculations. 12 refs., 2 figs., 5 tabs.

  20. Groundwater level status report for 2010, Los Alamos National Laboratory

    SciTech Connect

    Koch, Richard J.; Schmeer, Sarah

    2011-03-01

    The status of groundwater level monitoring at Los Alamos National Laboratory in 2010 is provided in this report. This report summarizes groundwater level data for 194 monitoring wells, including 63 regional aquifer wells (including 10 regional/intermediate wells), 34 intermediate wells, 97 alluvial wells, and 12 water supply wells. Pressure transducers were installed in 162 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well. The report also summarizes the groundwater temperatures recorded in intermediate and regional aquifer monitoring wells and seasonal responses to snowmelt runoff observed in intermediate wells.

  1. The Los Alamos National Laboratory Nuclear Vision Project

    SciTech Connect

    Arthur, E.D.; Wagner, R.L. Jr.

    1996-09-01

    Los Alamos National Laboratory has initiated a project to examine possible futures associated with the global nuclear enterprise over the course of the next 50 years. All major components are included in this study--weapons, nonproliferation, nuclear power, nuclear materials, and institutional and public factors. To examine key issues, the project has been organized around three main activity areas--workshops, research and analyses, and development of linkages with other synergistic world efforts. This paper describes the effort--its current and planned activities--as well as provides discussion of project perspectives on nuclear weapons, nonproliferation, nuclear energy, and nuclear materials focus areas.

  2. Los Alamos safeguards program overview and NDA in safeguards

    SciTech Connect

    Keepin, G.R.

    1988-01-01

    Over the years the Los Alamos safeguards program has developed, tested, and implemented a broad range of passive and active nondestructive analysis (NDA) instruments (based on gamma and x-ray detection and neutron counting) that are now widely employed in safeguarding nuclear materials of all forms. Here very briefly, the major categories of gamma ray and neutron based NDA techniques, give some representative examples of NDA instruments currently in use, and cite a few notable instances of state-of-the-art NDA technique development. Historical aspects and a broad overview of the safeguards program are also presented.

  3. Tiger Team Assessment of the Los Alamos National Laboratory

    SciTech Connect

    Not Available

    1991-11-01

    The purpose of the safety and health assessment was to determine the effectiveness of representative safety and health programs at the Los Alamos National Laboratory (LANL). Within the safety and health programs at LANL, performance was assessed in the following technical areas: Organization and Administration, Quality Verification, Operations, Maintenance, Training and Certification, Auxiliary Systems, Emergency Preparedness, Technical Support, Packaging and Transportation, Nuclear Criticality Safety, Security/Safety Interface, Experimental Activities, Site/Facility Safety Review, Radiological Protection, Personnel Protection, Worker Safety and Health (OSHA) Compliance, Fire Protection, Aviation Safety, Explosives Safety, Natural Phenomena, and Medical Services.

  4. Los Alamos Science, Number 25 -- 1997: Celebrating the neutrino

    SciTech Connect

    Cooper, N.G.

    1997-12-31

    This issue is devoted to the neutrino and its remaining mysteries. It is divided into the following areas: (1) The Reines-Cowan experiment -- detecting the poltergeist; (2) The oscillating neutrino -- an introduction to neutrino masses and mixing; (3) A brief history of neutrino experiments at LAMPF; (4) A thousand eyes -- the story of LSND (Los Alamos neutrino oscillation experiment); (5) The evidence for oscillations; (6) The nature of neutrinos in muon decay and physics beyond the Standard Model; (7) Exorcising ghosts -- in pursuit of the missing solar neutrinos; (8) MSW -- a possible solution to the solar neutrino problem; (8) Neutrinos and supernovae; and (9) Dark matter and massive neutrinos.

  5. Recent developments in the Los Alamos radiation transport code system

    SciTech Connect

    Forster, R.A.; Parsons, K.

    1997-06-01

    A brief progress report on updates to the Los Alamos Radiation Transport Code System (LARTCS) for solving criticality and fixed-source problems is provided. LARTCS integrates the Diffusion Accelerated Neutral Transport (DANT) discrete ordinates codes with the Monte Carlo N-Particle (MCNP) code. The LARCTS code is being developed with a graphical user interface for problem setup and analysis. Progress in the DANT system for criticality applications include a two-dimensional module which can be linked to a mesh-generation code and a faster iteration scheme. Updates to MCNP Version 4A allow statistical checks of calculated Monte Carlo results.

  6. Upgrade of the Los Alamos Plutonium Facility control system

    SciTech Connect

    Pope, N.G.; Turner, W.J.; Brown, R.E.; Bibeau, R.A.; Davis, R.R.; Hogan, K.

    1996-05-01

    After 20 yrs service, the Los Alamos Plutonium Facility is undergoing an upgrade to its aging Facility Control System. The new system design includes a network of redundantly-paired programmable logic controllers that will interface with about 2200 field data points. The data communications network that has been designed includes a redundant, self-healing fiber optic data highway as well as a fiber optic ethernet. Commercially available human-machine interface software running on a UNIX-based system displays facility subsystem status operator X-terminals. Project design features, methods, costs, and schedule are discussed.

  7. Groundwater level status report for 2008, Los Alamos National Laboratory

    SciTech Connect

    Koch, Richard J.; Schmeer, Sarah

    2009-03-01

    The status of groundwater level monitoring at Los Alamos National Laboratory in 2008 is provided in this report. This report summarizes groundwater level data for 179 monitoring wells, including 45 regional aquifer wells, 28 intermediate wells, 8 regional/intermediate wells, 106 alluvial wells, and 12 water supply wells. Pressure transducers were installed in 166 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well. The report also summarizes the groundwater temperatures recorded in intermediate and regional aquifer monitoring wells.

  8. Groundwater level status report for 2009, Los Alamos National Laboratory

    SciTech Connect

    Koch, Richard J.; Schmeer, Sarah

    2010-03-01

    The status of groundwater level monitoring at Los Alamos National Laboratory in 2009 is provided in this report. This report summarizes groundwater level data for 179 monitoring wells, including 55 regional aquifer wells (including 11 regional/intermediate wells), 26 intermediate wells, 98 alluvial wells, and 12 water supply wells. Pressure transducers were installed in 161 monitoring wells for continuous monitoring of groundwater levels. Time-series hydrographs of groundwater level data are presented along with pertinent construction and location information for each well. The report also summarizes the groundwater temperatures recorded in intermediate and regional aquifer monitoring wells.

  9. Water supply at Los Alamos during 1985: Progress report

    SciTech Connect

    Purtymun, W.D.; Becker, N.M.; Maes, M.N.

    1986-10-01

    Well field operations during 1985 were satisfactory with municipal and industrial supplies consisting of 1587 x 10/sup 6/ gal from wells in three well fields and 37 x 10/sup 6/ gal from the gallery in Water Canyon. About 2.8 x 10/sup 6/ gal of water from Guaje Reservoir and 0.9 x 10/sup 6/ gal from Los Alamos Reservoir were used for irrigation; thus the total water usage in 1985 was about 1628 x 10/sup 6/ gal. Primary and secondary chemical quality of water in the distribution system is in compliance with federal regulations.

  10. Quasispecies Analyses of the HIV-1 Near-full-length Genome With Illumina MiSeq.

    PubMed

    Ode, Hirotaka; Matsuda, Masakazu; Matsuoka, Kazuhiro; Hachiya, Atsuko; Hattori, Junko; Kito, Yumiko; Yokomaku, Yoshiyuki; Iwatani, Yasumasa; Sugiura, Wataru

    2015-01-01

    Human immunodeficiency virus type-1 (HIV-1) exhibits high between-host genetic diversity and within-host heterogeneity, recognized as quasispecies. Because HIV-1 quasispecies fluctuate in terms of multiple factors, such as antiretroviral exposure and host immunity, analyzing the HIV-1 genome is critical for selecting effective antiretroviral therapy and understanding within-host viral coevolution mechanisms. Here, to obtain HIV-1 genome sequence information that includes minority variants, we sought to develop a method for evaluating quasispecies throughout the HIV-1 near-full-length genome using the Illumina MiSeq benchtop deep sequencer. To ensure the reliability of minority mutation detection, we applied an analysis method of sequence read mapping onto a consensus sequence derived from de novo assembly followed by iterative mapping and subsequent unique error correction. Deep sequencing analyses of aHIV-1 clone showed that the analysis method reduced erroneous base prevalence below 1% in each sequence position and discarded only < 1% of all collected nucleotides, maximizing the usage of the collected genome sequences. Further, we designed primer sets to amplify the HIV-1 near-full-length genome from clinical plasma samples. Deep sequencing of 92 samples in combination with the primer sets and our analysis method provided sufficient coverage to identify >1%-frequency sequences throughout the genome. When we evaluated sequences of pol genes from 18 treatment-naïve patients' samples, the deep sequencing results were in agreement with Sanger sequencing and identified numerous additional minority mutations. The results suggest that our deep sequencing method would be suitable for identifying within-host viral population dynamics throughout the genome. PMID:26617593

  11. Temporal analysis of the antibody response to HIV envelope protein in HIV-infected laboratory workers.

    PubMed

    Pincus, S H; Messer, K G; Nara, P L; Blattner, W A; Colclough, G; Reitz, M

    1994-06-01

    Three laboratory workers have been infected with the IIIB strain of HIV; their antibody response to HIV has been studied in serial serum specimens. Because the infecting virus is known, the fine specificity of the antibody response was studied on the homologous strain of HIV. Anti-p17, anti-p24, anti-gp160, CD4/gp120 blocking and neutralizing antibodies developed in parallel. Epitope mapping of the anti-gp160 response indicated several regions that consistently induced an antibody response. Serum contained antibody which reacted with V3-specific peptides corresponding to the very tip of the loop and crossreactivity was seen with V3 loop peptides from other sequence divergent strains of HIV. Antibody to the V1 loop was produced at levels comparable with that seen for the V3-loop. Anti-V1 neutralized HIV with a titration curve equivalent to an anti-V3 monoclonal antibody. Because the infecting virus is known and serial reisolates have been obtained, we explored the relationship between production of antibody to a given epitope and mutation in the virus. The data suggest that an association exists, but do not clearly indicate that antibody drives the selection for mutant viruses. The findings presented here provide a fine specificity analysis of the evolution of the antibody response to HIV in greater detail than has previously been performed.

  12. Frequent intra-subtype recombination among HIV-1 circulating in Tanzania.

    PubMed

    Kiwelu, Ireen E; Novitsky, Vladimir; Margolin, Lauren; Baca, Jeannie; Manongi, Rachel; Sam, Noel; Shao, John; McLane, Mary F; Kapiga, Saidi H; Essex, M

    2013-01-01

    The study estimated the prevalence of HIV-1 intra-subtype recombinant variants among female bar and hotel workers in Tanzania. While intra-subtype recombination occurs in HIV-1, it is generally underestimated. HIV-1 env gp120 V1-C5 quasispecies from 45 subjects were generated by single-genome amplification and sequencing (median (IQR) of 38 (28-50) sequences per subject). Recombination analysis was performed using seven methods implemented within the recombination detection program version 3, RDP3. HIV-1 sequences were considered recombinant if recombination signals were detected by at least three methods with p-values of ≤0.05 after Bonferroni correction for multiple comparisons. HIV-1 in 38 (84%) subjects showed evidence for intra-subtype recombination including 22 with HIV-1 subtype A1, 13 with HIV-1 subtype C, and 3 with HIV-1 subtype D. The distribution of intra-patient recombination breakpoints suggested ongoing recombination and showed selective enrichment of recombinant variants in 23 (60%) subjects. The number of subjects with evidence of intra-subtype recombination increased from 29 (69%) to 36 (82%) over one year of follow-up, although the increase did not reach statistical significance. Adjustment for intra-subtype recombination is important for the analysis of multiplicity of HIV infection. This is the first report of high prevalence of intra-subtype recombination in the HIV/AIDS epidemic in Tanzania, a region where multiple HIV-1 subtypes co-circulate. HIV-1 intra-subtype recombination increases viral diversity and presents additional challenges for HIV-1 vaccine design. PMID:23940702

  13. Detecting primary drug-resistant mutations in Korean HIV patients using ultradeep pyrosequencing.

    PubMed

    Cho, Min-Chul; Park, Chang-Wook; Park, Borae G; Oh, Heung-Bum; Choi, Sang-Ho; Choi, Sung-Eun; Cho, Nam-Sun

