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Dr. Dahlene Fusco
Tulane University School of Medicine, New Orleans, United States

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0 Virus
0 Dengue
0 Interferon
0 Zika
0 SARS CoV-2

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Journal article
Published: 22 July 2021 in Viruses
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Data about Zika virus infection and adverse pregnancy outcomes in Southeast Asia are scarce. We conducted an unmatched case-control study of Zika virus (ZIKV) serology in pregnant women enrolled in human immunodeficiency virus (HIV) or hepatitis B virus (HBV) perinatal prevention trials between 1997 and 2015 in Thailand. Case and control groups included women with and without adverse pregnancy outcomes. Plasma samples collected during the last trimester of pregnancy were tested for ZIKV IgG/IgM and Dengue IgG/IgM (Euroimmun, AG, Germany). Case newborn plasma samples were tested for ZIKV IgM and ZIKV RNA (Viasure, Spain). The case group included women with stillbirth (n = 22) or whose infants had microcephaly (n = 4), a head circumference below the first percentile (n = 14), neurological disorders (n = 36), or had died within 10 days after birth (n = 11). No women in the case group were positive for ZIKV IgM, and none of their live-born neonates were positive for ZIKV IgM or ZIKV RNA. The overall ZIKV IgG prevalence was 29%, 24% in the case and 34% in the control groups (Fisher’s exact test; p = 0.13), while the dengue IgG seroprevalence was 90%. Neither neonatal ZIKV infections nor ZIKV-related adverse pregnancy outcomes were observed in these women with HIV and/or HBV during the 18-year study period.

ACS Style

Nicole Ngo-Giang-Huong; Charline Leroi; Dahlene Fusco; Tim Cressey; Nantawan Wangsaeng; Nicolas Salvadori; Natedao Kongyai; Wasna Sirirungsi; Marc Lallemant; Prasert Auewarakul; Woottichai Khamduang; Gonzague Jourdain. Lack of Association between Adverse Pregnancy Outcomes and Zika Antibodies among Pregnant Women in Thailand between 1997 and 2015. Viruses 2021, 13, 1423 .

AMA Style

Nicole Ngo-Giang-Huong, Charline Leroi, Dahlene Fusco, Tim Cressey, Nantawan Wangsaeng, Nicolas Salvadori, Natedao Kongyai, Wasna Sirirungsi, Marc Lallemant, Prasert Auewarakul, Woottichai Khamduang, Gonzague Jourdain. Lack of Association between Adverse Pregnancy Outcomes and Zika Antibodies among Pregnant Women in Thailand between 1997 and 2015. Viruses. 2021; 13 (8):1423.

Chicago/Turabian Style

Nicole Ngo-Giang-Huong; Charline Leroi; Dahlene Fusco; Tim Cressey; Nantawan Wangsaeng; Nicolas Salvadori; Natedao Kongyai; Wasna Sirirungsi; Marc Lallemant; Prasert Auewarakul; Woottichai Khamduang; Gonzague Jourdain. 2021. "Lack of Association between Adverse Pregnancy Outcomes and Zika Antibodies among Pregnant Women in Thailand between 1997 and 2015." Viruses 13, no. 8: 1423.

Journal article
Published: 23 June 2021 in Viruses
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A 59-year-old male with follicular lymphoma treated by anti-CD20-mediated B-cell depletion and ablative chemotherapy was hospitalized with a COVID-19 infection. Although the patient did not develop specific humoral immunity, he had a mild clinical course overall. The failure of all therapeutic options allowed infection to persist nearly 300 days with active accumulation of SARS-CoV-2 virus mutations. As a rescue therapy, an infusion of REGEN-COV (10933 and 10987) anti-spike monoclonal antibodies was performed 270 days from initial diagnosis. Due to partial clearance after the first dose (2.4 g), a consolidation dose (8 g) was infused six weeks later. Complete virus clearance could then be observed over the following month, after he was vaccinated with the Pfizer-BioNTech anti-COVID-19 vaccination. The successful management of this patient required prolonged enhanced quarantine, monitoring of virus mutations, pioneering clinical decisions based upon close consultation, and the coordination of multidisciplinary experts in virology, immunology, pharmacology, input from REGN, the FDA, the IRB, the health care team, the patient, and the patient’s family. Current decisions to take revolve around patient’s follicular lymphoma management, and monitoring for virus clearance persistence beyond disappearance of REGEN-COV monoclonal antibodies after anti-SARS-CoV-2 vaccination. Overall, specific guidelines for similar cases should be established.

ACS Style

Arnaud Drouin; Marc Theberge; Sharon Liu; Allison Smither; Shelby Flaherty; Mark Zeller; Gregory Geba; Peter Reynaud; W. Rothwell; Alfred Luk; Di Tian; Matthew Boisen; Luis Branco; Kristian Andersen; James Robinson; Robert Garry; Dahlene Fusco. Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail. Viruses 2021, 13, 1202 .

AMA Style

Arnaud Drouin, Marc Theberge, Sharon Liu, Allison Smither, Shelby Flaherty, Mark Zeller, Gregory Geba, Peter Reynaud, W. Rothwell, Alfred Luk, Di Tian, Matthew Boisen, Luis Branco, Kristian Andersen, James Robinson, Robert Garry, Dahlene Fusco. Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail. Viruses. 2021; 13 (7):1202.

