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  1. AU="Ruth R. Montgomery"
  2. AU=Jurkovic D
  3. AU="Bernhardi, Rommy von"
  4. AU="Senthi, Bibi"
  5. AU="Sipe, Brian W"
  6. AU="Ajose, Azeezat O"
  7. AU="Samira Mellah"
  8. AU="Al-Embideen S." AU="Al-Embideen S."
  9. AU="Kushiro, Tetsuo"
  10. AU="Spec, Andrej"
  11. AU="Salaniwal, Arul"
  12. AU="Epps, Chad A."
  13. AU=Brandt Ulrich
  14. AU="Kim, Hoyong"
  15. AU="Klas Bratteby"
  16. AU="Kim, Sae-Hoon"
  17. AU=Spivak Jerry L
  18. AU="Joel, Anjana"
  19. AU="Hill, William"
  20. AU="Ken M. Cadigan"
  21. AU="Lee, Hyun-Shik"
  22. AU="Martini, Denise"
  23. AU=Aziz Noreen M
  24. AU="Ho, Tony"
  25. AU=Barzilay Joshua I.
  26. AU="Ishizaka, Alessio"
  27. AU="Chao, Pei-Dawn Lee"
  28. AU="Rosa Gouveia"

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  1. Artikel ; Online: In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease

    Megan E. Cahill / Mark Loeb / Andrew T. Dewan / Ruth R. Montgomery

    Vaccines, Vol 8, Iss 744, p

    2020  Band 744

    Abstract: West Nile virus (WNV) is a mosquito-borne virus which causes symptomatic disease in a minority of infected humans. To identify novel genetic variants associated with severe disease, we utilized data from an existing case-control study of WNV and included ...

    Abstract West Nile virus (WNV) is a mosquito-borne virus which causes symptomatic disease in a minority of infected humans. To identify novel genetic variants associated with severe disease, we utilized data from an existing case-control study of WNV and included population controls for an expanded analysis. We conducted imputation and gene-gene interaction analysis in the largest and most comprehensive genetic study conducted to date for West Nile neuroinvasive disease (WNND). Within the imputed West Nile virus dataset (severe cases n = 381 and asymptomatic/mild controls = 441), we found novel loci within the MCF.2 Cell Line Derived Transforming Sequence Like ( MCF2L ) gene (rs9549655 and rs2297192) through the individual loci analyses, although none reached statistical significance. Incorporating population controls from the Wisconsin Longitudinal Study on Aging (n = 9012) did not identify additional novel variants, a possible reflection of the cohort’s inclusion of individuals who could develop mild or severe WNV disease upon infection. Many of the top gene-gene interaction results were intergenic, with currently undefined biological roles, highlighting the need for further investigation into these regions and other identified gene targets in severe WNND. Further studies including larger sample sizes and more diverse populations reflective of those at risk are needed to fully understand the genetic architecture of severe WNDD and provide guidance on viable targets for therapeutic and vaccine development.
    Schlagwörter West Nile virus ; West Nile neuroinvasive disease ; genome-wide association study ; gene-gene interactions ; disease severity ; Medicine ; R
    Thema/Rubrik (Code) 572
    Sprache Englisch
    Erscheinungsdatum 2020-12-01T00:00:00Z
    Verlag MDPI AG
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  2. Artikel ; Online: Design and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder

    Breanne E. Biondi / Subhasis Mohanty / Brent Vander Wyk / Ruth R. Montgomery / Albert C. Shaw / Sandra A. Springer

    Contemporary Clinical Trials Communications, Vol 21, Iss , Pp 100704- (2021)

    2021  

    Abstract: Background: Opioid use disorder (OUD) negatively impacts the HIV continuum of care for persons living with HIV. Medication treatment for OUD (MOUD) may have differential biological effects in individuals with HIV and OUD. To address the question of ... ...