    2016-08-01

    HIV primary resistance, drug resistance in treatment-naïve patients, is an emerging public health issue. The prevalence of HIV primary resistance mutations down to the level of 1% minor variants was investigated using ultradeep pyrosequencing (UDPS) in HIV-positive Korean blood donors and in treatment naïve chronic patients for the comparison. The entire pol region was sequenced from 25 HIV-positive blood donors, and 18 treatment-naïve chronic HIV patients. UDPS was successful in 19 blood donors and 18 chronic patients. In total, 1,011,338 sequence reads were aligned, and 28,093 sequence reads were aligned on average per sample. The prevalence of HIV primary resistance mutations in the HIV-positive blood donors and chronic HIV patients were 63.2% and 44.4% according to UDPS, respectively. Protease inhibitor (PI) drugs demonstrated different patterns in HIV-positive blood donors and chronic HIV patients, whereas non-nucleoside reverse transcriptase inhibitors (NNRTI), nucleoside reverse transcriptase inhibitors (NRTI), and integrase inhibitor (INI) drugs showed similar patterns between the two groups. Higher level of primary resistance prevalence was observed mainly because UDPS method could detect mutations in minor variants with 1-10% frequency. The higher resistance prevalence was observed in HIV-positive blood donors than in chronic patients. Considering that treatments for HIV-infected patients were recently amended to start at an earlier stage, information about degree of drug resistance to each drug between the two groups would help to establish future policies, design additional clinical trials, assess HIV patient care in Korea. PMID:27109046

  14. Alterations in the gut microbiota associated with HIV-1 infection.

    PubMed

    Lozupone, Catherine A; Li, Marcella; Campbell, Thomas B; Flores, Sonia C; Linderman, Derek; Gebert, Matthew J; Knight, Rob; Fontenot, Andrew P; Palmer, Brent E

    2013-09-11

    Understanding gut microbiota alterations associated with HIV infection and factors that drive these alterations may help explain gut-linked diseases prevalent with HIV. 16S rRNA sequencing of feces from HIV-infected individuals revealed that HIV infection is associated with highly characteristic gut community changes, and antiretroviral therapy does not consistently restore the microbiota to an HIV-negative state. Despite the chronic gut inflammation characteristic of HIV infection, the associated microbiota showed limited similarity with other inflammatory states and instead showed increased, rather than decreased, diversity. Meta-analysis revealed that the microbiota of HIV-infected individuals in the U.S. was most similar to a Prevotella-rich community composition typically observed in healthy individuals in agrarian cultures of Malawi and Venezuela and related to that of U.S. individuals with carbohydrate-rich, protein- and fat-poor diets. By evaluating innate and adaptive immune responses to lysates from bacteria that differ with HIV, we explore the functional drivers of these compositional differences. PMID:24034618

  15. Genetic diversity of HIV type 1 in Montenegro.

    PubMed

    Ciccozzi, Massimo; Vujošević, Danijela; Lo Presti, Alessandra; Mugoša, Boban; Vratnica, Zoran; Lai, Alessia; Laušević, Dragan; Drašković, Nenad; Marjanovic, Aleksandra; Cella, Eleonora; Santoro, Maria M; Alteri, Claudia; Fabeni, Lavinia; Ciotti, Marco; Zehender, Gianguglielmo

    2011-08-01

    Human immunodeficiency virus type 1 (HIV-1) is characterized by high genetic variability due to its high replication rate and the lack of proofreading activity of the reverse transcriptase enzyme. On the basis of phylogenetic analysis performed on numerous isolates from all over the world, HIV-1 is subdivided into types, subtypes, subsubtypes, circulating recombinant forms, and unique recombinant forms. No data are currently available about the circulation of HIV-1 types in Montenegro. Here, we describe the genetic variability of HIV-1 strains identified in plasma samples of patients from Montenegro. Phylogenetic analysis on 32 HIV-1 sequences was carried out. The prevalent circulating HIV-1 subtype is B. The strains were interspersed within the tree. Two main clades (I and II) may suggest independent introductions of HIV-1 subtype B into Montenegro, although other epidemiological evidence will be needed to assume a small number of introductions. No obvious evidence of clustering by residence, age, or sex was found (data not shown). Nelfinavir resistance was found, though lopinavir is the only PI administered. Continuous monitoring of HIV-1-infected individuals is crucial to a better understand of the epidemiology of the B subtype in Montenegro.

  16. [A new unique HIV-1 recombinant form detected in Belarus].

    PubMed

    Eremin, V F; Gasich, E L; Sosinovich, S V

    2012-01-01

    Republican Research-and-Practical Center for Epidemiology and Microbiology, Ministry of Health of Belarus, Minsk The paper presents data on the molecular genetic characteristics of a new HIV-1 recombinant form. The study has shown that the virus is referred to as HIV-1 subtype B in terms of the gag gene and HIV-1 subtype A in terms of the pol and env genes. At the same time the new isolate is closer, in terms of the gag gene, to the HIV-1 DQ207943 strain isolated in Georgia, in terms of the pol gene, to the HIV-1 AF413987.1 strain isolated in Ukraine and, in terms of the env gene to the HIV-1 AY500393 strain isolated in Russia. Thus, the described new HIV-1 recombinant form has the following structure: BgagApolAenv. The gag, pol, and env gene sequences from the new unique HIV-1 recombinant form have been registered in the international database EMBL/Genbank/DDBJ under accession numbers FR775442.1, FN995656.1, and FR775443.1.

  17. Retroviral DNA Integration Directed by HIV Integration Protein in Vitro

    NASA Astrophysics Data System (ADS)

    Bushman, Frederic D.; Fujiwara, Tamio; Craigie, Robert

    1990-09-01

    Efficient retroviral growth requires integration of a DNA copy of the viral RNA genome into a chromosome of the host. As a first step in analyzing the mechanism of integration of human immunodeficiency virus (HIV) DNA, a cell-free system was established that models the integration reaction. The in vitro system depends on the HIV integration (IN) protein, which was partially purified from insect cells engineered to express IN protein in large quantities. Integration was detected in a biological assay that scores the insertion of a linear DNA containing HIV terminal sequences into a λ DNA target. Some integration products generated in this assay contained five-base pair duplications of the target DNA at the recombination junctions, a characteristic of HIV integration in vivo; the remaining products contained aberrant junctional sequences that may have been produced in a variation of the normal reaction. These results indicate that HIV IN protein is the only viral protein required to insert model HIV DNA sequences into a target DNA in vitro.

  18. HIV/AIDS and Alcohol

    MedlinePlus

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). Each year in the United States, between 55, ...

  19. HIV / AIDS: An Unequal Burden

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 Table ... Victoria Cargill talks to students about HIV and AIDS at the opening of a National Library of ...

  20. HIV, AIDS, and the Future

    MedlinePlus

    ... Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV, AIDS, and the Future Past Issues / Summer 2009 Table ... and your loved ones from HIV/AIDS. The AIDS Memorial Quilt In 1987, a total of 1, ...

  1. Women and HIV/AIDS

    MedlinePlus

    ... action on HIV/AIDS National Women and Girls HIV/AIDS Awareness Day – March 10 Programs Share your story Anonymous from Illinois says... Although I am HIV negative, I would like to share my story. ...

  2. HIV/AIDS in Women

    MedlinePlus

    HIV, the human immunodeficiency virus, kills or damages cells of the body's immune system. The most advanced stage of infection with HIV is AIDS, which stands for acquired immunodeficiency syndrome. HIV often ...

  3. TALEN gene editing takes aim on HIV.

    PubMed

    Benjamin, Ronald; Berges, Bradford K; Solis-Leal, Antonio; Igbinedion, Omoyemwen; Strong, Christy L; Schiller, Martin R

    2016-09-01

    Transcription activator-like effector nucleases (TALENs) are one of several types of programmable, engineered nucleases that bind and cleave specific DNA sequences. Cellular machinery repairs the cleaved DNA by introducing indels. In this review, we emphasize the potential, explore progress, and identify challenges in using TALENs as a therapeutic tool to treat HIV infection. TALENs have less off-target editing and can be more effective at tolerating HIV escape mutations than CRISPR/Cas-9. Scientists have explored TALEN-mediated editing of host genes such as viral entry receptors (CCR5 and CXCR4) and a protein involved in proviral integration (LEDGF/p75). Viral targets include the proviral DNA, particularly focused on the long terminal repeats. Major challenges with translating gene therapy from bench to bedside are improving cleavage efficiency and delivery, while minimizing off-target editing, cytotoxicity, and immunogenicity. However, rapid improvements in TALEN technology are enhancing cleavage efficiency and specificity. Therapeutic testing in animal models of HIV infection will help determine whether TALENs are a viable HIV treatment therapy. TALENs or other engineered nucleases could shift the therapeutic paradigm from life-long antiretroviral therapy toward eradication of HIV infection.

  4. HIV Type 1 Transmission Networks Among Men Having Sex with Men and Heterosexuals in Kenya

    PubMed Central

    Faria, Nuno Rodrigues; Hassan, Amin; Hamers, Raph L.; Mutua, Gaudensia; Anzala, Omu; Mandaliya, Kishor; Cane, Patricia; Berkley, James A.; Rinke de Wit, Tobias F.; Wallis, Carole; Graham, Susan M.; Price, Matthew A.; Coutinho, Roel A.; Sanders, Eduard J.

    2014-01-01

    Abstract We performed a molecular phylogenetic study on HIV-1 polymerase sequences of men who have sex with men (MSM) and heterosexual patient samples in Kenya to characterize any observed HIV-1 transmission networks. HIV-1 polymerase sequences were obtained from samples in Nairobi and coastal Kenya from 84 MSM, 226 other men, and 364 women from 2005 to 2010. Using Bayesian phylogenetics, we tested whether sequences clustered by sexual orientation and geographic location. In addition, we used trait diffusion analyses to identify significant epidemiological links and to quantify the number of transmissions between risk groups. Finally, we compared 84 MSM sequences with all HIV-1 sequences available online at GenBank. Significant clustering of sequences from MSM at both coastal Kenya and Nairobi was found, with evidence of HIV-1 transmission between both locations. Although a transmission pair between a coastal MSM and woman was confirmed, no significant HIV-1 transmission was evident between MSM and the comparison population for the predominant subtype A (60%). However, a weak but significant link was evident when studying all subtypes together. GenBank comparison did not reveal other important transmission links. Our data suggest infrequent intermingling of MSM and heterosexual HIV-1 epidemics in Kenya. PMID:23947948

  5. Barriers to HIV Cure.

    PubMed

    Stein, J; Storcksdieck Genannt Bonsmann, M; Streeck, H

    2016-10-01

    Since the beginning of the epidemic, more than 70 million people have been infected with human immunodeficiency virus (HIV) and about 38 million have died from acquired immune deficiency syndrome (AIDS)-related illnesses. While the discovery of highly active antiretroviral therapy (HAART) in the mid 90's has saved millions of lives, a complete eradication of HIV is still not possible as HIV can persist for decades in a small reservoir of latently infected cells. Once reactivated, these latently infected cells can actively produce viral particles. Recent studies suggest that several sanctuaries exist within infected individuals where HIV can remain undetected by the immune system. These cellular, anatomical and microanatomical viral reservoirs represent a major obstacle for the eradication of HIV. Here we review recent findings on potential sanctuaries of HIV and address potential avenues to overcome these immunological barriers. PMID:27620852

  6. The Los Alamos suite of relativistic atomic physics codes

    SciTech Connect

    Fontes, C. J.; Zhang, H. L.; Jr, J. Abdallah; Clark, R. E. H.; Kilcrease, D. P.; Colgan, J.; Cunningham, R. T.; Hakel, P.; Magee, N. H.; Sherrill, M. E.

    2015-05-28

    The Los Alamos SuitE of Relativistic (LASER) atomic physics codes is a robust, mature platform that has been used to model highly charged ions in a variety of ways. The suite includes capabilities for calculating data related to fundamental atomic structure, as well as the processes of photoexcitation, electron-impact excitation and ionization, photoionization and autoionization within a consistent framework. These data can be of a basic nature, such as cross sections and collision strengths, which are useful in making predictions that can be compared with experiments to test fundamental theories of highly charged ions, such as quantum electrodynamics. The suite can also be used to generate detailed models of energy levels and rate coefficients, and to apply them in the collisional-radiative modeling of plasmas over a wide range of conditions. Such modeling is useful, for example, in the interpretation of spectra generated by a variety of plasmas. In this work, we provide a brief overview of the capabilities within the Los Alamos relativistic suite along with some examples of its application to the modeling of highly charged ions.

  7. Industrial application for the Los Alamos Materials Modeling Platform

    SciTech Connect

    Lesar, R.; Charbon, C.; Kothe, D.; Wu, D.; Reddy, A.

    1996-09-01

    This is the final report of a one-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Casting and solidification of molten metals and metal alloys is a critical step in the production of high-quality metal stock and in the fabrication of finished parts. Control of the casting process can be the determining factor in both the quality and cost of the final metal product. Major problems with the quality of cast stock or finished parts can arise because of the difficulty of preventing variations in the alloy content, the generation of porosity or poor surface finish, and the loss of microstructure controlled strength and toughness resulting from the poor understanding and design of the mold filling and solidification processes. In this project, we sought to develop a new set of applications focused on adding the ability to accurately model solidification and grain growth to casting simulations. We implemented these applications within the Los Alamos Materials Modeling Platform, LAMMP, a graphical-based materials, and materials modeling environment being created at the Computational Testbed for Industry.

