Molecular Biology Of A Surface-Exposed Protein Family Of Bartonella Bacilliformis, 2017 University of Montana
Molecular Biology Of A Surface-Exposed Protein Family Of Bartonella Bacilliformis, Hannah Fay
Undergraduate Theses and Professional Papers
Bartonella bacilliformis is a gram negative alpha-proteobacterium native to the Andes of South America. Bartonella causes Carrion’s disease, a potentially life threatening disease transmitted by the sand fly. It has a mortality rate of 88% when untreated and 10% when treated. Diagnostics and control measures for the disease are underdeveloped and no vaccine is available. Recent outbreaks indicate that the range of the pathogen is increasing with nearly 1.7 million people in western South America at risk. Little is known about the epidemiology and pathogenesis of B. bacilliformis. Recent research done by UC San Diego found a paralogous ...
The Case For Selection At Ccr5-Δ32, 2016 Broad Institute; Harvard Medical School
The Case For Selection At Ccr5-Δ32, Pardis Sabeti, Emily C. Walsh, Stephen F. Schaffner, Patrick Varilly, Ben Fry, Holli Hutcheson, Mike Cullen, Tarjei S. Mikkelsen, Jessica Roy, Nick Patterson, Richard Cooper, David Reich, David Altshuler, Stephen J. O'Brien, Eric S. Lander
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Δ32 arose within the past 1,000 y and rose to its present high frequency (5%–14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with ...
Role Of Exonic Variation In Chemokine Receptor Genes On Aids: Ccrl2 F167y Association With Pneumocystis Pneumonia, 2016 National Cancer Institute at Frederick
Role Of Exonic Variation In Chemokine Receptor Genes On Aids: Ccrl2 F167y Association With Pneumocystis Pneumonia, Ping An, Rongling Li, Ji Ming Wang, Teizo Yoshimura, Munehisa Takahashi, Ram Samudralal, Stephen J. O'Brien, John Phair, James J. Goedert, Gregory D. Kirk, Jennifer L. Troyer, Efe Sezgin, Susan Buchbinder, Sharyne Donfield, George W. Nelson, Cheryl Winkler
Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 andCCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In ...
Regulatory Polymorphisms In The Cyclophilin A Gene, Ppia, Accelerate Progression To Aids, 2016 National Cancer Institute at Frederick
Regulatory Polymorphisms In The Cyclophilin A Gene, Ppia, Accelerate Progression To Aids, Ping An, Li Hua Wang, Holli Hutcheson-Dilks, George Nelson, Sharyne Donfield, James J. Goedert, Charles Rinaldo, Susan Buchbinder, Gregory D. Kirk, Stephen J. O'Brien, Cheryl Winkler
Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA), is incorporated into the HIV type 1 (HIV-1) virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs) and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4) in perfect linkage disequilibrium were associated with more rapid CD4+ T-cell loss (relative hazard = 3.7 ...
Polymorphisms Of Cul5 Are Associated With Cd4+ T Cell Loss In Hiv-1 Infected Individuals, 2016 National Cancer Institute at Frederick
Polymorphisms Of Cul5 Are Associated With Cd4+ T Cell Loss In Hiv-1 Infected Individuals, Ping An, Priya Duggal, Li Hua Wang, Stephen J. O'Brien, Sharyne Donfield, James J. Goedert, John Phair, Susan Buchbinder, Gregory D. Kirk, Cheryl Winkler
Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters ...
Genomically Intact Endogenous Feline Leukemia Viruses Of Recent Origin, 2016 National Cancer Institute at Frederick
Genomically Intact Endogenous Feline Leukemia Viruses Of Recent Origin, Alfred L. Roca, Jill Pecon-Slattery, Stephen J. O'Brien
We isolated and sequenced two complete endogenous feline leukemia viruses (enFeLVs), designated enFeLV-AGTT and enFeLV-GGAG. In enFeLV-AGTT, the open reading frames are reminiscent of a functioning FeLV genome, and the 5′ and 3′ long terminal repeat sequences are identical. Neither endogenous provirus is genetically fixed in cats but polymorphic, with 8.9 and 15.2% prevalence for enFeLV-AGTT and enFeLV-GGAG, respectively, among a survey of domestic cats. Neither provirus was found in the genomes of related species of the Felis genus, previously shown to harbor enFeLVs. The absence of mutational divergence, polymorphic incidence in cats, and absence in related species ...
Genomic Organization, Sequence Divergence, And Recombination Of Feline Immunodeficiency Virus From Lions In The Wild, 2016 National Cancer Institute at Frederick
Genomic Organization, Sequence Divergence, And Recombination Of Feline Immunodeficiency Virus From Lions In The Wild, Jill Pecon-Slattery, Carrie L. Mccracken, Jennifer L. Troyer, Sue Vandewoude, Melody E. Roelke, Kerry Sondgeroth, Christiaan Winterbach, Stephen J. O'Brien
Feline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion.
In this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes isolated from free-ranging lions ...
