Pacific NorthWest Regional Center of Excellence (PNWRCE)

Summary

Principal Investigator: Jay A Nelson
Abstract: The goal of this application is to establish the Pacific Northwest Regional Center of Excellence (PNWRCE) in NIAID Region X. The two inter-related but distinct PNWRCE themes that we have selected reflect not only the scientific strengths at our institutions but also the unmet needs that we perceive are absent in the NIAID biodefense and emerging disease program. The first theme "Identification of Age-Related Defects in the Immune System to Develop Vaccines and Supplemental Therapies" will include two projects. The overall goal of these projects is to develop new vaccines and immune supplemental therapies for immune vulnerable populations such as aged individuals. The first project a P01 will investigate the hypothesis that certain unifying manipulations can be performed to increase T cell immunity in immune vulnerable populations to a broad group of pathogens. The second project will develop a novel and effective vaccine platform for safely immunizing both healthy and vulnerable populations against YFV. The second theme will center on "The use of systems biology, functional genomics and genetics to characterize pathogen-host response for biodefense and emerging disease organisms." This theme will include four projects with the overall goal of using systems approaches to identify new targets and therapeutics for Category A-C agents. The goal of the first project a P01 is to use systems approaches to identify common host susceptibility alleles and signaling circuitry that enhance highly pathogenic pneumonic viruses and Ebola virus replication and pathogenesis and to identify key cellular targets and immune correlates that influence severe disease outcomes. The goal of the second project a P01 is focused on defining innate immune mechanisms, therapeutic targets, and antiviral compounds that limit flavivirus infection and pathogenesis. The third project an R01 will use systems approaches to characterize Francisella mutants that exhibit either altered intracellular growth rates or induce cellular apoptosis. The last project an RO1 will use a combination of genetic, biochemical, and computational approaches to elucidate B. pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease.
Funding Period: 2009-04-20 - 2015-02-28
more information: NIH RePORT

Top Publications

  1. pmc Status and access to the Collaborative Cross population
    Catherine E Welsh
    Department of Computer Science, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Mamm Genome 23:706-12. 2012
  2. pmc Immune responses to West Nile virus infection in the central nervous system
    Hyelim Cho
    Departments of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Viruses 4:3812-30. 2012
  3. pmc A reversed-phase capillary ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for comprehensive top-down/bottom-up lipid profiling
    Xiaoli Gao
    Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
    Anal Bioanal Chem 402:2923-33. 2012
  4. pmc Cell-intrinsic innate immune control of West Nile virus infection
    Michael S Diamond
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Trends Immunol 33:522-30. 2012
  5. pmc The broad-spectrum antiviral functions of IFIT and IFITM proteins
    Michael S Diamond
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Rev Immunol 13:46-57. 2013
  6. pmc IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling
    Helen M Lazear
    Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
    PLoS Pathog 9:e1003118. 2013
  7. pmc Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses
    Hyelim Cho
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Med 19:458-64. 2013
  8. pmc Modeling host genetic regulation of influenza pathogenesis in the collaborative cross
    Martin T Ferris
    Carolina Vaccine Institute, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS Pathog 9:e1003196. 2013
  9. pmc A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes
    Mehul S Suthar
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA
    PLoS Pathog 9:e1003168. 2013
  10. pmc Systems approaches to influenza-virus host interactions and the pathogenesis of highly virulent and pandemic viruses
    Marcus J Korth
    Department of Microbiology, School of Medicine, and Washington National Primate Research Center, University of Washington, Seattle, WA 98195 8070, USA
    Semin Immunol 25:228-39. 2013

Detail Information

Publications91

  1. pmc Status and access to the Collaborative Cross population
    Catherine E Welsh
    Department of Computer Science, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Mamm Genome 23:706-12. 2012
    ..Here we provide a description of the distribution efforts by the University of North Carolina Systems Genetics Core, Tel Aviv University, Israel and the University of Western Australia...
  2. pmc Immune responses to West Nile virus infection in the central nervous system
    Hyelim Cho
    Departments of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Viruses 4:3812-30. 2012
    ..We will focus on defining the current state of knowledge of WNV entry, tropism, and host immune response in the CNS, all of which affect the balance between injury and successful clearance...