  8. The Los Alamos suite of relativistic atomic physics codes

    DOE PAGES

    Fontes, C. J.; Zhang, H. L.; Jr, J. Abdallah; Clark, R. E. H.; Kilcrease, D. P.; Colgan, J.; Cunningham, R. T.; Hakel, P.; Magee, N. H.; Sherrill, M. E.

    2015-05-28

    The Los Alamos SuitE of Relativistic (LASER) atomic physics codes is a robust, mature platform that has been used to model highly charged ions in a variety of ways. The suite includes capabilities for calculating data related to fundamental atomic structure, as well as the processes of photoexcitation, electron-impact excitation and ionization, photoionization and autoionization within a consistent framework. These data can be of a basic nature, such as cross sections and collision strengths, which are useful in making predictions that can be compared with experiments to test fundamental theories of highly charged ions, such as quantum electrodynamics. The suitemore » can also be used to generate detailed models of energy levels and rate coefficients, and to apply them in the collisional-radiative modeling of plasmas over a wide range of conditions. Such modeling is useful, for example, in the interpretation of spectra generated by a variety of plasmas. In this work, we provide a brief overview of the capabilities within the Los Alamos relativistic suite along with some examples of its application to the modeling of highly charged ions.« less

  9. The Los Alamos universe: Using multimedia to promote laboratory capabilities

    SciTech Connect

    Kindel, J.

    2000-03-01

    This project consists of a multimedia presentation that explains the technological capabilities of Los Alamos National Laboratory. It takes the form of a human-computer interface built around the metaphor of the universe. The project is intended promote Laboratory capabilities to a wide audience. Multimedia is simply a means of communicating information through a diverse set of tools--be they text, sound, animation, video, etc. Likewise, Los Alamos National Laboratory is a collection of diverse technologies, projects, and people. Given the ample material available at the Laboratory, there are tangible benefits to be gained by communicating across media. This paper consists of three parts. The first section provides some basic information about the Laboratory, its mission, and its needs. The second section introduces this multimedia presentation and the metaphor it is based on along with some basic concepts of color and user interaction used in the building of this project. The final section covers construction of the project, pitfalls, and future improvements.

  10. Solar pond research at the Los Alamos National Laboratory

    SciTech Connect

    Jones, G.F.; Meyer, K.A.; Hedstrom, J.C.; Grimmer, D.P.

    1984-01-01

    A description of solar pond research at Los Alamos National Laboratory is presented. The main issues in the theory of solar ponds are discussed. Among these are the interfacial-boundary-layer model, models for interface motion and pond performance, heat extraction, and ground heat loss. The core of the research effort at Los Alamos was the development of a one-dimensional computer program to accurately predict dynamic performance of a solar pond. The computer model and the experiments that were designed and performed to validate it are described. The experiments include two laboratory tanks wherein temperature, salinity, and flow visualization data were obtained and a 232 m/sup 2/ outdoor solar pond. Results from preliminary validation show good agreement between the pond's predicted dynamic behavior and that which actually occurred in the experiments. More validation using data from full-sized solar ponds is needed. A new correlation for the ratio of interfacial salt-flux to heat-flux is proposed which agrees well with our data. Recommendations for future research are given.

  11. Los Alamos Center for Computer Security formal computer security model

    SciTech Connect

    Dreicer, J.S.; Hunteman, W.J.; Markin, J.T.

    1989-01-01

    This paper provides a brief presentation of the formal computer security model currently being developed at the Los Alamos Department of Energy (DOE) Center for Computer Security (CCS). The need to test and verify DOE computer security policy implementation first motivated this effort. The actual analytical model was a result of the integration of current research in computer security and previous modeling and research experiences. The model is being developed to define a generic view of the computer and network security domains, to provide a theoretical basis for the design of a security model, and to address the limitations of present formal mathematical models for computer security. The fundamental objective of computer security is to prevent the unauthorized and unaccountable access to a system. The inherent vulnerabilities of computer systems result in various threats from unauthorized access. The foundation of the Los Alamos DOE CCS model is a series of functionally dependent probability equations, relations, and expressions. The model is undergoing continued discrimination and evolution. We expect to apply the model to the discipline of the Bell and LaPadula abstract sets of objects and subjects. 6 refs.

  12. Fuels Inventories in the Los Alamos National Laboratory Region: 1997

    SciTech Connect

    Balice, R.G.; Oswald, B.P.; Martin, C.

    1999-03-01

    Fifty-four sites were surveyed for fuel levels, vegetational structures, and topographic characteristics. Most of the surveyed sites were on Los Alamos National Laboratory property, however, some surveys were also conducted on U.S. Forest Service property. The overall vegetation of these sites ranged from pinon-juniper woodlands to ponderosa pine forests to mixed conifer forests, and the topographic positions included canyons, mesas, and mountains. The results of these surveys indicate that the understory fuels are the greatest in mixed conifer forests and that overstory fuels are greatest in both mixed conifer forests and ponderosa pine forests on mesas. The geographic distribution of these fuels would suggest a most credible wildfire scenario for the Los Alamos region. Three major fires have occurred since 1954 and these fires behaved in a manner that is consistent with this scenario. The most credible wildfire scenario was also supported by the results of BEHAVE modeling that used the fuels inventory data as inputs. Output from the BEHAVE model suggested that catastrophic wildfires would continue to occur during any season with sufficiently dry, windy weather.

  13. Cleanup at Los Alamos National Laboratory - the challenges - 9493

    SciTech Connect

    Stiger, Susan G; Hargis, Kenneth M; Graham, Michael J; Rael, George J

    2008-01-01

    This paper provides an overview of environmental cleanup at the Los Alamos National Laboratory (LANL) and some of the unique aspects and challenges. Cleanup of the 65-year old Department of Energy Laboratory is being conducted under a RCRA Consent Order with the State of New Mexico. This agreement is one of the most recent cleanup agreements signed in the DOE complex and was based on lessons learned at other DOE sites. A number of attributes create unique challenges for LANL cleanup -- the proximity to the community and pueblos, the site's topography and geology, and the nature of LANL's on-going missions. This overview paper will set the stage for other papers in this session, including papers that present: Plans to retrieve buried waste at Material Disposal Area B, across the street from oen of Los Alamos' commercial districts and the local newspaper; Progress to date and joint plans with WIPP for disposal of the remaining inventory of legacy transuranic waste; Reviews of both groundwater and surface water contamination and the factors complicating both characterization and remediation; Optimizing the disposal of low-level radioactive waste from ongoing LANL missions; A stakeholder environmental data transparency project (RACER), with full public access to all available information on contamination at LANL, and A description of the approach to waste processing cost recovery from the programs that generate hazardous and radioactive waste at LANL.

  14. An organizational survey of the Los Alamos Site

    SciTech Connect

    Shurberg, D.A.; Haber, S.B.

    1991-11-01

    An Organizational Survey (OS) was administered at the Los Alamos Site that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concern, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of ``culture;`` that is, the values, attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization. While comparisons among groups are made, it is not the purpose of this report to make evaluative statements of which profile may be positive or negative. However, using the data presented in this report in conjunction with other evaluative activities, may provide useful insight into the organization. The OS administration at the Los Alamos Site was the ninth to occur at a Department of Energy (DOE) facility. All data from the OS is presented in group summaries, by organization, department or directorate within organization, supervisory level both overall and within organization, and staff classification within organization. Statistically significant differences between groups are identified and discussed. 9 refs., 94 figs., 11 tabs.

  15. An organizational survey of the Los Alamos Site

    SciTech Connect

    Shurberg, D.A.; Haber, S.B.

    1991-11-01

    An Organizational Survey (OS) was administered at the Los Alamos Site that queried employees on the subjects of organizational culture, various aspects of communications, employee commitment, work group cohesion, coordination of work, environmental, safety, and health concern, hazardous nature of work, safety and overall job satisfaction. The purpose of the OS is to measure in a quantitative and objective way the notion of culture;'' that is, the values, attitudes, and beliefs of the individuals working within the organization. In addition, through the OS, a broad sample of individuals can be reached that would probably not be interviewed or observed during the course of a typical assessment. The OS also provides a descriptive profile of the organization at one point in time that can then be compared to a profile taken at a different point in time to assess changes in the culture of the organization. While comparisons among groups are made, it is not the purpose of this report to make evaluative statements of which profile may be positive or negative. However, using the data presented in this report in conjunction with other evaluative activities, may provide useful insight into the organization. The OS administration at the Los Alamos Site was the ninth to occur at a Department of Energy (DOE) facility. All data from the OS is presented in group summaries, by organization, department or directorate within organization, supervisory level both overall and within organization, and staff classification within organization. Statistically significant differences between groups are identified and discussed. 9 refs., 94 figs., 11 tabs.

  16. Exploding metallic foil fuse modeling at Los Alamos

    SciTech Connect

    Lindemuth, I.R.; Reinovsky, R.E.; Goforth, J.H.

    1989-01-01

    A ''first-principles'' computational model of exploding metallic foil behavior has been developed at Los Alamos. The model couples zero-dimensional magnetohydrodynamics with ohmic heating and electrical circuit equations and uses the Los Alamos SESAME atomic data base computer library to determine the foil material's temperature- and density-dependent pressure, specific energy, and electrical conductivity. The model encompasses many previously successful empirical models and offers plausible physical explanations of phenomena not treated by the empirical models. In addition to addressing the electrical circuit performance of an exploding foil, the model provides information on the temporal evolution of the foil material's density, temperature, pressure, electrical conductivity, and expansion and translational velocities. In this paper, we report the physical insight gained by computational studies of two opening switch concepts being developed for application in an FCG-driven 1-MJ-class imploding plasma z-pinch experiment. The first concept considered is a ''conventional'' electrically exploded fuse, which has been demonstrated to operate at 16 MA driven by the 15-MJ-class FCG to be used in the 1 MJ implosion experiment. The second concept considered is a Type 2 explosively formed fuse (EFF), which has been demonstrated to operate at the 8 MA level by a 1-MJ-class FCG.

  17. Exploding metallic foil fuse modeling at Los Alamos

    NASA Astrophysics Data System (ADS)

    Lindemuth, Irvin R.; Reinovsky, Robert E.; Goforth, James H.

    A first-principles computational model of exploding metallic foil behavior was developed at Los Alamos. The model couples zero-dimensional magnetohydrodynamics with ohmic heating and electrical circuit equations and uses the Los Alamos SESAME atomic data base computer library to determine the foil material's temperature- and density-dependent pressure, specific energy, and electrical conductivity. The model encompasses many previously successful empirical models and offers plausible physical explanations of phenomena not treated by the empirical models. In addition to addressing the electrical circuit performance of an exploding foil, the model provides information on the temporal evolution of the foil material's density, temperature, pressure, electrical conductivity, and expansion and translational velocities. The physical insight gained by computational studies of two opening switch concepts being developed for application in an FCG-driven 1-MJ-class imploding plasma z-pinch experiment are reported. The first concept considered is a conventional electrically exploded fuse, which was demonstrated to operate at 16 MA driven by the 15-MJ-class FCG to be used in the 1 MJ implosion experiment. The second concept considered is a Type 2 explosively formed fuse (EFF), which was demonstrated to operate at the 8 MA level by a 1-MJ-class FCG.

  18. Water supply at Los Alamos during 1987: Progress report

    SciTech Connect

    Purtymun, W.D.; Stoker, A.K.; Maes, M.N.

    1989-01-01

    Municipal and industrial water supply during 1987 was 1594 /times/ 10W gal from wells in three fields and 34 /times/ 10W gal from the spring gallery in Water Canyon. About 2.8 /times/ 10W gal of nonpotable water from the Guaje Reservoir and 3.2 /times/ 10W gal from the Los Alamos Reservoir were used for irrigation; thus, the total water usage in 1987 was about 1634 /times/ 10W gal. Water supply was satisfactory in that the production met demand and water quality in the distribution system was in compliance with state and federal regulations. However, in 1987 two wells were lost because of deterioration of the casing and screen. In spite of rehabilitation attempts to maintain the yield, production from the older wells continued to decline. A comprehensive evaluation of the wells and well fields made in late 1987 concluded that replacement wells and new wells were needed soon to ensure a reliable water supply for the Laboratory and the county of Los Alamos. 25 refs., 6 figs., 7 tabs.

  19. Seismic vulnerability study Los Alamos Meson Physics Facility (LAMPF)

    SciTech Connect

    Salmon, M.; Goen, L.K.