Genetic Variants In Nuclear-Encoded Mitochondrial Genes Influence Aids Progression, 2016 National Cancer Institute at Frederick
Genetic Variants In Nuclear-Encoded Mitochondrial Genes Influence Aids Progression, Sher L. Hendrickson, J. A. Lautenberger, Leslie Wei Chinn, Michael Malasky, Lawrence Kingsley, James J. Goedert, Gregory D. Kirk, Edward Gomperts, Susan Buchbinder, Jennifer L. Troyer, Stephen J. O'Brien
Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.
Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping ...
Genetic Characterization Of Feline Leukemia Virus From Florida Panthers, 2016 National Cancer Institute at Frederick
Genetic Characterization Of Feline Leukemia Virus From Florida Panthers, Meredith Brown, Mark W. Cunningham, Alfred L. Roca, Jennifer L. Troyer, Warren E. Johnson, Stephen J. O'Brien
From 2002 through 2005, an outbreak of feline leukemia virus (FeLV) occurred in Florida panthers (Puma concolor coryi). Clinical signs included lymphadenopathy, anemia, septicemia, and weight loss; 5 panthers died. Not associated with FeLV outcome were the genetic heritage of the panthers (pure Florida vs. Texas/Florida crosses) and co-infection with feline immunodeficiency virus. Genetic analysis of panther FeLV, designated FeLV-Pco, determined that the outbreak likely came from 1 cross-species transmission from a domestic cat. The FeLV-Pco virus was closely related to the domestic cat exogenous FeLV-A subgroup in lacking recombinant segments derived from endogenous FeLV. FeLV-Pco sequences were most ...
Evidence Of Natural Bluetongue Virus Infection Among African Carnivores, 2016 University of California - Davis
Evidence Of Natural Bluetongue Virus Infection Among African Carnivores, Kathleen A. Alexander, N. James Maclachlan, Pieter W. Kat, Carol House, Stephen J. O'Brien, Nicholas W. Lerche, Mary Sawyer, Laurence G. Frank, Kay Holekamp, Laura Smale, J. Weldon Mcnutt, M. Karen Laurenson, M. G. L. Mills, Bennie I. Osburn
Bluetongue is an International Office of Epizootics List A disease described as the century's most economically devastating affliction of sheep. Bluetongue (BLU) viruses were thought to infect only ruminants, shrews, and some rodents, but recently, inadvertent administration of BLU virus-contaminated vaccine resulted in mortality and abortion among domestic dogs. We present evidence of natural BLU virus infection among African carnivores that dramatically widens the spectrum of susceptible hosts. We hypothesize that such infection occurred after ingestion of meat and organs from BLU virus infected prey species. The effect of BLU virus on endangered carnivores such as the cheetah and ...
Effect Of A Single Amino Acid Change In Mhc Class I Molecules On The Rate Of Progression To Aids, 2016 National Cancer Institute at Frederick
Effect Of A Single Amino Acid Change In Mhc Class I Molecules On The Rate Of Progression To Aids, Xiaojiang Gao, George W. Nelson, Peter Karacki, Maureen P. Martin, John Phair, Richard A. Kaslow, James J. Goedert, Susan Buchbinder, Keith Hoots, David Vlahov, Stephen J. O'Brien, Mary Carrington
Background From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. Methods Genotyping of HLA class I loci was ...
Common Genetic Variation And The Control Of Hiv-1 In Humans, 2016 Duke University
Common Genetic Variation And The Control Of Hiv-1 In Humans, Jacques Fellay, Dongliang Ge, Kevin V. Shianna, Sara Colombo, Bruno Ledergerber, Elizabeth T. Cirulli, Thomas J. Urban, Kunlin Zhang, Curtis Gumbs, Jason P. Smith, Antonella Castagna, Alessandro Cozzi-Lepri, Andrea De Luca, Philippa Easterbrook, Huldrych F. Gunthard, Simon Mallal, Cristina Mussini, Judith Dalmau, Javier Martinez-Picado, Jose M. Miro, Niels Obel, Steven M. Wolinsky, Jeremy J. Martinson, Roger Detels, Joseph Margolick, Lisa Jacobson, Patrick Descombes, Stylianos E. Antonarakis, Jacques S. Beckmann, Stephen J. O'Brien, Norman L. Letvin, Andrew J. Mcmichael, Barton F. Haynes, Mary Carrington, Sheng Feng, Amalio Telenti, David B. Goldstein
To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant ...
A Population-Based Study To Investigate Host Genetic Factors Associated With Hepatitis B Infection And Pathogenesis In The Chinese Population, Zheng Zheng, Li Guan, Ping An, Shan Sun, Stephen J. O'Brien, Cheryl Winkler
Background Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5–6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options. Methods/Design ...
A Genome-To-Genome Analysis Of Associations Between Human Genetic Variation, Hiv-1 Sequence Diversity, And Viral Control, 2016 Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Eotvos Lorand University and the Hungarian Academy of Sciences - Budapest; Swiss Institute of Bioinformatics
A Genome-To-Genome Analysis Of Associations Between Human Genetic Variation, Hiv-1 Sequence Diversity, And Viral Control, Istvan Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. Mclaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio Lopez-Galindez, Concepcion Casado, Andri Rauch, Huldrych F. Gunthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolo Fusi, Zoltan Kutalik, Todd M. Allen, Viktor Muller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay
HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10−12). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for ...2.4>
Vaccination Strategies For Small Worlds, 2016 Ohio University - Main Campus
Vaccination Strategies For Small Worlds, Winfried Just, Hannah L. Callender
Annual Symposium on Biomathematics and Ecology: Education and Research
No abstract provided.