  3. pmc A reversed-phase capillary ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) method for comprehensive top-down/bottom-up lipid profiling
    Xiaoli Gao
    Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
    Anal Bioanal Chem 402:2923-33. 2012
    ..Overall, the method provided either higher coverage of the lipidome, greater measurement sensitivity, or both, when compared to other approaches of global, untargeted lipid profiling based on chromatography coupled with MS...
  4. pmc Cell-intrinsic innate immune control of West Nile virus infection
    Michael S Diamond
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Trends Immunol 33:522-30. 2012
    ....
  5. pmc The broad-spectrum antiviral functions of IFIT and IFITM proteins
    Michael S Diamond
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Rev Immunol 13:46-57. 2013
    ..This Review focuses on recent advances in identifying the unique mechanisms of action of IFIT and IFITM proteins, which explain their broad-spectrum activity against the replication, spread and pathogenesis of a range of human viruses...
  6. pmc IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling
    Helen M Lazear
    Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
    PLoS Pathog 9:e1003118. 2013
    ..Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5...
  7. pmc Differential innate immune response programs in neuronal subtypes determine susceptibility to infection in the brain by positive-stranded RNA viruses
    Hyelim Cho
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, USA
    Nat Med 19:458-64. 2013
    ..Thus, neurons from evolutionarily distinct brain regions have unique innate immune signatures, which probably contribute to their relative permissiveness to infection...
  8. pmc Modeling host genetic regulation of influenza pathogenesis in the collaborative cross
    Martin T Ferris
    Carolina Vaccine Institute, University of North Carolina Chapel Hill, Chapel Hill, North Carolina, United States of America
    PLoS Pathog 9:e1003196. 2013
    ..We sequenced the coding regions of Mx1 in the eight CC founder strains, and identified a novel Mx1 allele that showed reduced ability to inhibit viral replication, while maintaining protection from weight loss...
  9. pmc A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes
    Mehul S Suthar
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA
    PLoS Pathog 9:e1003168. 2013
    ....
  10. pmc Systems approaches to influenza-virus host interactions and the pathogenesis of highly virulent and pandemic viruses
    Marcus J Korth
    Department of Microbiology, School of Medicine, and Washington National Primate Research Center, University of Washington, Seattle, WA 98195 8070, USA
    Semin Immunol 25:228-39. 2013
    ....
  11. pmc The RIG-I-like receptor LGP2 controls CD8(+) T cell survival and fitness
    Mehul S Suthar
    Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA
    Immunity 37:235-48. 2012
    ....
  12. pmc Spontaneous mutation of the Dock2 gene in Irf5-/- mice complicates interpretation of type I interferon production and antibody responses
    Whitney E Purtha
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    Proc Natl Acad Sci U S A 109:E898-904. 2012
    ..Thus, confirmation of the normal Dock2 genotype in circulating Irf5(-/-) mice is warranted, and our data may partly explain conflicting results in this field...
  13. pmc West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response
    Andrea Schuessler
    Australian Infectious Disease Research Centre, School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia
    J Virol 86:5708-18. 2012
    ..The results define a novel function of sfRNA in flavivirus pathogenesis via its contribution to viral evasion of the type I interferon response...
  14. pmc A hybrid approach to protein differential expression in mass spectrometry-based proteomics
    Xuan Wang
    Department of Statistics, Texas A and M University, 3143 TAMU, College Station, TX 77843, USA
    Bioinformatics 28:1586-91. 2012
    ..However, typical MS-based proteomics datasets have substantial proportions of missing observations, due at least in part to censoring of low intensities. This complicates intensity-based differential expression analysis...
  15. pmc In silico identification software (ISIS): a machine learning approach to tandem mass spectral identification of lipids
    Lars J Kangas
    Computational and Statistical Analytics Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
    Bioinformatics 28:1705-13. 2012
    ....
  16. pmc Age-related changes in CD8 T cell homeostasis and immunity to infection
    Janko Nikolich-Zugich
    Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724, United States
    Semin Immunol 24:356-64. 2012
    ..We specifically address phenotypic and numeric changes to the naïve CD8 T cell precursor pool, the impact of persistent viral infection(s) and inflammation, and contributions of the aging environment in which these cells are activated...