    1995-12-01

    The Los Alamos Meson Physics Facility (LAMPF), located at TA-53 of Los Alamos National Laboratory (LANL), features an 800 MeV proton accelerator used for nuclear physics and materials science research. As part of the implementation of DOE Order 5480.25 and in preparation for DOE Order 5480.28, a seismic vulnerability study of the structures, systems, and components (SSCs) supporting the beam line from the accelerator building through to the ends of die various beam stops at LAMPF has been performed. The study was accomplished using the SQUG GIP methodology to assess the capability of the various SSCs to resist an evaluation basis earthquake. The evaluation basis earthquake was selected from site specific seismic hazard studies. The goals for the study were as follows: (1) identify SSCs which are vulnerable to seismic loads; and (2) ensure that those SSCs screened during die evaluation met the performance goals required for DOE Order 5480.28. The first goal was obtained by applying the SQUG GIP methodology to those SSCS represented in the experience data base. For those SSCs not represented in the data base, information was gathered and a significant amount of engineering judgment applied to determine whether to screen the SSC or to classify it as an outlier. To assure the performance goals required by DOE Order 5480.28 are met, modifications to the SQUG GIP methodology proposed by Salmon and Kennedy were used. The results of this study ire presented in this paper.

  20. Performance programming with the Los Alamos macro accelerator

    NASA Astrophysics Data System (ADS)

    Cort, G.

    The CCC macro facility, as extended by Version 2.0 of Softool's Change and Configuration Control Environment, offers many new and powerful features. Among these are a vastly extended suite of commands, error trapping, and structured constructs. In concert with previously existing Version 1.x features (notably the very powerful symbol substitution and parameter passage facilities), these features combine to transform the macro facility from a simple command language into an extremely flexible programming language which is suitable for developing very large and complex applications. This paper presents the results of a performance analysis of the CCC macro facility conducted at the Los Alamos National Laboratory Weapons Neutron Research Facility. The goal of this work was to identify and evaluate major factors that can contribute to the degradation of performance of the CCC macro facility, and to develop strategies for countering their effects. In particular, we report on the Los Alamos Macro Accelerator, which can produce dramatic increases in execution speed for many applications.

  1. Investigation of excess thyroid cancer incidence in Los Alamos County

    SciTech Connect

    Athas, W.F.

    1996-04-01

    Los Alamos County (LAC) is home to the Los Alamos National Laboratory, a U.S. Department of Energy (DOE) nuclear research and design facility. In 1991, the DOE funded the New Mexico Department of Health to conduct a review of cancer incidence rates in LAC in response to citizen concerns over what was perceived as a large excess of brain tumors and a possible relationship to radiological contaminants from the Laboratory. The study found no unusual or alarming pattern in the incidence of brain cancer, however, a fourfold excess of thyroid cancer was observed during the late-1980`s. A rapid review of the medical records for cases diagnosed between 1986 and 1990 failed to demonstrate that the thyroid cancer excess had resulted from enhanced detection. Surveillance activities subsequently undertaken to monitor the trend revealed that the excess persisted into 1993. A feasibility assessment of further studies was made, and ultimately, an investigation was conducted to document the epidemiologic characteristics of the excess in detail and to explore possible causes through a case-series records review. Findings from the investigation are the subject of this report.

  2. Mixed low-level waste minimization at Los Alamos

    SciTech Connect

    Starke, T.P.

    1998-12-01

    During the first six months of University of California 98 Fiscal Year (July--December) Los Alamos National Laboratory has achieved a 57% reduction in mixed low-level waste generation. This has been accomplished through a systems approach that identified and minimized the largest MLLW streams. These included surface-contaminated lead, lead-lined gloveboxes, printed circuit boards, and activated fluorescent lamps. Specific waste minimization projects have been initiated to address these streams. In addition, several chemical processing equipment upgrades are being implemented. Use of contaminated lead is planned for several high energy proton beam stop applications and stainless steel encapsulated lead is being evaluated for other radiological control area applications. INEEL is assisting Los Alamos with a complete systems analysis of analytical chemistry derived mixed wastes at the CMR building and with a minimum life-cycle cost standard glovebox design. Funding for waste minimization upgrades has come from several sources: generator programs, waste management, the generator set-aside program, and Defense Programs funding to INEEL.

  3. School Finance in a Federal City: Los Alamos as a Case Study.

    ERIC Educational Resources Information Center

    Smith, Duane W.

    The Los Alamos schools obtain support from a combination of local, state, and Department of Energy funds mandated by the Atomic Energy Commission Community Act. Each year the Los Alamos schools prepare three budgets, and during any week the schools may work directly with all three levels of government concerning funding. In 1974 the state of New…

  4. Recollections of a very junior physicist at Los Alamos, 1944-1946

    NASA Astrophysics Data System (ADS)

    French, Anthony P.

    2008-04-01

    The author came to Los Alamos as a member of the British Mission after two years of making fission cross section measurements at the Cavendish Laboratory. He worked in a group headed by Egon Bretscher in Enrico Fermi's F Division. The talk presents his personal memories and experiences at Los Alamos as compared to his life and work in wartime Britain.

  5. 1993 Annual PCB Document for Los Alamos National Laboratory EPA Region VI, January 1, 1993 through December 31, 1993

    SciTech Connect

    Wechsler, R.J.; Sandoval, T.M.; Bryant, D.E.; Hupke, L.; Esquibel, L.

    1995-12-31

    This document, the {open_quotes}1993 Annual PCB Document for Los Alamos National Laboratory{close_quotes} was prepared to fulffill the requirements of the federal PCB (Polychlorinated Biphenyl) regulation: 40 CFR 761 Subpart J General Records and Reports. The PCB Management Program at Los Alamos National Laboratory (LANL), Environmental Protection Group, compiled this 1993 Annual PCB Document. The overall format generally follows the sequence of the applicable regulations. Subsection 1.2 cross references those regulatory requirements with the applicable Document Section. The scope of this document also includes status summaries of various aspects of LANL`s PCB Management Program. The intent of this approach to the Annual Document is to provide an overview of LANL`s PCB Management Program and to increase the usefulness of this document as a management tool. Section 2.0, {open_quotes}Status of the PCB Management Program{close_quotes}, discusses the use, generation of waste, and storage of PCBs at LANL. Section 3.0 is the 1993 Annual Document Log required by 761.180(a). This Section also discusses the PCB Management Program`s policies for reporting under those regulatory requirements. Sections 4.0 and 5.0 contain the 1993 Annual Records for off-site and on-site disposal as required by 761.180(b). There is a tab for each manifest and its associated continuation sheets, receipt letters, and certificates of disposal.

  6. CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants

    PubMed Central

    Dommaraju, Kalpana; Kijak, Gustavo; Carlson, Jonathan M.; Larsen, Brendan B.; Tovanabutra, Sodsai; Geraghty, Dan E.; Deng, Wenjie; Maust, Brandon S.; Edlefsen, Paul T.; Sanders-Buell, Eric; Ratto-Kim, Silvia; deSouza, Mark S.; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttihum, Punnee; Kaewkungwal, Jaranit; O'Connell, Robert J.; Robb, Merlin L.; Michael, Nelson L.; Mullins, James I.; Kim, Jerome H.; Rolland, Morgane

    2014-01-01

    The modest protection afforded by the RV144 vaccine offers an opportunity to evaluate its mechanisms of protection. Differences between HIV-1 breakthrough viruses from vaccine and placebo recipients can be attributed to the RV144 vaccine as this was a randomized and double-blinded trial. CD8 and CD4 T cell epitope repertoires were predicted in HIV-1 proteomes from 110 RV144 participants. Predicted Gag epitope repertoires were smaller in vaccine than in placebo recipients (p = 0.019). After comparing participant-derived epitopes to corresponding epitopes in the RV144 vaccine, the proportion of epitopes that could be matched differed depending on the protein conservation (only 36% of epitopes in Env vs 84–91% in Gag/Pol/Nef for CD8 predicted epitopes) or on vaccine insert subtype (55% against CRF01_AE vs 7% against subtype B). To compare predicted epitopes to the vaccine, we analyzed predicted binding affinity and evolutionary distance measurements. Comparisons between the vaccine and placebo arm did not reveal robust evidence for a T cell driven sieve effect, although some differences were noted in Env-V2 (0.022≤p-value≤0.231). The paucity of CD8 T cell responses identified following RV144 vaccination, with no evidence for V2 specificity, considered together both with the association of decreased infection risk in RV 144 participants with V-specific antibody responses and a V2 sieve effect, lead us to hypothesize that this sieve effect was not T cell specific. Overall, our results did not reveal a strong differential impact of vaccine-induced T cell responses among breakthrough infections in RV144 participants. PMID:25350851

  7. Population-Level Immune-Mediated Adaptation in HIV-1 Polymerase during the North American Epidemic

    PubMed Central

    Kinloch, Natalie N.; MacMillan, Daniel R.; Le, Anh Q.; Cotton, Laura A.; Bangsberg, David R.; Buchbinder, Susan; Carrington, Mary; Fuchs, Jonathan; Harrigan, P. Richard; Koblin, Beryl; Kushel, Margot; Markowitz, Martin; Mayer, Kenneth; Milloy, M. J.; Schechter, Martin T.; Wagner, Theresa; Walker, Bruce D.; Carlson, Jonathan M.; Poon, Art F. Y.

    2015-01-01

    ABSTRACT Human leukocyte antigen (HLA) class I-associated polymorphisms in HIV-1 that persist upon transmission to HLA-mismatched hosts may spread in the population as the epidemic progresses. Transmission of HIV-1 sequences containing such adaptations may undermine cellular immune responses to the incoming virus in future hosts. Building upon previous work, we investigated the extent of HLA-associated polymorphism accumulation in HIV-1 polymerase (Pol) through comparative analysis of linked HIV-1/HLA class I genotypes sampled during historic (1979 to 1989; n = 338) and modern (2001 to 2011; n = 278) eras from across North America (Vancouver, BC, Canada; Boston, MA; New York, NY; and San Francisco, CA). Phylogenies inferred from historic and modern HIV-1 Pol sequences were star-like in shape, with an inferred most recent common ancestor (epidemic founder virus) sequence nearly identical to the modern North American subtype B consensus sequence. Nevertheless, modern HIV-1 Pol sequences exhibited roughly 2-fold-higher patristic (tip-to-tip) genetic distances than historic sequences, with HLA pressures likely driving ongoing diversification. Moreover, the frequencies of published HLA-associated polymorphisms in individuals lacking the selecting HLA class I allele was on average ∼2.5-fold higher in the modern than in the historic era, supporting their spread in circulation, though some remained stable in frequency during this time. Notably, polymorphisms restricted by protective HLA alleles appear to be spreading to a greater relative extent than others, though these increases are generally of modest absolute magnitude. However, despite evidence of polymorphism spread, North American hosts generally remain at relatively low risk of acquiring an HIV-1 polymerase sequence substantially preadapted to their HLA profiles, even in the present era. IMPORTANCE HLA class I-restricted cytotoxic T-lymphocyte (CTL) escape mutations in HIV-1 that persist upon transmission may

  8. BioAfrica's HIV-1 proteomics resource: combining protein data with bioinformatics tools.

    PubMed

    Doherty, Ryan S; De Oliveira, Tulio; Seebregts, Chris; Danaviah, Sivapragashini; Gordon, Michelle; Cassol, Sharon

    2005-01-01

    Most Internet online resources for investigating HIV biology contain either bioinformatics tools, protein information or sequence data. The objective of this study was to develop a comprehensive online proteomics resource that integrates bioinformatics with the latest information on HIV-1 protein structure, gene expression, post-transcriptional/post-translational modification, functional activity, and protein-macromolecule interactions. The BioAfrica HIV-1 Proteomics Resource http://bioafrica.mrc.ac.za/proteomics/index.html is a website that contains detailed information about the HIV-1 proteome and protease cleavage sites, as well as data-mining tools that can be used to manipulate and query protein sequence data, a BLAST tool for initiating structural analyses of HIV-1 proteins, and a proteomics tools directory. The Proteome section contains extensive data on each of 19 HIV-1 proteins, including their functional properties, a sample analysis of HIV-1HXB2, structural models and links to other online resources. The HIV-1 Protease Cleavage Sites section provides information on the position, subtype variation and genetic evolution of Gag, Gag-Pol and Nef cleavage sites. The HIV-1 Protein Data-mining Tool includes a set of 27 group M (subtypes A through K) reference sequences that can be used to assess the influence of genetic variation on immunological and functional domains of the protein. The BLAST Structure Tool identifies proteins with similar, experimentally determined topologies, and the Tools Directory provides a categorized list of websites and relevant software programs. This combined database and software repository is designed to facilitate the capture, retrieval and analysis of HIV-1 protein data, and to convert it into clinically useful information relating to the pathogenesis, transmission and therapeutic response of different HIV-1 variants. The HIV-1 Proteomics Resource is readily accessible through the BioAfrica website at: http

  9. Side Effects of HIV Medicines: HIV and Hepatotoxicity

    MedlinePlus

    Side Effects of HIV Medicines HIV and Hepatotoxicity (Last updated 1/7/2016; last reviewed 1/7/2016) Key Points Hepatotoxicity means damage to the ... the liver can be life-threatening. What HIV medicines can cause hepatotoxicity? HIV medicines in the following ...