    Abstract Background: Opioid use disorder (OUD) negatively impacts the HIV continuum of care for persons living with HIV. Medication treatment for OUD (MOUD) may have differential biological effects in individuals with HIV and OUD. To address the question of modulation of immune responses by MOUDs, we describe state of the art systems biology approaches to carry out the first prospective, longitudinal study of persons with and without HIV infection with OUD initiating MOUD. Methods: A prospective cohort study of persons with DSM-5 diagnosed OUD who are living with and without HIV infection and initiating treatment with methadone or buprenorphine is underway to assess biological effects of these medications on immunobiological outcomes. Results: We describe the recruitment, laboratory, and statistical methods of this study as well as the protocol details. Of those screened for enrollment into the study, 468 (36%) were eligible and 135 were enrolled thus far. Retention through month 6 has been high at 80%. Conclusions: This study will use state of the art systems biology approaches to carry out the first prospective, longitudinal studies of persons living with and without HIV with DSM-5 OUD initiating treatment with MOUD.
    Schlagwörter Opioid use disorder ; HIV ; Medication treatment for opioid use disorder ; Buprenorphine ; Methadone ; Medicine (General) ; R5-920
    Thema/Rubrik (Code) 360
    Sprache Englisch
    Erscheinungsdatum 2021-03-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  3. Artikel ; Online: Single-cell immunophenotyping of the skin lesion erythema migrans identifies IgM memory B cells

    Ruoyi Jiang / Hailong Meng / Khadir Raddassi / Ira Fleming / Kenneth B. Hoehn / Kenneth R. Dardick / Alexia A. Belperron / Ruth R. Montgomery / Alex K. Shalek / David A. Hafler / Steven H. Kleinstein / Linda K. Bockenstedt

    JCI Insight, Vol 6, Iss

    2021  Band 12

    Abstract: The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick–transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the ... ...

    Abstract The skin lesion erythema migrans (EM) is an initial sign of the Ixodes tick–transmitted Borreliella spirochetal infection known as Lyme disease. T cells and innate immune cells have previously been shown to predominate the EM lesion and promote the reaction. Despite the established importance of B cells and antibodies in preventing infection, the role of B cells in the skin immune response to Borreliella is unknown. Here, we used single-cell RNA-Seq in conjunction with B cell receptor (BCR) sequencing to immunophenotype EM lesions and their associated B cells and BCR repertoires. We found that B cells were more abundant in EM in comparison with autologous uninvolved skin; many were clonally expanded and had circulating relatives. EM-associated B cells upregulated the expression of MHC class II genes and exhibited preferential IgM isotype usage. A subset also exhibited low levels of somatic hypermutation despite a gene expression profile consistent with memory B cells. Our study demonstrates that single-cell gene expression with paired BCR sequencing can be used to interrogate the sparse B cell populations in human skin and reveals that B cells in the skin infection site in early Lyme disease expressed a phenotype consistent with local antigen presentation and antibody production.
    Schlagwörter Immunology ; Infectious disease ; Medicine ; R
    Sprache Englisch
    Erscheinungsdatum 2021-06-01T00:00:00Z
    Verlag American Society for Clinical investigation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  4. Artikel ; Online: Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination

    Hiromitsu Asashima / Dongjoo Kim / Kaicheng Wang / Nikhil Lele / Nicholas C. Buitrago-Pocasangre / Rachel Lutz / Isabella Cruz / Khadir Raddassi / William E. Ruff / Michael K. Racke / JoDell E. Wilson / Tara S. Givens / Alba Grifoni / Daniela Weiskopf / Alessandro Sette / Steven H. Kleinstein / Ruth R. Montgomery / Albert C. Shaw / Fangyong Li /
    Rong Fan / David A. Hafler / Mary M. Tomayko / Erin E. Longbrake

    JCI Insight, Vol 8, Iss

    2023  Band 16

    Abstract: BACKGROUND While B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important ... ...