  17. pmc Induction of the cellular microRNA, Hs_154, by West Nile virus contributes to virus-mediated apoptosis through repression of antiapoptotic factors
    Jessica L Smith
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA
    J Virol 86:5278-87. 2012
    ....
  18. pmc Virus-infected alveolar epithelial cells direct neutrophil chemotaxis and inhibit their apoptosis
    Joanna P Rzepka
    Department of Biological Sciences, University of Idaho, Moscow, ID 83844 3051, USA
    Am J Respir Cell Mol Biol 46:833-41. 2012
    ..These studies provide new insight into the molecular mechanisms whereby alveolar epithelial cells direct the functions of PMNs during viral infection of the lung...
  19. pmc Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus
    Laurence Josset
    Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA
    MBio 4:e00165-13. 2013
    ..Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus...
  20. pmc Systems virology: host-directed approaches to viral pathogenesis and drug targeting
    G Lynn Law
    Department of Microbiology and Washington National Primate Research Center, University of Washington, Box 358070, Seattle, Washington 98195, USA
    Nat Rev Microbiol 11:455-66. 2013
    ..To realize these goals, pipettes and Petri dishes need to join forces with the powers of mathematics and computational biology...
  21. pmc A short hairpin RNA screen of interferon-stimulated genes identifies a novel negative regulator of the cellular antiviral response
    Jianqing Li
    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri, USA
    MBio 4:e00385-13. 2013
    ..Compared to prior ectopic ISG expression studies, our shRNA screen identified novel ISGs that restrict infection of WNV and other viruses and defined a new counterregulatory ISG, ASCC3, which tempers cell-intrinsic immunity...
  22. pmc Drug repurposing: a better approach for infectious disease drug discovery?
    G Lynn Law
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Curr Opin Immunol 25:588-92. 2013
    ..These new approaches have the potential to significantly reduce both the time and cost for infectious diseases drug discovery. ..
  23. pmc The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication
    Lindsay Hill-Batorski
    Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin Madison, Madison, Wisconsin, USA
    J Virol 87:13795-802. 2013
    ..Therefore, modulation of the cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV infection. ..
  24. pmc Deficient IFN signaling by myeloid cells leads to MAVS-dependent virus-induced sepsis
    Amelia K Pinto
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Pathog 10:e1004086. 2014
    ..Collectively, our findings establish the dominant role of type I IFN signaling in myeloid cells in restricting virus infection and controlling pathological inflammation and tissue injury. ..
  25. pmc The Collaborative Cross as a resource for modeling human disease: CC011/Unc, a new mouse model for spontaneous colitis
    Allison R Rogala
    Division of Laboratory Animal Medicine, University of North Carolina, Chapel Hill, NC, USA
    Mamm Genome 25:95-108. 2014
    ..This work demonstrates the utility of the CC as a source of models of human disease that arises through new combinations of alleles at susceptibility loci...
  26. pmc Inhibition of dengue virus replication by a class of small-molecule compounds that antagonize dopamine receptor d4 and downstream mitogen-activated protein kinase signaling
    Jessica L Smith
    Vaccine and Gene Therapy Institute, Oregon Health and Sciences University, Beaverton, Oregon, USA
    J Virol 88:5533-42. 2014
    ....
  27. pmc Vaccinia virus requires glutamine but not glucose for efficient replication
    Krystal A Fontaine
    Department of Microbiology, University of Washington, Seattle, Washington, USA
    J Virol 88:4366-74. 2014
    ..This study reveals the unique carbon utilization program implemented during poxvirus infection and provides a potential metabolic pathway to target viral replication...
  28. pmc Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: a model for rational arboviral vaccine design
    Christina L Gardner
    Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
    PLoS Negl Trop Dis 8:e2719. 2014
    ..Furthermore, we have identified a mutation at E2 position 79 as a promising candidate for inclusion in a CHIKV LAV. ..
  29. pmc Neutrophils are needed for an effective immune response against pulmonary rat coronavirus infection, but also contribute to pathology
    Anoria K Haick
    Department of Biological Sciences, University of Idaho, 875 Perimeter Dr, MS 3051, Moscow, ID 83844 3051, USA
    J Gen Virol 95:578-90. 2014
    ..This study demonstrated that while PMN are required for an effective antiviral response, they also contribute to lung pathology during RCoV infection. ..