  10. [HIV and reproductive choices].

    PubMed

    Boer, K; de Vries, J W; de Beaufort, I E

    1995-05-13

    It is estimated that there are about 120-150 hemophilic men infected with HIV in the Netherlands as well as 1000 men infected via intravenous drug use. The majority of them are in reproductive age with relationships with seronegative women. In the event they want to have a child, artificial insemination with donor sperm (KID) is an option. In 1994 there were 147 instances of insemination of 66 women with the processed semen of HIV-positive men and no infection resulted. The annual risk of HIV infection was 7.2% of a woman engaging in unprotected intercourse, according to a prospective Italian study. The risk of HIV infection per contact was estimated at 0.1-5.6%. However, it is not yet proven that processed sperm of an HIV-seropositive man can produce a pregnancy without the risk of infecting the woman. The risk of transmission of HIV to the fetus is higher in artificial insemination of a seropositive woman with the sperm of her partner. In vitro fertilization is not a sure method either for the prevention of HIV infection of the mother because of the possibility of an egg cell being infected before fertilization. HIV-infected pregnant women face the problems of caring for HIV-infected offspring. For HIV discordant couples the advice is to use both condoms for the prevention of infection and oral contraceptives for the prevention of pregnancy. In the case of a lesbian relationship, if the partners want to have a child, HIV infection is still a factor because of previous heterosexual contacts.

  11. Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

  12. HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers.

    PubMed

    Sanders, Rogier W; van Gils, Marit J; Derking, Ronald; Sok, Devin; Ketas, Thomas J; Burger, Judith A; Ozorowski, Gabriel; Cupo, Albert; Simonich, Cassandra; Goo, Leslie; Arendt, Heather; Kim, Helen J; Lee, Jeong Hyun; Pugach, Pavel; Williams, Melissa; Debnath, Gargi; Moldt, Brian; van Breemen, Mariëlle J; Isik, Gözde; Medina-Ramírez, Max; Back, Jaap Willem; Koff, Wayne C; Julien, Jean-Philippe; Rakasz, Eva G; Seaman, Michael S; Guttman, Miklos; Lee, Kelly K; Klasse, Per Johan; LaBranche, Celia; Schief, William R; Wilson, Ian A; Overbaugh, Julie; Burton, Dennis R; Ward, Andrew B; Montefiori, David C; Dean, Hansi; Moore, John P

    2015-07-10

    A challenge for HIV-1 immunogen design is the difficulty of inducing neutralizing antibodies (NAbs) against neutralization-resistant (tier 2) viruses that dominate human transmissions. We show that a soluble recombinant HIV-1 envelope glycoprotein trimer that adopts a native conformation, BG505 SOSIP.664, induced NAbs potently against the sequence-matched tier 2 virus in rabbits and similar but weaker responses in macaques. The trimer also consistently induced cross-reactive NAbs against more sensitive (tier 1) viruses. Tier 2 NAbs recognized conformational epitopes that differed between animals and in some cases overlapped with those recognized by broadly neutralizing antibodies (bNAbs), whereas tier 1 responses targeted linear V3 epitopes. A second trimer, B41 SOSIP.664, also induced a strong autologous tier 2 NAb response in rabbits. Thus, native-like trimers represent a promising starting point for the development of HIV-1 vaccines aimed at inducing bNAbs.

  13. Linear induction accelerators at the Los Alamos National Laboratory DARHT facility

    SciTech Connect

    Nath, Subrata

    2010-09-07

    The Dual-Axis Radiographic Hydrodynamic Test Facility (DARHT) at Los Alamos National Laboratory consists of two linear induction accelerators at right angles to each other. The First Axis, operating since 1999, produces a nominal 20-MeV, 2-kA single beam-pulse with 60-nsec width. In contrast, the DARHT Second Axis, operating since 2008, produces up to four pulses in a variable pulse format by slicing micro-pulses out of a longer {approx}1.6-microseconds (flat-top) pulse of nominal beam-energy and -current of 17 MeV and 2 kA respectively. Bremsstrahlung x-rays, shining on a hydro-dynamical experimental device, are produced by focusing the electron beam-pulses onto a high-Z target. Variable pulse-formats allow for adjustment of the pulse-to-pulse doses to record a time sequence of x-ray images of the explosively driven imploding mock device. Herein, we present a sampling of the numerous physics and engineering aspects along with the current status of the fully operational dual axes capability. First successful simultaneous use of both the axes for a hydrodynamic experiment was achieved in 2009.

  14. Uncertainty quantification and global sensitivity analysis of the Los Alamos sea ice model

    NASA Astrophysics Data System (ADS)

    Urrego-Blanco, Jorge R.; Urban, Nathan M.; Hunke, Elizabeth C.; Turner, Adrian K.; Jeffery, Nicole

    2016-04-01

    Changes in the high-latitude climate system have the potential to affect global climate through feedbacks with the atmosphere and connections with midlatitudes. Sea ice and climate models used to understand these changes have uncertainties that need to be characterized and quantified. We present a quantitative way to assess uncertainty in complex computer models, which is a new approach in the analysis of sea ice models. We characterize parametric uncertainty in the Los Alamos sea ice model (CICE) in a standalone configuration and quantify the sensitivity of sea ice area, extent, and volume with respect to uncertainty in 39 individual model parameters. Unlike common sensitivity analyses conducted in previous studies where parameters are varied one at a time, this study uses a global variance-based approach in which Sobol' sequences are used to efficiently sample the full 39-dimensional parameter space. We implement a fast emulator of the sea ice model whose predictions of sea ice extent, area, and volume are used to compute the Sobol' sensitivity indices of the 39 parameters. Main effects and interactions among the most influential parameters are also estimated by a nonparametric regression technique based on generalized additive models. A ranking based on the sensitivity indices indicates that model predictions are most sensitive to snow parameters such as snow conductivity and grain size, and the drainage of melt ponds. It is recommended that research be prioritized toward more accurately determining these most influential parameter values by observational studies or by improving parameterizations in the sea ice model.

  15. Multiple co-circulating HIV-1 subtypes in the Middle East and North Africa

    PubMed Central

    Rolland, Morgane; Modjarrad, Kayvon

    2015-01-01

    HIV-1 incidence has been increasing more rapidly in the Middle East and North Africa than in any other global region. Despite this trend, HIV epidemiology in the region remains poorly defined. We conducted an analysis of 3284 publicly available HIV-1 sequences from 15 countries in the Middle East and North Africa to better characterize the regional epidemic. A phylogenetic tree based on the reverse transcriptase gene revealed a complex mosaic of diverse HIV subtypes and circulating recombinant forms across the region. PMID:26091303

  16. Positive: HIV Affirmative Counseling.

    ERIC Educational Resources Information Center

    Kain, Craig D.

    At the end of the 1980s, counselors largely lacked an integrated approach to counseling people living with HIV disease. This book describes the experience of counseling this group of persons. The major premise here is that counselors who counsel HIV-positive clients must come to understand and affirm their clients' experiences. The text defines a…

  17. Psychoneuroimmunology and HIV-1.

    ERIC Educational Resources Information Center

    Antoni, Michael H.; And Others

    1990-01-01

    Presents evidence describing benefits of behavioral interventions such as aerobic exercise training on both psychological and immunological functioning among high risk human immunodeficiency virus-Type 1 (HIV-1) seronegative and very early stage seropositive homosexual men. HIV-1 infection is cast as chronic disease for which early…

  18. HIV and Communication

    ERIC Educational Resources Information Center

    McNeilly, L.G.

    2005-01-01

    The human immunodeficiency virus (HIV) continues to plague many countries across the globe, including the United States, Africa, China and India. Children and adults have been infected with HIV, and both populations can present with communication disorders that coexist with the presence of the virus. The purpose of this paper is to present an…

  19. Overview of HIV.

    PubMed

    Klimas, Nancy; Koneru, Anne O'Brien; Fletcher, Mary Ann

    2008-06-01

    This article provides an overview and reviews the HIV pandemic, the basic biology and immunology of the virus (e.g., genetic diversity of HIV and the viral life cycle), the phases of disease progression, modes of HIV transmission, HIV testing, immune response to the infection, and current therapeutic strategies. HIV is occurring in epidemic proportions, especially in Sub-Saharan Africa. In the US, men who have sex with men account for over half of AIDS diagnoses; racial and ethnic minorities are disproportionally affected. Factors influencing the progression and severity of HIV infection include type of immune response, coinfection (e.g., another sexually transmitted infection, including hepatitis B or C), age and behavioral and psychosocial factors. Antiretroviral therapies can achieve reduction in blood levels of the HIV virus below the limits of detection by current technology. However, effective treatment requires adherence to therapy. Patient failure to adhere to treatment regimens results in detectible circulating virus and in HIV disease progression, and is the primary cause of drug resistance. In addition to research on the immunology and virology of the disease, other studies focus on behavioral and psychosocial factors that may affect medication adherence and risk behaviors. PMID:18541903

  20. Women and HIV

    MedlinePlus

    ... The impact of HIV is especially great among young women of color. More than one third of new ... legs. Abnormal pre-cancerous cell types related to cervical cancer are more frequent and severe in women who are HIV-positive. See fact sheet 510 ...

  1. Living with HIV/AIDS

    MedlinePlus

    Infection with HIV is serious. But the outlook for people with HIV/AIDS is improving. If you are infected with HIV, there are many things you can do to ... health care provider who knows how to treat HIV. You may want to join a support group. ...

  2. Los Alamos Plutonium Facility implementation support project report

    SciTech Connect

    Thomas, C.C. Jr.; Ford, W.; Hsue, S.T.; Marshall, R.S.

    1982-05-01

    During FY 1981 the TA-55 Implementation Support Project provided assistance to the Los Alamos Plutonium Facility in materials accounting and control, including testing and evaluation of a solution mass measurement system, development and testing of a low-level plutonium assay system, holdup measurements, instrument design, and advice and consultation following the observation of semiannual inventories. This report describes the program envisioned for FY 1982, including demonstration of the solution mass measurement system and the associated calibration system, extension of the low-level plutonium assay system to solutions with americium/plutonium ratios of 10: to 20:1, and development and demonstration of a method to calibrate and routinely verify the plutonium oxalate assay instrument performance. The FY 1982 program is subject to changes based on TA-55 reevaluation of facility needs.

  3. Operational status of the Los Alamos neutron science center (LANSCE)

    SciTech Connect

    Jones, Kevin W; Erickson, John L; Schoenberg, Kurt F

    2010-01-01

    The Los Alamos Neutron Science Center (LANSCE) accelerator and beam delivery complex generates the proton beams that serve three neutron production sources; the thermal and cold source for the Manuel Lujan Jr. Neutron Scattering Center, the Weapons Neutron Research (WNR) high-energy neutron source, and a pulsed Ultra-Cold Neutron Source. These three sources are the foundation of strong and productive multi-disciplinary research programs that serve a diverse and robust user community. The facility also provides multiplexed beams for the production of medical radioisotopes and proton radiography of dynamic events. The recent operating history of these sources will be reviewed and plans for performance improvement will be discussed, together with the underlying drivers for the proposed LANSCE Refurbishment project. The details of this latter project are presented in a separate contribution.

  4. Los Alamos Explosives Performance Key to Stockpile Stewardship

    SciTech Connect

    Dattelbaum, Dana

    2014-11-03

    As the U.S. Nuclear Deterrent ages, one essential factor in making sure that the weapons will continue to perform as designed is understanding the fundamental properties of the high explosives that are part of a nuclear weapons system. As nuclear weapons go through life extension programs, some changes may be advantageous, particularly through the addition of what are known as "insensitive" high explosives that are much less likely to accidentally detonate than the already very safe "conventional" high explosives that are used in most weapons. At Los Alamos National Laboratory explosives research includes a wide variety of both large- and small-scale experiments that include small contained detonations, gas and powder gun firings, larger outdoor detonations, large-scale hydrodynamic tests, and at the Nevada Nuclear Security Site, underground sub-critical experiments.

  5. Recent progress of the Los Alamos advanced free electron laser

    SciTech Connect

    Nguyen, D.C.; Austin, R.H.; Chan, K.C.D.; Feldman, D.W.; Goldstein, J.C.; Gierman, S.M.; Kinross-Wright, J.M.; Kong, S.H.; Plato, J.G.; Russell, S.J.