    Abstract BACKGROUND While B cell depletion is associated with attenuated antibody responses to SARS-CoV-2 mRNA vaccination, responses vary among individuals. Thus, elucidating the factors that affect immune responses after repeated vaccination is an important clinical need.METHODS We evaluated the quality and magnitude of the T cell, B cell, antibody, and cytokine responses to a third dose of BNT162b2 or mRNA-1273 mRNA vaccine in patients with B cell depletion.RESULTS In contrast with control individuals (n = 10), most patients on anti-CD20 therapy (n = 48) did not demonstrate an increase in spike-specific B cells or antibodies after a third dose of vaccine. A third vaccine elicited significantly increased frequencies of spike-specific non-naive T cells. A small subset of B cell–depleted individuals effectively produced spike-specific antibodies, and logistic regression models identified time since last anti-CD20 treatment and lower cumulative exposure to anti-CD20 mAbs as predictors of those having a serologic response. B cell–depleted patients who mounted an antibody response to 3 vaccine doses had persistent humoral immunity 6 months later.CONCLUSION These results demonstrate that serial vaccination strategies can be effective for a subset of B cell–depleted patients.FUNDING The NIH (R25 NS079193, P01 AI073748, U24 AI11867, R01 AI22220, UM 1HG009390, P01 AI039671, P50 CA121974, R01 CA227473, U01CA260507, 75N93019C00065, K24 AG042489), NIH HIPC Consortium (U19 AI089992), the National Multiple Sclerosis Society (CA 1061-A-18, RG-1802-30153), the Nancy Taylor Foundation for Chronic Diseases, Erase MS, the Robert Leet and Clara Guthrie Patterson Trust, and the Claude D. Pepper Older Americans Independence Center at Yale (P30 AG21342).
    Schlagwörter Autoimmunity ; COVID-19 ; Medicine ; R
    Thema/Rubrik (Code) 610 ; 616
    Sprache Englisch
    Erscheinungsdatum 2023-09-01T00:00:00Z
    Verlag American Society for Clinical investigation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  5. Artikel ; Online: West Nile Virus Seroprevalence, Connecticut, USA, 2000–2014

    Megan E. Cahill / Yi Yao / David Nock / Philip M. Armstrong / Theodore G. Andreadis / Maria A. Diuk-Wasser / Ruth R. Montgomery

    Emerging Infectious Diseases, Vol 23, Iss 4, Pp 708-

    2017  Band 710

    Abstract: West Nile virus (WNV) infection is mainly asymptomatic but can be severe in elderly persons. As part of studies on immunity and aging in Connecticut, USA, we detected WNV seroconversion in 8.5% of nonimmunosuppressed and 16.8% of immunosuppressed persons. ...

    Abstract West Nile virus (WNV) infection is mainly asymptomatic but can be severe in elderly persons. As part of studies on immunity and aging in Connecticut, USA, we detected WNV seroconversion in 8.5% of nonimmunosuppressed and 16.8% of immunosuppressed persons. Age was not a significant seroconversion factor. Our findings suggest that immune factors affect seroconversion.
    Schlagwörter West Nile virus ; aging ; immune response ; seroconversion ; viral susceptibility ; viruses ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Sprache Englisch
    Erscheinungsdatum 2017-04-01T00:00:00Z
    Verlag Centers for Disease Control and Prevention
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  6. Artikel ; Online: Early cellular and molecular signatures correlate with severity of West Nile virus infection

    Ho-Joon Lee / Yujiao Zhao / Ira Fleming / Sameet Mehta / Xiaomei Wang / Brent Vander Wyk / Shannon E. Ronca / Heather Kang / Chih-Hung Chou / Benoit Fatou / Kinga K. Smolen / Ofer Levy / Clary B. Clish / Ramnik J. Xavier / Hanno Steen / David A. Hafler / J. Christopher Love / Alex K. Shalek / Leying Guan /
    Kristy O. Murray / Steven H. Kleinstein / Ruth R. Montgomery

    iScience, Vol 26, Iss 12, Pp 108387- (2023)

    2023  

    Abstract: Summary: Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed ...