  30. pmc The tiers and dimensions of evasion of the type I interferon response by human cytomegalovirus
    Lisi Amsler
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 Northwest 185th Avenue, Beaverton, OR 97006, USA
    J Mol Biol 425:4857-71. 2013
    ....
  31. pmc Systems immunogenetics of vaccines
    Michael Mooney
    Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health and Science University, Oregon, United States
    Semin Immunol 25:124-9. 2013
    ....
  32. pmc Flaviviruses are sensitive to inhibition of thymidine synthesis pathways
    Matthew A Fischer
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA
    J Virol 87:9411-9. 2013
    ..Our data reveal thymidine synthesis pathways as new and unexpected therapeutic targets for antiflaviviral drug development. ..
  33. pmc Differentiated phenotypes of primary murine alveolar epithelial cells and their susceptibility to infection by respiratory viruses
    Lemme P Kebaabetswe
    Department of Biological Sciences, University of Idaho, Moscow, ID 83844 3051, USA
    Virus Res 175:110-9. 2013
    ..This in vitro model will be critical for future studies to determine the roles of these specialized cell types in the pathogenesis of respiratory viral infection...
  34. pmc Chikungunya virus infection results in higher and persistent viral replication in aged rhesus macaques due to defects in anti-viral immunity
    Ilhem Messaoudi
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America
    PLoS Negl Trop Dis 7:e2343. 2013
    ..Taken together these data suggest that the reduced immune responses in the aged animals promotes long-term virus persistence in CHIKV-LR infected Rhesus monkeys. ..
  35. pmc Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors
    Suchita Bhattacharyya
    Nomis Center for Immunobiology and Microbial Pathogenesis, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
    Cell Host Microbe 14:136-47. 2013
    ..Correspondingly, a TAM kinase inhibitor antagonizes the infection of wild-type DCs. Thus, TAM receptors are engaged by viruses in order to attenuate type I IFN signaling and represent potential therapeutic targets. ..
  36. pmc Pattern recognition receptor MDA5 modulates CD8+ T cell-dependent clearance of West Nile virus from the central nervous system
    Helen M Lazear
    Departments of Medicine
    J Virol 87:11401-15. 2013
    ..Our studies suggest that MDA5 in the immune priming environment shapes optimal CD8(+) T cell activation and subsequent clearance of WNV from the CNS. ..
  37. pmc Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques
    Emmie de Wit
    Laboratory of Virology, Rocky Mountain Veterinary Branch, and Microscopy Unit, Research Technologies Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840
    Proc Natl Acad Sci U S A 110:16598-603. 2013
    ..This tropism of MERS-CoV for the lower respiratory tract may explain the severity of the disease observed in humans and the, up to now, limited human-to-human transmission. ..
  38. ncbi Mathematical models of viral latency
    Christian Selinger
    Department of Microbiology, University of Washington, Box 358070, Seattle, WA 98195 8070, USA Electronic address
    Curr Opin Virol 3:402-7. 2013
    ....
  39. ncbi RNA viruses can hijack vertebrate microRNAs to suppress innate immunity
    Derek W Trobaugh
    Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA
    Nature 506:245-8. 2014
    ..We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity...
  40. pmc Marburg virus VP35 can both fully coat the backbone and cap the ends of dsRNA for interferon antagonism
    Shridhar Bale
    Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA
    PLoS Pathog 8:e1002916. 2012
    ....
  41. pmc Induction of IFN-beta and the innate antiviral response in myeloid cells occurs through an IPS-1-dependent signal that does not require IRF-3 and IRF-7
    Stephane Daffis
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Pathog 5:e1000607. 2009
    ....
  42. pmc Inhibition of dengue virus infections in cell cultures and in AG129 mice by a small interfering RNA targeting a highly conserved sequence
    David A Stein
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR, USA
    J Virol 85:10154-66. 2011
    ..Overall, the data indicate that DC-3 siRNA represents a useful research reagent and has potential as a novel approach to therapeutic intervention against the genetically diverse dengue viruses...