    1994-05-01

    Many industrial and research applications can benefit from the availability of a compact, user-friendly, broadly tunable and high average power free electron laser (FEL). Over the past four years, the Los Alamos Advanced FEL has been built with these design goals. The key to a compact FEL is the integration of advanced beam technologies such as a high-brightness photoinjector, a high-gradient compact linac, and permanent magnet beamline components. These technologies enable the authors to shrink the FEL size yet maintain its high average power capability. The Advanced FEL has been in operation in the near ir (4-6 {mu}m) since early 1993. Recent results of the Advanced FEL lasing at saturation and upgrades to improve its average power are presented.

  6. Neutron Capture Experiments Using the DANCE Array at Los Alamos

    NASA Astrophysics Data System (ADS)

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Sleaford, B.; Wu, C. Y.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Krtička, M.; Bečvář, F.

    2009-03-01

    The Detector for Advanced Neutron Capture Experiments (DANCE) is designed for neutron capture measurements on very small and/or radioactive targets. The DANCE array of 160 BaF2 scintillation detectors is located at the Lujan Center at the Los Alamos Neutron Science Center (LANSCE). Accurate measurements of neutron capture data are important for many current applications as well as for basic understanding of neutron capture. The gamma rays following neutron capture reactions have been studied by the time-of-flight technique using the DANCE array. The high granularity of the array allows measurements of the gamma-ray multiplicity. The gamma-ray multiplicities and energy spectra for different multiplicities can be measured and analyzed for spin and parity determination of the resolved resonances.

  7. Tiger Team Assessment of the Los Alamos National Laboratory

    SciTech Connect

    Not Available

    1991-11-01

    The Management Subteam conducted a management and organization assessment of environment, safety, and health (ES H) activities performed by the Los Alamos National Laboratory (LANL) and onsite contractor personnel. The objectives of the assessment were to (1) evaluate the effectiveness of management systems and practices in terms of ensuring environmental compliance and the safety and health of workers and the general public, (2) identify key findings, and (3) identify root causes for all ES H findings and concerns. The scope of the assessment included examinations of the following from an ES H perspective: (1) strategic and program planning; (2) organizational structure and management configuration; (3) human resource management, including training and staffing; (4) management systems, including performance monitoring and assessment; (5) conduct of operations; (6) public and institutional interactions; and (7) corporate'' parent support.

  8. Los Alamos Discovers Super Efficient Solar Using Perovskite Crystals

    SciTech Connect

    Mohite, Aditya; Nie, Wanyi

    2015-01-29

    State-of-the-art photovoltaics using high-purity, large-area, wafer-scale single-crystalline semiconductors grown by sophisticated, high temperature crystal-growth processes offer promising routes for developing low-cost, solar-based clean global energy solutions for the future. Solar cells composed of the recently discovered material organic-inorganic perovskites offer the efficiency of silicon, yet suffer from a variety of deficiencies limiting the commercial viability of perovskite photovoltaic technology. In research to appear in Science, Los Alamos National Laboratory researchers reveal a new solution-based hot-casting technique that eliminates these limitations, one that allows for the growth of high-quality, large-area, millimeter-scale perovskite crystals and demonstrates that highly efficient and reproducible solar cells with reduced trap assisted recombination can be realized.

  9. The legacy and future of CFD at Los Alamos

    SciTech Connect

    Johnson, N.L.

    1996-06-01

    The early history is presented of the prolific development of CFD methods in the Fluid Dynamics Group (T-3) at Los Alamos National Laboratory in the years from 1958 to the late 1960`s. Many of the currently used numerical methods--PIC, MAC, vorticity-stream-function, ICE, ALE methods and the {kappa}-{var_epsilon} method for turbulence--originated during this time. The rest of the paper summarizes the current research in T-3 for CFD, turbulence and solids modeling. The research areas include reactive flows, multimaterial flows, multiphase flows and flows with spatial discontinuities. Also summarized are modern particle methods and techniques developed for large scale computing on massively parallel computing platforms and distributed processors.

  10. Environmental surveillance at Los Alamos during 1991. Environmental protection group

    SciTech Connect

    Dewart, J.; Kohen, K.L.

    1993-08-01

    This report describes the environmental surveillance program conducted by Los Alamos National Laboratory during 1991. Routine monitoring for radiation and for radioactive and chemical materials is conducted on the Laboratory site as well as in the surrounding region. Monitoring results are used to determine compliance with appropriate standards and to permit early identification of potentially undesirable trends. Results and interpretation of data for 1991 cover external penetrating radiation; quantities of airborne emissions and effluents; concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, municipal water supply, soils and sediments, and foodstuffs; and environmental compliance. Comparisons with appropriate standards, regulations, and background levels provide the basis for concluding that environmental effects from Laboratory operations are small and do not pose a threat to the public, Laboratory employees, or the environment.

  11. Root lengths of plants on Los Alamos National Laboratory lands

    SciTech Connect

    Tierney, G.D.; Foxx, T.S.

    1987-01-01

    Maximum root lengths of 22 plant species occurring on Los Alamos National Laboratory lands were measured. An average of two longest roots from each species were dug up and their lengths, typical shapes, and qualitative morphologics were noted along with the overstory dimensions of the plant individual with which the roots were associated. Maximum root lengths were compared with overstory (height times width) dimensions. Among the life forms studied, the shrubs tend to show the longest roots in relation to overstory size. Forbs show the shortest roots in relation to overstory size. Measurements of tree roots suggest only that immature trees on the Pajarito Plateau may have root-length to overstory-size ratios near one. 30 refs., 14 figs., 2 tabs.

  12. Misuse and intrusion detection at Los Alamos National Laboratory

    SciTech Connect

    Jackson, K.A.; Neuman, M.C.; Simmonds, D.D.; Stallings, C.A.; Thompson, J.L.; Christoph, G.G.

    1995-04-01

    An effective method for detecting computer misuse is the automatic auditing and analysis of on-line user activity. This activity is reflected in system audit records, in system vulnerability postures, and in other evidence found through active system testing. Since 1989 we have implemented a misuse and intrusion detection system at Los Alamos. This is the Network Anomaly Detection and Intrusion Reporter, or NADIR. NADIR currently audits a Kerberos distributed authentication system, file activity on a mass, storage system, and four Cray supercomputers that run the UNICOS operating system. NADIR summarizes user activity and system configuration in statistical profiles. It compares these profiles to expert rules that define security policy and improper or suspicious behavior. It reports suspicious behavior to security auditors and provides tools to aid in follow-up investigations, As NADIR is constantly evolving, this paper reports its development to date.

  13. Los Alamos Guns Take Aim at Material's Mysteries

    SciTech Connect

    Byers, Mark; Moore, David; Dimarino, Steve

    2014-04-14

    Los Alamos National Laboratory scientists and technicians conduct thousands of experiments a year, delving into the fundamental nature of everything from supernovas to subatomic particles. One set of instruments used to better understand the fundamental nature of various materials are 10 scientific gun systems that fire various projectiles at high-tech targets to create enormous velocities, pressures, and temperatures - and using laser, x-ray, and other diagnostics - explore the very nature of metals and other materials. The hundreds of gun-based experiments conducted every year at the Laboratory require a highly-skilled staff of scientists and technicians, and has given rise to a special organization called the "gun working group" to foster open communications, cooperation, problem-solving, and a healthy safety culture.

  14. Los Alamos Neutron Science Center (LANSCE) Nuclear Science Facilities

    SciTech Connect

    Nelson, Ronald Owen; Wender, Steve

    2015-06-19

    The Los Alamos Neutron Science Center (LANSCE) facilities for Nuclear Science consist of a high-energy "white" neutron source (Target 4) with 6 flight paths, three low-energy nuclear science flight paths at the Lujan Center, and a proton reaction area. The neutron beams produced at the Target 4 complement those produced at the Lujan Center because they are of much higher energy and have shorter pulse widths. The neutron sources are driven by the 800-MeV proton beam of the LANSCE linear accelerator. With these facilities, LANSCE is able to deliver neutrons with energies ranging from a milli-electron volt to several hundreds of MeV, as well as proton beams with a wide range of energy, time and intensity characteristics. The facilities, instruments and research programs are described briefly.

  15. The Los ALamos Neutron Science Center Hydrogen Moderator System

    NASA Astrophysics Data System (ADS)

    Jarmer, J. J.; Knudson, J. N.

    2006-04-01

    At the Los Alamos Neutron Science Center (LANSCE), spallation neutrons are produced by an 800-MeV proton beam interacting with tungsten targets. Gun-barrel-type penetrations through the heavy concrete and steel shielding that surround the targets collimate neutrons to form neutron beams used for scattering experiments. Two liquid hydrogen moderators of one-liter volume each are positioned adjacent to the neutron-production targets. Some of the neutrons that pass through a moderator interact with or scatter from protons in the hydrogen. The neutron-proton interaction reduces the energy or moderates neutrons to lower energies. Lower energy "moderated" neutrons are the most useful for some neutron scattering experiments. We provide a description of the LANSCE hydrogen-moderator system and its cryogenic performance with proton beams of up to 125 micro-amp average current.

  16. Los Alamos Explosives Performance Key to Stockpile Stewardship

    ScienceCinema

    Dattelbaum, Dana

    2016-07-12

    As the U.S. Nuclear Deterrent ages, one essential factor in making sure that the weapons will continue to perform as designed is understanding the fundamental properties of the high explosives that are part of a nuclear weapons system. As nuclear weapons go through life extension programs, some changes may be advantageous, particularly through the addition of what are known as "insensitive" high explosives that are much less likely to accidentally detonate than the already very safe "conventional" high explosives that are used in most weapons. At Los Alamos National Laboratory explosives research includes a wide variety of both large- and small-scale experiments that include small contained detonations, gas and powder gun firings, larger outdoor detonations, large-scale hydrodynamic tests, and at the Nevada Nuclear Security Site, underground sub-critical experiments.

  17. Neutron Capture Experiments Using the DANCE Array at Los Alamos

    SciTech Connect

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Sleaford, B.; Wu, C. Y.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Krticka, M.; Becvar, F.

    2009-03-31

    The Detector for Advanced Neutron Capture Experiments (DANCE) is designed for neutron capture measurements on very small and/or radioactive targets. The DANCE array of 160 BaF{sub 2} scintillation detectors is located at the Lujan Center at the Los Alamos Neutron Science Center (LANSCE). Accurate measurements of neutron capture data are important for many current applications as well as for basic understanding of neutron capture. The gamma rays following neutron capture reactions have been studied by the time-of-flight technique using the DANCE array. The high granularity of the array allows measurements of the gamma-ray multiplicity. The gamma-ray multiplicities and energy spectra for different multiplicities can be measured and analyzed for spin and parity determination of the resolved resonances.

  18. Smoking patterns among Los Alamos National Laboratory employees

    SciTech Connect

    Mahoney, M.C.; Wilkinson, G.S.

    1987-06-01

    Smoking patterns among 5507 employees at Los Alamos National Laboratory were investigated for those who underwent physical examinations by occupational physicians from 1978 to 1983. More male than female employees smoked, although differences in smoking rates between the sexes were not as large as differences observed for national smoking rates. Employees over 40 were more likely to smoke than younger employees, males consumed more cigarettes than did females, and Anglo employees smoked more cigarettes than did Hispanic employees. Highly educated employees smoked less than did less-educated workers, and staff members exhibited the lowest rates of smoking. Smoking cessation programs for Laboratory employees should be directed toward those subpopulations with the highest rates of smoking. 31 refs., 8 figs., 1 tab.

  19. Plans for an Ultra Cold Neutron source at Los Alamos

    SciTech Connect

    Seestrom, S.J.; Bowles, T.J.; Hill, R.; Greene, G.L.

    1996-10-01

    Ultra Cold Neutrons (UCN) can be produced at spallation sources using a variety of techniques. To date the technique used has been to Bragg scatter and Doppler shift cold neutrons into UCN from a moving crystal. This is particularly applicable to short-pulse spallation sources. We are presently constructing a UCN source at LANSCE using this method. In addition, large gains in UCN density should be possible using cryogenic UCN sources. Research is under way at Gatchina to demonstrate technical feasibility of a frozen deuterium source. If successful, a source of this type could be implemented at future spallation source, such as the long pulse source being planned at Los Alamos, with a UCN density that may be two orders of magnitude higher than that presently available at reactors.

  20. Los Alamos National Laboratory Develops ''Quick to WIPP'' Strategy

    SciTech Connect

    Jones, R.; Allen, G.; Kosiewicz, S.; Martin, B,; LANL; Nunz, J.; Biedscheid, J.; Sellmer, T.; Willis, J.; Orban, J.; Liekhus, K.; Djordjevic, S.