    Abstract Summary: Infection with West Nile virus (WNV) drives a wide range of responses, from asymptomatic to flu-like symptoms/fever or severe cases of encephalitis and death. To identify cellular and molecular signatures distinguishing WNV severity, we employed systems profiling of peripheral blood from asymptomatic and severely ill individuals infected with WNV. We interrogated immune responses longitudinally from acute infection through convalescence employing single-cell protein and transcriptional profiling complemented with matched serum proteomics and metabolomics as well as multi-omics analysis. At the acute time point, we detected both elevation of pro-inflammatory markers in innate immune cell types and reduction of regulatory T cell activity in participants with severe infection, whereas asymptomatic donors had higher expression of genes associated with anti-inflammatory CD16+ monocytes. Therefore, we demonstrated the potential of systems immunology using multiple cell-type and cell-state-specific analyses to identify correlates of infection severity and host cellular activity contributing to an effective anti-viral response.
    Schlagwörter Virology ; Diagnostics ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2023-12-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  7. Artikel ; Online: Features of acute COVID-19 associated with post-acute sequelae of SARS-CoV-2 phenotypes

    Al Ozonoff / Naresh Doni Jayavelu / Shanshan Liu / Esther Melamed / Carly E. Milliren / Jingjing Qi / Linda N. Geng / Grace A. McComsey / Charles B. Cairns / Lindsey R. Baden / Joanna Schaenman / Albert C. Shaw / Hady Samaha / Vicki Seyfert-Margolis / Florian Krammer / Lindsey B. Rosen / Hanno Steen / Caitlin Syphurs / Ravi Dandekar /
    Casey P. Shannon / Rafick P. Sekaly / Lauren I. R. Ehrlich / David B. Corry / Farrah Kheradmand / Mark A. Atkinson / Scott C. Brakenridge / Nelson I. Agudelo Higuita / Jordan P. Metcalf / Catherine L. Hough / William B. Messer / Bali Pulendran / Kari C. Nadeau / Mark M. Davis / Ana Fernandez Sesma / Viviana Simon / Harm van Bakel / Seunghee Kim-Schulze / David A. Hafler / Ofer Levy / Monica Kraft / Chris Bime / Elias K. Haddad / Carolyn S. Calfee / David J. Erle / Charles R. Langelier / Walter Eckalbar / Steven E. Bosinger / IMPACC Network / Bjoern Peters / Steven H. Kleinstein / Elaine F. Reed / Alison D. Augustine / Joann Diray-Arce / Holden T. Maecker / Matthew C. Altman / Ruth R. Montgomery / Patrice M. Becker / Nadine Rouphael

    Nature Communications, Vol 15, Iss 1, Pp 1-

    results from the IMPACC study

    2024  Band 17

    Abstract: Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. ... ...

    Abstract Abstract Post-acute sequelae of SARS-CoV-2 (PASC) is a significant public health concern. We describe Patient Reported Outcomes (PROs) on 590 participants prospectively assessed from hospital admission for COVID-19 through one year after discharge. Modeling identified 4 PRO clusters based on reported deficits (minimal, physical, mental/cognitive, and multidomain), supporting heterogenous clinical presentations in PASC, with sub-phenotypes associated with female sex and distinctive comorbidities. During the acute phase of disease, a higher respiratory SARS-CoV-2 viral burden and lower Receptor Binding Domain and Spike antibody titers were associated with both the physical predominant and the multidomain deficit clusters. A lower frequency of circulating B lymphocytes by mass cytometry (CyTOF) was observed in the multidomain deficit cluster. Circulating fibroblast growth factor 21 (FGF21) was significantly elevated in the mental/cognitive predominant and the multidomain clusters. Future efforts to link PASC to acute anti-viral host responses may help to better target treatment and prevention of PASC.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2024-01-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  8. Artikel ; Online: Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures.

    Yujiao Zhao / Matthew Amodio / Brent Vander Wyk / Bram Gerritsen / Mahesh M Kumar / David van Dijk / Kevin Moon / Xiaomei Wang / Anna Malawista / Monique M Richards / Megan E Cahill / Anita Desai / Jayasree Sivadasan / Manjunatha M Venkataswamy / Vasanthapuram Ravi / Erol Fikrig / Priti Kumar / Steven H Kleinstein / Smita Krishnaswamy /
    Ruth R Montgomery

    PLoS Neglected Tropical Diseases, Vol 14, Iss 3, p e

    2020  Band 0008112

    Abstract: The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent ...