  43. pmc Beta interferon controls West Nile virus infection and pathogenesis in mice
    Helen M Lazear
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Box 8051, St Louis, MO 63110, USA
    J Virol 85:7186-94. 2011
    ..Collectively, these results suggest that IFN-β controls WNV pathogenesis by restricting infection in key cell types and by modulating T cell regulatory networks...
  44. pmc Comparative pathogenesis of three human and zoonotic SARS-CoV strains in cynomolgus macaques
    Barry Rockx
    Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America
    PLoS ONE 6:e18558. 2011
    ..This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use...
  45. pmc Repeated in vivo stimulation of T and B cell responses in old mice generates protective immunity against lethal West Nile virus encephalitis
    Jennifer L Uhrlaub
    Department of Immunobiology, College of Medicine, University of Arizona, Tucson, AZ 85719, USA
    J Immunol 186:3882-91. 2011
    ....
  46. pmc Separation and classification of lipids using differential ion mobility spectrometry
    Alexandre A Shvartsburg
    Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
    J Am Soc Mass Spectrom 22:1146-55. 2011
    ..These results open the door for application of FAIMS to lipids, particularly in shotgun lipidomics and targeted analyses of bioactive lipids...
  47. pmc Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection
    James D Brien
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Pathog 7:e1002230. 2011
    ..Thus, IRF-1 restricts WNV infection by modulating the expression of innate antiviral effector molecules while shaping the antigen-specific CD8(+) T cell response...
  48. pmc A statistical selection strategy for normalization procedures in LC-MS proteomics experiments through dataset-dependent ranking of normalization scaling factors
    Bobbie Jo M Webb-Robertson
    Pacific Northwest National Laboratory, USA
    Proteomics 11:4736-41. 2011
    ....
  49. pmc Functional genomics reveals the induction of inflammatory response and metalloproteinase gene expression during lethal Ebola virus infection
    Cristian Cilloniz
    Department of Microbiology, School of Medicine, University of Washington, Box 358070, Seattle, WA 98195 8070, USA
    J Virol 85:9060-8. 2011
    ..To our knowledge, this is the first study that clearly defines unique molecular signatures associated with Ebola virus lethality...
  50. pmc One naive T cell, multiple fates in CD8+ T cell differentiation
    Carmen Gerlach
    Division of Immunology, Central Microarray Facility, and Bioinformatics and Statistics Group, The Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands
    J Exp Med 207:1235-46. 2010
    ..Instead, for both low and high avidity T cells, individual naive T cells have multiple fates and can differentiate into effector and memory T cell subsets...
  51. pmc The innate immune adaptor molecule MyD88 restricts West Nile virus replication and spread in neurons of the central nervous system
    Kristy J Szretter
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Virol 84:12125-38. 2010
    ..Our experiments suggest that MyD88 restricts WNV by inhibiting replication in subsets of cells and modulating expression of chemokines that regulate immune cell migration into the central nervous system...
  52. pmc Wanted, dead or alive: new viral vaccines
    Ian J Amanna
    Najít Technologies, Inc, Suite 200, Portland, OR 97201, USA
    Antiviral Res 84:119-30. 2009
    ..By building a better understanding of how successful vaccines work, we hope to develop better "next-generation" vaccines as well as new vaccines against HIV--a pathogen of global importance for which no licensed vaccine currently exists...
  53. pmc Transformation of Candida albicans with a synthetic hygromycin B resistance gene
    Luiz R Basso
    Division of Infectious Diseases, Department of Medicine, Oregon Health and Science University, Portland, OR 97239 0398, USA
    Yeast 27:1039-48. 2010
    ..CaHygB should be a useful tool for genetic manipulation of different C. albicans strains, including clinical isolates...
  54. pmc Lack of original antigenic sin in recall CD8(+) T cell responses
    Dietmar Zehn
    Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
    J Immunol 184:6320-6. 2010
    ..Taken together, our data show that the phenomenon of original antigenic sin does not occur in all heterologous infections...
  55. pmc The use of RNAi-based screens to identify host proteins involved in viral replication
    Alec J Hirsch
    Vaccine and Gene Therapy Institute, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA
    Future Microbiol 5:303-11. 2010
    ..This review summarizes the methods used in RNAi-based screening for host factors involved in virus replication, and discusses published examples of such screens...