    2003-02-25

    The Cerro Grande forest fire in May of 2000 and the terrorist events of September 11, 2001 precipitated concerns of the vulnerability of legacy contact-handled (CH), high-wattage transuranic (TRU) waste stored at Los Alamos National Laboratory (LANL). An analysis of the 9,100 cubic meters of stored CH-TRU waste revealed that 400 cubic meters or 4.5% of the inventory represented 61% of the risk. The analysis further showed that this 400 cubic meters was contained in only 2,000 drums. These facts and the question ''How can the disposition of this waste to the Waste Isolation Pilot Plant (WIPP) be accelerated?'' formed the genesis of LANL's Quick to WIPP initiative.

  1. Los Alamos National Laboratory support to IAEA environmental safeguards

    SciTech Connect

    Steiner, Robert E; Dry, Don E; Roensch, Fred R; Kinman, Will S; Roach, Jeff L; La Mont, Stephen P

    2010-12-01

    The nuclear and radiochemistry group provides sample preparation and analysis support to the International Atomic Energy Agency (IAEA) Network of Analytical Laboratories (NWAL). These analyses include both non-destructive (alpha and gamma-ray spectrometry) and destructive (thermal ionization mass spectrometry and inductively coupled plasma mass spectrometry) methods. On a bi-annual basis the NWAL laboratories are invited to meet to discuss program evolution and issues. During this meeting each participating laboratory summarizes their efforts over the previous two years. This presentation will present Los Alamos National Laboratories efforts in support of this program. Data showing results from sample and blank analysis will be presented along with capability enhancement and issues that arose over the previous two years.

  2. Los Alamos National Laboratory capability reviews - FY 2011 status

    SciTech Connect

    Springer, Everett P

    2011-01-12

    Capability reviews are the Los Alamos National Laboratory approach to assess the quality of its science, technology, and engineering (STE), and its integration across the Laboratory. There are seven capability reviews in FY 2011 reviews. The Weapons Science and Engineering review will be replaced by the National Nuclear Security Administration's Predictive Science Panel for 2011 . Beginning in 2011, third-year LORD projects will be reviewed by capability review committees rather than the first-year LORD projects that have been performed for the last three years. This change addresses concerns from committees about reviewing a project before it had made any substantive progress. The current schedule, and chairs for the 2011 capability reviews is presented. The three-year cycle (2011-2013) for capability reviews are presented for planning purposes.

  3. Decommissioning the UHTREX Reactor Facility at Los Alamos, New Mexico

    SciTech Connect

    Salazar, M.; Elder, J.

    1992-08-01

    The Ultra-High Temperature Reactor Experiment (UHTREX) facility was constructed in the late 1960s to advance high-temperature and gas-cooled reactor technology. The 3-MW reactor was graphite moderated and helium cooled and used 93% enriched uranium as its fuel. The reactor was run for approximately one year and was shut down in February 1970. The decommissioning of the facility involved removing the reactor and its associated components. This document details planning for the decommissioning operations which included characterizing the facility, estimating the costs of decommissioning, preparing environmental documentation, establishing a system to track costs and work progress, and preplanning to correct health and safety concerns in the facility. Work to decommission the facility began in 1988 and was completed in September 1990 at a cost of $2.9 million. The facility was released to Department of Energy for other uses in its Los Alamos program.

  4. Environmental surveillance and compliance at Los Alamos during 1996

    SciTech Connect

    1997-09-01

    This report presents environmental data that characterize environmental performance and addresses compliance with environmental standards and requirements at Los Alamos National Laboratory (LANL or the Laboratory) during 1996. The Laboratory routinely monitors for radiation and for radioactive nonradioactive materials at Laboratory sites as well as in the surrounding region. LANL uses the monitoring results to determine compliance with appropriate standards and to identify potentially undesirable trends. Data were collected in 1996 to assess external penetrating radiation; quantities of airborne emissions; and concentrations of chemicals and radionuclides in ambient air, surface waters and groundwaters, the municipal water supply, soils and sediments, and foodstuffs. Using comparisons with standards and regulations, this report concludes that environmental effects from Laboratory operations are small and do not pose a demonstrable threat to the public, Laboratory employees, or the environment. Laboratory operations were in compliance with all major environmental regulations.

  5. Common ground: An environmental ethic for Los Alamos National Laboratory

    SciTech Connect

    Menlove, F.L.

    1991-01-01

    Three predominant philosophies have characterized American business ethical thinking over the past several decades. The first phase is the ethics of self-interest'' which argues that maximizing self-interest coincidentally maximizes the common good. The second phase is legality ethics.'' Proponents argue that what is important is knowing the rules and following them scrupulously. The third phase might be called stake-holder ethics.'' A central tenant is that everyone affected by a decision has a moral hold on the decision maker. This paper will discuss one recent initiative of the Los Alamos National Laboratory to move beyond rules and regulations toward an environmental ethic that integrates the values of stakeholder ethics'' into the Laboratory's historical culture and value systems. These Common Ground Principles are described. 11 refs.

  6. Los Alamos Guns Take Aim at Material's Mysteries

    ScienceCinema

    Byers, Mark; Moore, David; Dimarino, Steve

    2016-07-12

    Los Alamos National Laboratory scientists and technicians conduct thousands of experiments a year, delving into the fundamental nature of everything from supernovas to subatomic particles. One set of instruments used to better understand the fundamental nature of various materials are 10 scientific gun systems that fire various projectiles at high-tech targets to create enormous velocities, pressures, and temperatures - and using laser, x-ray, and other diagnostics - explore the very nature of metals and other materials. The hundreds of gun-based experiments conducted every year at the Laboratory require a highly-skilled staff of scientists and technicians, and has given rise to a special organization called the "gun working group" to foster open communications, cooperation, problem-solving, and a healthy safety culture.

  7. Los Alamos National Laboratory TRU waste sampling projects

    SciTech Connect

    Yeamans, D.; Rogers, P.; Mroz, E.

    1997-02-01

    The Los Alamos National Laboratory (LANL) has begun characterizing transuranic (TRU) waste in order to comply with New Mexico regulations, and to prepare the waste for shipment and disposal at the Waste Isolation Pilot Plant (WIPP), near Carlsbad, New Mexico. Sampling consists of removing some head space gas from each drum, removing a core from a few drums of each homogeneous waste stream, and visually characterizing a few drums from each heterogeneous waste stream. The gases are analyzed by GC/MS, and the cores are analyzed for VOC`s and SVOC`s by GC/MS and for metals by AA or AE spectroscopy. The sampling and examination projects are conducted in accordance with the ``DOE TRU Waste Quality Assurance Program Plan`` (QAPP) and the ``LANL TRU Waste Quality Assurance Project Plan,`` (QAPjP), guaranteeing that the data meet the needs of both the Carlsbad Area Office (CAO) of DOE and the ``WIPP Waste Acceptance Criteria, Rev. 5,`` (WAC).

  8. Cutaneous Leishmaniasis with HIV.

    PubMed

    Talat, Humaira; Attarwala, Sharmeen; Saleem, Mubasshir

    2014-05-01

    Cutaneous Leishmaniasis (CL) is a vector borne disease caused by various species of the Leishmania parasite. CL is endemic in the province of Balochistan in Pakistan. In certain instances a Human Immunodeficiency Virus (HIV)-related immunocompromised is associated with atypical clinical presentation and occurrence of reactivated lesions of CL. Such presentations respond poorly to the standard treatment and frequent relapses are noted. We are reporting three cases of localized and disseminated CL due to Leishmania tropica which responded to meglumine antimoniate. Due to the fact that CL is endemic in Balochistan, we did not consider HIV infection as a causative organism. It was their presentation with history of weight loss and fever that prompted Enzyme-linked Immunosorbent Assay (ELISA) tests for HIV, which turned out to be positive. CL is becoming visible as an opportunistic infection associated with HIV/AIDS and may even be the first symptom in HIV positive patients in an endemic area.

  9. Identification of potent maturation inhibitors against HIV-1 clade C

    PubMed Central

    Timilsina, Uddhav; Ghimire, Dibya; Timalsina, Bivek; Nitz, Theodore J.; Wild, Carl T.; Freed, Eric O.; Gaur, Ritu

    2016-01-01

    Antiretroviral therapy has led to a profound improvement in the clinical care of HIV-infected patients. However, drug tolerability and the evolution of drug resistance have limited treatment options for many patients. Maturation inhibitors are a new class of antiretroviral agents for treatment of HIV-1. They act by interfering with the maturation of the virus by blocking the last step in Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA by the viral protease (PR). The first-in-class maturation inhibitor bevirimat (BVM) failed against a subset of HIV-1 isolates in clinical trials due to polymorphisms present in the CA-SP1 region of the Gag protein. Sequence analysis indicated that these polymorphisms are more common in non-clade B strains of HIV-1 such as HIV-1 clade C. Indeed, BVM was found to be ineffective against HIV-1 clade C molecular clones tested in this study. A number of BVM analogs were synthesized by chemical modifications at the C-28 position to improve its activity. The new BVM analogs displayed potent activity against HIV-1 clade B and C and also reduced infectivity of the virus. This study identifies novel and broadly active BVM analogs that may ultimately demonstrate efficacy in the clinic. PMID:27264714

  10. Defining the roles for Vpr in HIV-1-associated neuropathogenesis.

    PubMed

    James, Tony; Nonnemacher, Michael R; Wigdahl, Brian; Krebs, Fred C

    2016-08-01

    It is increasingly evident that the human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) has a unique role in neuropathogenesis. Its ability to induce G2/M arrest coupled with its capacity to increase viral gene transcription gives it a unique role in sustaining viral replication and aiding in the establishment and maintenance of a systemic infection. The requirement of Vpr for HIV-1 infection and replication in cells of monocytic origin (a key lineage of cells involved in HIV-1 neuroinvasion) suggests an important role in establishing and sustaining infection in the central nervous system (CNS). Contributions of Vpr to neuropathogenesis can be expanded further through (i) naturally occurring HIV-1 sequence variation that results in functionally divergent Vpr variants; (ii) the dual activities of Vpr as a intracellular protein delivered and expressed during HIV-1 infection and as an extracellular protein that can act on neighboring, uninfected cells; (iii) cell type-dependent consequences of Vpr expression and exposure, including cell cycle arrest, metabolic dysregulation, and cytotoxicity; and (iv) the effects of Vpr on exosome-based intercellular communication in the CNS. Revealing that the effects of this pleiotropic viral protein is an essential part of a greater understanding of HIV-1-associated pathogenesis and potential approaches to treating and preventing disease caused by HIV-1 infection.

  11. Defining the roles for Vpr in HIV-1-associated neuropathogenesis.

    PubMed

    James, Tony; Nonnemacher, Michael R; Wigdahl, Brian; Krebs, Fred C

    2016-08-01

    It is increasingly evident that the human immunodeficiency virus type 1 (HIV-1) viral protein R (Vpr) has a unique role in neuropathogenesis. Its ability to induce G2/M arrest coupled with its capacity to increase viral gene transcription gives it a unique role in sustaining viral replication and aiding in the establishment and maintenance of a systemic infection. The requirement of Vpr for HIV-1 infection and replication in cells of monocytic origin (a key lineage of cells involved in HIV-1 neuroinvasion) suggests an important role in establishing and sustaining infection in the central nervous system (CNS). Contributions of Vpr to neuropathogenesis can be expanded further through (i) naturally occurring HIV-1 sequence variation that results in functionally divergent Vpr variants; (ii) the dual activities of Vpr as a intracellular protein delivered and expressed during HIV-1 infection and as an extracellular protein that can act on neighboring, uninfected cells; (iii) cell type-dependent consequences of Vpr expression and exposure, including cell cycle arrest, metabolic dysregulation, and cytotoxicity; and (iv) the effects of Vpr on exosome-based intercellular communication in the CNS. Revealing that the effects of this pleiotropic viral protein is an essential part of a greater understanding of HIV-1-associated pathogenesis and potential approaches to treating and preventing disease caused by HIV-1 infection. PMID:27056720

  12. HIV Vaccination, is Breakthrough Underway?

    PubMed

    Lu, Da-Yong; Wu, Hong-Ying; Lu, Ting-Ren; Xu, Bin; Ding, Jian

    2016-01-01

    After long defeats-almost no marked breakthrough in HIV vaccination campaign has been observed during the past two decades, and we still have not lost our faiths for the development of highly effective and low risk HIV vaccines. Many effective vaccines have been discovered and will certainly enter into the markets within the next 5 to 10 years. In order to promote HIV vaccine developments and clinical HIV therapeutic improvements, this perspective addresses the good and bad sides of currently available HIV vaccines, discusses many subjects of medical significance and finally provides up-to-date information in the field of HIV studies, in particular regarding vaccine developments and HIV pathogenesis.

  13. 2013 Los Alamos National Laboratory Hazardous Waste Minimization Report

    SciTech Connect

    Salzman, Sonja L.; English, Charles J.