    Abstract The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics. Furthermore, pre-existing infection may skew immune pathways or divert immune resources. We profiled immune cells from dengue virus-infected individuals by multiparameter mass cytometry (CyTOF) to define functional status. Elevations in IFNβ were noted in acute patients across the majority of cell types and were statistically elevated in 31 of 36 cell subsets. We quantified response to in vitro (re)infection with dengue or Zika viruses and detected a striking pattern of upregulation of responses to Zika infection by innate cell types which was not noted in response to dengue virus. Significance was discovered by statistical analysis as well as a neural network-based clustering approach which identified unusual cell subsets overlooked by conventional manual gating. Of public health importance, patient cells showed significant enrichment of innate cell responses to Zika virus indicating an intact and robust anti-Zika response despite the concurrent dengue infection.
    Schlagwörter Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
    Sprache Englisch
    Erscheinungsdatum 2020-03-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

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  9. Artikel ; Online: The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection.

    Yi Yao / Dara M Strauss-Albee / Julian Q Zhou / Anna Malawista / Melissa N Garcia / Kristy O Murray / Catherine A Blish / Ruth R Montgomery

    PLoS ONE, Vol 12, Iss 2, p e

    2017  Band 0172625

    Abstract: West Nile virus (WNV) typically leads to asymptomatic infection but can cause severe neuroinvasive disease or death, particularly in the elderly. Innate NK cells play a critical role in antiviral defenses, yet their role in human WNV infection is poorly ... ...

    Abstract West Nile virus (WNV) typically leads to asymptomatic infection but can cause severe neuroinvasive disease or death, particularly in the elderly. Innate NK cells play a critical role in antiviral defenses, yet their role in human WNV infection is poorly defined. Here we demonstrate that NK cells mount a robust, polyfunctional response to WNV characterized by cytolytic activity, cytokine and chemokine secretion. This is associated with downregulation of activating NK cell receptors and upregulation of NK cell activating ligands for NKG2D. The NK cell response did not differ between young and old WNV-naïve subjects, but a history of symptomatic infection is associated with more IFN-γ producing NK cell subsets and a significant decline in a specific NK cell subset. This NK repertoire skewing could either contribute to or follow heightened immune pathogenesis from WNV infection, and suggests that NK cells could play an important role in WNV infection in humans.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 616
    Sprache Englisch
    Erscheinungsdatum 2017-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
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  10. Artikel ; Online: Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes.

    Neal G Ravindra / Mia Madel Alfajaro / Victor Gasque / Nicholas C Huston / Han Wan / Klara Szigeti-Buck / Yuki Yasumoto / Allison M Greaney / Victoria Habet / Ryan D Chow / Jennifer S Chen / Jin Wei / Renata B Filler / Bao Wang / Guilin Wang / Laura E Niklason / Ruth R Montgomery / Stephanie C Eisenbarth / Sidi Chen /
    Adam Williams / Akiko Iwasaki / Tamas L Horvath / Ellen F Foxman / Richard W Pierce / Anna Marie Pyle / David van Dijk / Craig B Wilen

    PLoS Biology, Vol 19, Iss 3, p e

    2021  Band 3001143

    Abstract: There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) ... ...

    Abstract There are currently limited Food and Drug Administration (FDA)-approved drugs and vaccines for the treatment or prevention of Coronavirus Disease 2019 (COVID-19). Enhanced understanding of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and pathogenesis is critical for the development of therapeutics. To provide insight into viral replication, cell tropism, and host-viral interactions of SARS-CoV-2, we performed single-cell (sc) RNA sequencing (RNA-seq) of experimentally infected human bronchial epithelial cells (HBECs) in air-liquid interface (ALI) cultures over a time course. This revealed novel polyadenylated viral transcripts and highlighted ciliated cells as a major target at the onset of infection, which we confirmed by electron and immunofluorescence microscopy. Over the course of infection, the cell tropism of SARS-CoV-2 expands to other epithelial cell types including basal and club cells. Infection induces cell-intrinsic expression of type I and type III interferons (IFNs) and interleukin (IL)-6 but not IL-1. This results in expression of interferon-stimulated genes (ISGs) in both infected and bystander cells. This provides a detailed characterization of genes, cell types, and cell state changes associated with SARS-CoV-2 infection in the human airway.
    Schlagwörter Biology (General) ; QH301-705.5
    Sprache Englisch
    Erscheinungsdatum 2021-03-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
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