Modeling Cross-Species Extrapolation Of Inhalation Anthrax For Risk Assessment Purposes, 2016 University of St. Francis
Modeling Cross-Species Extrapolation Of Inhalation Anthrax For Risk Assessment Purposes, Megan O. Powell
Annual Symposium on Biomathematics and Ecology: Education and Research
No abstract provided.
The Nih-Niaid Schistosomiasis Resource Center At The Biomedical Research Institute: Molecular Redux., 2016 George Washington University
The Nih-Niaid Schistosomiasis Resource Center At The Biomedical Research Institute: Molecular Redux., James J Cody, Wannaporn Ittiprasert, André N Miller, Lucie Henein, Margaret M Mentink-Kane, Michael H. Hsieh
Urology Faculty Publications
Schistosomiasis remains a health burden in many parts of the world. The complex life cycle of Schistosoma parasites and the economic and societal conditions present in endemic areas make the prospect of eradication unlikely in the foreseeable future. Continued and vigorous research efforts must therefore be directed at this disease, particularly since only a single World Health Organization (WHO)-approved drug is available for treatment. The National Institutes of Health (NIH)-National Institute of Allergy and Infectious Diseases (NIAID) Schistosomiasis Resource Center (SRC) at the Biomedical Research Institute provides investigators with the critical raw materials needed to carry out this ...
Hiv-1 Integrates Widely Throughout The Genome Of The Human Blood Fluke Schistosoma Mansoni., 2016 George Washington University
Hiv-1 Integrates Widely Throughout The Genome Of The Human Blood Fluke Schistosoma Mansoni., Sutas Suttiprapa, Gabriel Rinaldi, Isheng J Tsai, Victoria H. Mann, Larisa Dubrovsky, Hong-Bin Yan, Nancy Holroyd, Thomas Huckvale, Caroline Durrant, Anna V Protasio, Tatiana Pushkarsky, Sergey Iordanskiy, Matthew Berriman, Michael I. Bukrinsky, Paul J. Brindley
Microbiology, Immunology, and Tropical Medicine Faculty Publications
Schistosomiasis is the most important helminthic disease of humanity in terms of morbidity and mortality. Facile manipulation of schistosomes using lentiviruses would enable advances in functional genomics in these and related neglected tropical diseases pathogens including tapeworms, and including their non-dividing cells. Such approaches have hitherto been unavailable. Blood stream forms of the human blood fluke, Schistosoma mansoni, the causative agent of the hepatointestinal schistosomiasis, were infected with the human HIV-1 isolate NL4-3 pseudotyped with vesicular stomatitis virus glycoprotein. The appearance of strong stop and positive strand cDNAs indicated that virions fused to schistosome cells, the nucleocapsid internalized and the ...
Viral Zoonoses That Fly With Bats: A Review, 2016 Universidad de Cordoba, Monteria, Colombia
Viral Zoonoses That Fly With Bats: A Review, Alfonso Calderon, Camilo Guzman, Jorge Salazar-Bravo, Luiz Tadeu Figueiredo, Salim Mattar, German Arrieta
MANTER: Journal of Parasite Biodiversity
Emerging infectious diseases are a growing threat to human health and a great challenge for global medical attention systems. Governmental agencies in tropical regions with abundant zoonotic pathogens should implement an active vigilance/monitoring model in bat reservoir populations because of their species richness, abundance and dispersal capabilities. Chiropterans represent approximately 20% of all mammal species, the second largest order in terms of number of species after rodents. Importantly, bats constitute natural reservoirs for potential infection of humans of several infectious disease agents such as Coronavirus, Filovirus, Lyssavirus, Paramyxovirus, and Flavivirus. Local disease outbreaks caused by new pathogens can expand ...
A Test Of The Effects Of Androgens On Immunity: No Relationship Between 11-Keto Testosterone And Immune Performance In Bluegill Sunfish (Lepomis Macrochirus), 2016 The University of Western Ontario
A Test Of The Effects Of Androgens On Immunity: No Relationship Between 11-Keto Testosterone And Immune Performance In Bluegill Sunfish (Lepomis Macrochirus), John W. Loggie
Electronic Thesis and Dissertation Repository
The posited immunosuppressive effects of androgens are a key component of the immunocompetence handicap hypothesis (ICHH). My thesis uses bluegill sunfish (Lepomis macrochirus) to test two predictions arising from this hypothesis: (1) natural concentrations of the androgen 11-keto testosterone (11-KT) will be negatively related with immunity, and (2) an immunochallenge will lower 11-KT concentration. I found no evidence for a relationship between natural 11-KT concentration and measures of immunity (leukocyte counts, respiratory burst, cytokine gene expression), and an immunochallenge with Vibrio vaccine did not affect 11-KT concentration. I performed a meta-analysis of immunochallenge studies to help interpret my results, and ...