    2015-08-24

    Waste minimization and pollution prevention are inherent goals within the operating procedures of Los Alamos National Security, LLC (LANS). The US Department of Energy (DOE) and LANS are required to submit an annual hazardous waste minimization report to the New Mexico Environment Department (NMED) in accordance with the Los Alamos National Laboratory (LANL or the Laboratory) Hazardous Waste Facility Permit. The report was prepared pursuant to the requirements of Section 2.9 of the LANL Hazardous Waste Facility Permit. This report describes the hazardous waste minimization program (a component of the overall Waste Minimization/Pollution Prevention [WMin/PP] Program) administered by the Environmental Stewardship Group (ENV-ES). This report also supports the waste minimization and pollution prevention goals of the Environmental Programs Directorate (EP) organizations that are responsible for implementing remediation activities and describes its programs to incorporate waste reduction practices into remediation activities and procedures. LANS was very successful in fiscal year (FY) 2013 (October 1-September 30) in WMin/PP efforts. Staff funded four projects specifically related to reduction of waste with hazardous constituents, and LANS won four national awards for pollution prevention efforts from the National Nuclear Security Administration (NNSA). In FY13, there was no hazardous, mixedtransuranic (MTRU), or mixed low-level (MLLW) remediation waste generated at the Laboratory. More hazardous waste, MTRU waste, and MLLW was generated in FY13 than in FY12, and the majority of the increase was related to MTRU processing or lab cleanouts. These accomplishments and analysis of the waste streams are discussed in much more detail within this report.

  14. SNM holdup assessment of Los Alamos exhaust ducts. Final report

    SciTech Connect

    Marshall, R.S.

    1994-02-01

    Fissile material holdup in glovebox and fume hood exhaust ducting has been quantified for all Los Alamos duct systems. Gamma-based, nondestructive measurements were used to quantify holdup. The measurements were performed during three measurement campaigns. The first campaign, Phase I, provided foot-by-foot, semiquantitative measurement data on all ducting. These data were used to identify ducting that required more accurate (quantitative) measurement. Of the 280 duct systems receiving Phase I measurements, 262 indicated less than 50 g of fissile holdup and 19 indicated fissile holdup of 50 or more grams. Seven duct systems were measured in a second campaign, called Series 1, Phase II. Holdup estimates on these ducts ranged from 421 g of {sup 235}U in a duct servicing a shut-down uranium-machining facility to 39 g of {sup 239}Pu in a duct servicing an active plutonium-processing facility. Measurements performed in the second campaign proved excessively laborious, so a third campaign was initiated that used more efficient instrumentation at some sacrifice in measurement quality. Holdup estimates for the 12 duct systems measured during this third campaign ranged from 70 g of {sup 235}U in a duct servicing analytical laboratories to 1 g of {sup 235}U and 1 g of {sup 239}Pu in a duct carrying exhaust air to a remote filter building. These quantitative holdup estimates support the conclusion made at the completion of the Phase I measurements that only ducts servicing shut-down uranium operations contain about 400 g of fissile holdup. No ventilation ducts at Los Alamos contain sufficient fissile material holdup to present a criticality safety concern.

  15. Pinon Pine Tree Study, Los Alamos National Laboratory: Source document

    SciTech Connect

    P. R. Fresquez; J. D. Huchton; M. A. Mullen; L. Naranjo, Jr.

    2000-01-01

    One of the dominant tree species growing within and around Los Alamos National Laboratory (LANL), Los Alamos, NM, lands is the pinon pine (Pinus edulis) tree. Pinon pine is used for firewood, fence posts, and building materials and is a source of nuts for food--the seeds are consumed by a wide variety of animals and are also gathered by people in the area and eaten raw or roasted. This study investigated the (1) concentration of {sup 3}H, {sup 137}Cs, {sup 90}Sr, {sup tot}U, {sup 238}Pu, {sup 239,240}Pu, and {sup 241}Am in soils (0- to 12-in. [31 cm] depth underneath the tree), pinon pine shoots (PPS), and pinon pine nuts (PPN) collected from LANL lands and regional background (BG) locations, (2) concentrations of radionuclides in PPN collected in 1977 to present data, (3) committed effective dose equivalent (CEDE) from the ingestion of nuts, and (4) soil to PPS to PPN concentration ratios (CRs). Most radionuclides, with the exception of {sup 3}H in soils, were not significantly higher (p < 0.10) in soils, PPS, and PPN collected from LANL as compared to BG locations, and concentrations of most radionuclides in PPN from LANL have decreased over time. The maximum net CEDE (the CEDE plus two sigma minus BG) at the most conservative ingestion rate (10 lb [4.5 kg]) was 0.0018 mrem (0.018 {micro}Sv). Soil-to-nut CRs for most radionuclides were within the range of default values in the literature for common fruits and vegetables.

  16. Post-Cold War Science and Technology at Los Alamos

    NASA Astrophysics Data System (ADS)

    Browne, John C.

    2002-04-01

    Los Alamos National Laboratory serves the nation through the development and application of leading-edge science and technology in support of national security. Our mission supports national security by: ensuring the safety, security, and reliability of the U.S. nuclear stockpile; reducing the threat of weapons of mass destruction in support of counter terrorism and homeland defense; and solving national energy, environment, infrastructure, and health security problems. We require crosscutting fundamental and advanced science and technology research to accomplish our mission. The Stockpile Stewardship Program develops and applies, advanced experimental science, computational simulation, and technology to ensure the safety and reliability of U.S. nuclear weapons in the absence of nuclear testing. This effort in itself is a grand challenge. However, the terrorist attack of September 11, 2001, reminded us of the importance of robust and vibrant research and development capabilities to meet new and evolving threats to our national security. Today through rapid prototyping we are applying new, innovative, science and technology for homeland defense, to address the threats of nuclear, chemical, and biological weapons globally. Synergistically, with the capabilities that we require for our core mission, we contribute in many other areas of scientific endeavor. For example, our Laboratory has been part of the NASA effort on mapping water on the moon and NSF/DOE projects studying high-energy astrophysical phenomena, understanding fundamental scaling phenomena of life, exploring high-temperature superconductors, investigating quantum information systems, applying neutrons to condensed-matter and nuclear physics research, developing large-scale modeling and simulations to understand complex phenomena, and exploring nanoscience that bridges the atomic to macroscopic scales. In this presentation, I will highlight some of these post-cold war science and technology advances

  17. Four Amino Acid Changes in HIV-2 Protease Confer Class-Wide Sensitivity to Protease Inhibitors

    PubMed Central

    Smith, Robert A.; Gottlieb, Geoffrey S.

    2015-01-01

    ABSTRACT Protease is essential for retroviral replication, and protease inhibitors (PI) are important for treating HIV infection. HIV-2 exhibits intrinsic resistance to most FDA-approved HIV-1 PI, retaining clinically useful susceptibility only to lopinavir, darunavir, and saquinavir. The mechanisms for this resistance are unclear; although HIV-1 and HIV-2 proteases share just 38 to 49% sequence identity, all critical structural features of proteases are conserved. Structural studies have implicated four amino acids in the ligand-binding pocket (positions 32, 47, 76, and 82). We constructed HIV-2ROD9 molecular clones encoding the corresponding wild-type HIV-1 amino acids (I32V, V47I, M76L, and I82V) either individually or together (clone PRΔ4) and compared the phenotypic sensitivities (50% effective concentration [EC50]) of mutant and wild-type viruses to nine FDA-approved PI. Single amino acid replacements I32V, V47I, and M76L increased the susceptibility of HIV-2 to multiple PI, but no single change conferred class-wide sensitivity. In contrast, clone PRΔ4 showed PI susceptibility equivalent to or greater than that of HIV-1 for all PI. We also compared crystallographic structures of wild-type HIV-1 and HIV-2 proteases complexed with amprenavir and darunavir to models of the PRΔ4 enzyme. These models suggest that the amprenavir sensitivity of PRΔ4 is attributable to stabilizing enzyme-inhibitor interactions in the P2 and P2′ pockets of the protease dimer. Together, our results show that the combination of four amino acid changes in HIV-2 protease confer a pattern of PI susceptibility comparable to that of HIV-1, providing a structural rationale for intrinsic HIV-2 PI resistance and resolving long-standing questions regarding the determinants of differential PI susceptibility in HIV-1 and HIV-2. IMPORTANCE Proteases are essential for retroviral replication, and HIV-1 and HIV-2 proteases share a great deal of structural similarity. However, only three of nine

  18. Environmental Assessment for Electrical Power System Upgrades at Los Alamos National Laboratory, Los Alamos, New Mexico - Final Document

    SciTech Connect

    N /A

    2000-03-09

    The ''National Environmental Policy Act of 1969'' (NEPA) requires Federal agency officials to consider the environmental consequences of their proposed actions before decisions are made. In complying with NEPA, the United States (U.S.) Department of Energy (DOE) follows the Council on Environmental Quality (CEQ) regulations (40 Code of Federal Regulations [CFR] 1500-1508) and DOE's NEPA implementing procedures (10 CFR 1021). The purpose of an Environmental Assessment (EA) is to provide Federal decision makers with sufficient evidence and analysis to determine whether to prepare an Environmental Impact Statement (EIS) or issue a Finding of No Significant Impact. In this case, the DOE decision to be made is whether to construct and operate a 19.5-mile (mi) (31-kilometer [km]) electric transmission line (power line) reaching from the Norton Substation, west across the Rio Grande, to locations within the Los Alamos National Laboratory (LANL) Technical Areas (TAs) 3 and 5 at Los Alamos, New Mexico. The construction of one electric substation at LANL would be included in the project as would the construction of two line segments less than 1,200 feet (ft) (366 meters [m]) long that would allow for the uncrossing of a portion of two existing power lines. Additionally, a fiber optics communications line would be included and installed concurrently as part of the required overhead ground conductor for the power line. The new power line would improve the reliability of electric service in the LANL and Los Aktrnos County areas as would the uncrossing of the crossed segments of the existing lines. Additionally, installation of the new power line would enable the LANL and the Los Alamos County electric grid, which is a shared resource, to be adapted to accommodate the future import of increased power when additional power service becomes available in the northern New Mexico area. Similarly, the fiber optics line would allow DOE to take advantage of future opportunities in

  19. The Genetic Diversity and Evolution of HIV-1 Subtype B Epidemic in Puerto Rico

    PubMed Central

    López, Pablo; Rivera-Amill, Vanessa; Rodríguez, Nayra; Vargas, Freddie; Yamamura, Yasuhiro

    2015-01-01

    HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B). However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945) were obtained from our “HIV Genotyping” test file, which has been generated over a period of 14 years (2001–2014). REGA subtyping tool found the following subtypes: B (90%), B-like (3%), B/D recombinant (6%), and D/B recombinant (0.6%). Though there were fewer cases, the following subtypes were also found (in the given proportions): A1B (0.3%), BF1 (0.2%), subtype A (01-AE) (0.1%), subtype A (A2) (0.1%), subtype F (12BF) (0.1%), CRF-39 BF-like (0.1%), and others (0.1%). Some of the recombinants were identified as early as 2001. Although the HIV epidemic in Puerto Rico is primarily associated with HIV-1B virus, our analysis uncovered the presence of other subtypes. There was no indication of subtype C, which has been predominantly associated with heterosexual transmission in other parts of the world. PMID:26703695

  20. HIV-1 Evolutionary Patterns Associated with Metastatic Kaposi's Sarcoma during AIDS

    PubMed Central

    Lamers, Susanna L.; Nolan, David J.; Barbier, Andrew E.; Salemi, Marco

    2016-01-01

    Kaposi's sarcoma (KS) in HIV-infected individuals can have a wide range of clinical outcomes, from indolent skin tumors to a life-threatening visceral cancer. KS tumors contain endothelial-related cells and inflammatory cells that may be HIV-infected. In this study we tested if HIV evolutionary patterns distinguish KS tumor relatedness and progression. Multisite autopsies from participants who died from HIV-AIDS with KS prior to the availability of antiretroviral therapy were identified at the AIDS and Cancer Specimen Resource (ACSR). Two patients (KS1 and KS2) died predominantly from non-KS-associated disease and KS3 died due to aggressive and metastatic KS within one month of diagnosis. Skin and visceral tumor and nontumor autopsy tissues were obtained (n = 12). Single genome sequencing was used to amplify HIV RNA and DNA, which was present in all tumors. Independent HIV tumor clades in phylogenies differentiated KS1 and KS2 from KS3, whose sequences were interrelated by both phylogeny and selection. HIV compartmentalization was confirmed in KS1 and KS2 tumors; however, in KS3, no compartmentalization was observed among sampled tissues. While the sample size is small, the HIV evolutionary patterns observed in all patients suggest an interplay between tumor cells and HIV-infected cells which provides a selective advantage and could promote KS progression. PMID:27651732