  56. pmc 2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members
    Stephane Daffis
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nature 468:452-6. 2010
    ..Differential methylation of cytoplasmic RNA probably serves as an example for pattern recognition and restriction of propagation of foreign viral RNA in host cells...
  57. pmc High-content assay to identify inhibitors of dengue virus infection
    David Shum
    HTS Core Facility, Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
    Assay Drug Dev Technol 8:553-70. 2010
    ..In summary, this assay offers the opportunity to screen libraries of chemical compounds, in an effort to identify and develop novel drug candidates against DENV infections...
  58. pmc Transcriptomic analysis reveals a mechanism for a prefibrotic phenotype in STAT1 knockout mice during severe acute respiratory syndrome coronavirus infection
    Gregory A Zornetzer
    Department of Microbiology, School of Medicine, University of Washington, Box 358070, Seattle, WA 98195 8070, USA
    J Virol 84:11297-309. 2010
    ..We propose that a combination of impaired viral clearance and T-cell/macrophage dysregulation causes the formation of prefibrotic lesions in the lungs of rMA15-infected STAT1-/- mice...
  59. pmc Immune memory and aging: an infinite or finite resource?
    Janko Nikolich-Zugich
    Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, 1656 E Mabel St, Tucson, AZ 85719, USA
    Curr Opin Immunol 22:535-40. 2010
    ....
  60. pmc Contributions of humoral and cellular immunity to vaccine-induced protection in humans
    Ian J Amanna
    Najít Technologies, Inc, Beaverton, OR 97006, USA
    Virology 411:206-15. 2011
    ..In this review, we will discuss the relative contributions of virus-specific T cell and B cell responses to vaccine-mediated protection against disease...
  61. pmc The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase
    Peter Halfmann
    Department of Pathobiological Sciences, School of Veterinary Medicine, Influenza Research Institute, University of Wisconsin Madison, WI, USA
    J Infect Dis 204:S953-6. 2011
    ..Similar inhibition was not observed in HeLa cells, suggesting cell type-specific differences in signal transduction...
  62. pmc Increased apoptosis, curtailed expansion and incomplete differentiation of CD8+ T cells combine to decrease clearance of L. monocytogenes in old mice
    Megan J Smithey
    Department of Immunobiology and Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85719, USA
    Eur J Immunol 41:1352-64. 2011
    ....
  63. pmc Lifelong persistent viral infection alters the naive T cell pool, impairing CD8 T cell immunity in late life
    Megan J Smithey
    Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ 85724, USA
    J Immunol 189:5356-66. 2012
    ....
  64. pmc A point-source norovirus outbreak caused by exposure to fomites
    Kimberly K Repp
    Washington County Department of Health and Human Services, Hillsboro, OR, USA
    J Infect Dis 205:1639-41. 2012
    ..When feasible, we recommend dedicated bathrooms for sick persons and informing cleaning staff (professional or otherwise) about the need for adequate environmental sanitation of surfaces and fomites to prevent spread...
  65. pmc IL-1β signaling promotes CNS-intrinsic immune control of West Nile virus infection
    HILARIO J RAMOS
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington, United States of America
    PLoS Pathog 8:e1003039. 2012
    ....
  66. pmc A flow cytometry-based assay for quantifying non-plaque forming strains of yellow fever virus
    Erika Hammarlund
    Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, United States of America
    PLoS ONE 7:e41707. 2012
    ....
  67. pmc 2'-O methylation of the viral mRNA cap by West Nile virus evades ifit1-dependent and -independent mechanisms of host restriction in vivo
    Kristy J Szretter
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United Stated of America
    PLoS Pathog 8:e1002698. 2012
    ....
  68. pmc Antibody discovery ex vivo accelerated by the LacO/LacI regulatory network
    Munehisa Yabuki
    Department of Immunology, University of Washington School of Medicine, Seattle, Washington, USA
    PLoS ONE 7:e36032. 2012
    ..mAb discovery is rapid and humanization is straightforward, establishing the utility of the DTLacO platform for identification of mAbs for therapeutic and other applications...
  69. pmc Age-associated alterations in CD8α+ dendritic cells impair CD8 T-cell expansion in response to an intracellular bacterium
    Gang Li
    Department of Immunobiology and the Arizona Center on Aging, University of Arizona College of Medicine, Tucson, AZ 85724, USA
    Aging Cell 11:968-77. 2012
    ..These results suggest that age-associated changes in antigen uptake, pathogen sensing, and/or antigen presentation contribute to impaired adaptive immune responses to microbial pathogens with aging...
  70. pmc Into the eye of the cytokine storm
    Jennifer R Tisoncik
    Department of Microbiology, University of Washington, Seattle, Washington, USA
    Microbiol Mol Biol Rev 76:16-32. 2012
    ....
  71. pmc Infectious clones of novel lineage 1 and lineage 2 West Nile virus strains WNV-TX02 and WNV-Madagascar
    Mehul S Suthar
    Department of Immunology, University of Washington School of Medicine, Seattle, WA, USA
    J Virol 86:7704-9. 2012
    ..These infectious clones provide new reagents to study flavivirus immune regulation and pathogenesis...
  72. pmc Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate
    Christina L Gardner
    Center for Vaccine Research and Dept of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, USA
    Virology 425:103-12. 2012
    ..Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent...
  73. pmc A statistical method for assessing peptide identification confidence in accurate mass and time tag proteomics
    Jeffrey R Stanley
    Department of Statistics, Texas A and M University, College Station, Texas 77840, United States
    Anal Chem 83:6135-40. 2011
    ..STAC is freely available for download, as both a command line and a Windows graphical application...
  74. pmc Virus infection rapidly activates the P58(IPK) pathway, delaying peak kinase activation to enhance viral replication
    Alan G Goodman
    Department of Cellular and Molecular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, Spain
    Virology 417:27-36. 2011
    ..Together, our study demonstrates how computational modeling can guide experimental design to further understand a specific metabolic signaling pathway during viral infection in a mammalian system...
  75. pmc Differential microRNA expression and virulence of avian, 1918 reassortant, and reconstructed 1918 influenza A viruses
    Yu Li
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    Virology 421:105-13. 2011
    ..This study suggests that virulence of highly pathogenic influenza viruses may be mediated in part by cellular microRNA through dysregulation of genes critical to the inflammatory process...
  76. pmc A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge
    Meagan Bolles
    Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
    J Virol 85:12201-15. 2011
    ....
  77. pmc Comprehensive proteomic analysis of influenza virus polymerase complex reveals a novel association with mitochondrial proteins and RNA polymerase accessory factors
    Birgit G Bradel-Tretheway
    Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195, USA
    J Virol 85:8569-81. 2011
    ..Overall, this study has shed light into the complex contributions of the IAV polymerase to host cell pathogenicity and allows for direct investigations into the biological significance of these newly described interactions...
  78. pmc The interferon-inducible gene viperin restricts West Nile virus pathogenesis
    Kristy J Szretter
    Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8051, St Louis, MO 63110, USA
    J Virol 85:11557-66. 2011
    ..Our experiments suggest that viperin restricts the infection of WNV in a tissue- and cell-type-specific manner and may be an important ISG for controlling viral infections that cause CNS disease...
  79. pmc Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
    Roland Zust
    Institute of Immunobiology, Kantonal Hospital St Gallen, St Gallen, Switzerland
    Nat Immunol 12:137-43. 2011
    ..This link between Mda5-mediated sensing of viral RNA and 2'-O-methylation of mRNA suggests that RNA modifications such as 2'-O-methylation provide a molecular signature for the discrimination of self and non-self mRNA...
  80. pmc A temporal role of type I interferon signaling in CD8+ T cell maturation during acute West Nile virus infection
    Amelia K Pinto
    Department of Medicine, Washington University School of Medicine, St Louis, Missouri, United States of America
    PLoS Pathog 7:e1002407. 2011
    ..Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8(+) T cell response at a stage distinct from the initial priming event...
  81. pmc RIG-I like receptors in antiviral immunity and therapeutic applications
    Renee C Ireton
    Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA
    Viruses 3:906-19. 2011
    ....
  82. pmc Comparative analysis and visualization of multiple collinear genomes
    Jeremy R Wang
    Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
    BMC Bioinformatics 13:S13. 2012
    ....