Chicago/Turabian Style

Arnaud Drouin; Marc Theberge; Sharon Liu; Allison Smither; Shelby Flaherty; Mark Zeller; Gregory Geba; Peter Reynaud; W. Rothwell; Alfred Luk; Di Tian; Matthew Boisen; Luis Branco; Kristian Andersen; James Robinson; Robert Garry; Dahlene Fusco. 2021. "Successful Clearance of 300 Day SARS-CoV-2 Infection in a Subject with B-Cell Depletion Associated Prolonged (B-DEAP) COVID by REGEN-COV Anti-Spike Monoclonal Antibody Cocktail." Viruses 13, no. 7: 1202.

Journal article
Published: 02 February 2021 in Viruses
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Infections with SARS-CoV-2 can progress toward multiple clinical outcomes, and the identification of factors associated with disease severity would represent a major advance to guide care and improve prognosis. We tested for associations between SARS-CoV-2 genomic variants from an international cohort of 2508 patients and mortality rates. Findings were validated in a second cohort. Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality. Three SNPs remained associated with mortality in a generalized linear model (GLM) that also included patient age, sex, geographic region, and month of sample collection. Multiple SNPs were confirmed in the validation cohort. These SNPs represent targets to assess the mechanisms underlying COVID-19 disease severity and warrant straightforward validation in functional studies.

ACS Style

Eric Dumonteil; Dahlene Fusco; Arnaud Drouin; Claudia Herrera. Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality. Viruses 2021, 13, 227 .

AMA Style

Eric Dumonteil, Dahlene Fusco, Arnaud Drouin, Claudia Herrera. Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality. Viruses. 2021; 13 (2):227.

Chicago/Turabian Style

Eric Dumonteil; Dahlene Fusco; Arnaud Drouin; Claudia Herrera. 2021. "Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality." Viruses 13, no. 2: 227.

Journal article
Published: 30 October 2020 in Cytokine
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The developing field of osteoimmunology supports importance of an interferon (IFN) response pathway in osteoblasts. Clarifying osteoblast-IFN interactions is important because IFN is used as salvage anti-tumor therapy but systemic toxicity is high with variable clinical results. In addition, osteoblast response to systemic bursts and disruptions of IFN pathways induced by viral infection may influence bone remodeling. ZIKA virus (ZIKV) infection impacts bone development in humans and IFN response in vitro. Consistently, initial evidence of permissivity to ZIKV has been reported in human osteoblasts. Osteoblast-like Saos-2 cells are permissive to ZIKV and responsive to IFN. Multiple approaches were used to assess whether Saos-2 cells are permissive to ZIKV infection and exhibit IFN-mediated ZIKV suppression. Proteomic methods were used to evaluate impact of ZIKV and IFN on Saos-2 cells. Evidence is presented confirming Saos-2 cells are permissive to ZIKV and support IFN-mediated suppression of ZIKV. ZIKV and IFN differentially impact the Saos-2 proteome, exemplified by HELZ2 protein which is upregulated by IFN but non responsive to ZIKV. Both ZIKV and IFN suppress proteins associated with microcephaly/pseudo-TORCH syndrome (BI1, KI20A and UBP18), and ZIKV induces potential entry factor PLVAP. Transient ZIKV infection influences osteoimmune state, and IFN and ZIKV activate distinct proteomes in Saos-2 cells, which could inform therapeutic, engineered, disruptions.

ACS Style

Arnaud Drouin; Nicholas Wallbillich; Marc Theberge; Sharon Liu; Joshua Katz; Kamela Bellovoda; Scarlett Se Yun Cheon; Frederick Gootkind; Emily Bierman; Jason Zavras; Matthew J. Berberich; Marian Kalocsay; Fernando Guastaldi; Nicolas Salvadori; Maria Troulis; Dahlene N. Fusco. Impact of Zika virus on the human type I interferon osteoimmune response. Cytokine 2020, 137, 155342 .

AMA Style

Arnaud Drouin, Nicholas Wallbillich, Marc Theberge, Sharon Liu, Joshua Katz, Kamela Bellovoda, Scarlett Se Yun Cheon, Frederick Gootkind, Emily Bierman, Jason Zavras, Matthew J. Berberich, Marian Kalocsay, Fernando Guastaldi, Nicolas Salvadori, Maria Troulis, Dahlene N. Fusco. Impact of Zika virus on the human type I interferon osteoimmune response. Cytokine. 2020; 137 ():155342.

Chicago/Turabian Style

Arnaud Drouin; Nicholas Wallbillich; Marc Theberge; Sharon Liu; Joshua Katz; Kamela Bellovoda; Scarlett Se Yun Cheon; Frederick Gootkind; Emily Bierman; Jason Zavras; Matthew J. Berberich; Marian Kalocsay; Fernando Guastaldi; Nicolas Salvadori; Maria Troulis; Dahlene N. Fusco. 2020. "Impact of Zika virus on the human type I interferon osteoimmune response." Cytokine 137, no. : 155342.

Original research article
Published: 20 February 2017 in Frontiers in Microbiology
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Flaviviral infections including dengue virus are an increasing clinical problem worldwide. Dengue infection triggers host production of the type 1 IFN, IFN alpha, one of the strongest and broadest acting antivirals known. However, dengue virus subverts host IFN signaling at early steps of IFN signal transduction. This subversion allows unbridled viral replication which subsequently triggers ongoing production of IFN which, again, is subverted. Identification of downstream IFN antiviral effectors will provide targets which could be activated to restore broad acting antiviral activity, stopping the signal to produce endogenous IFN at toxic levels. To this end, we performed a targeted functional genomic screen for IFN antiviral effector genes (IEGs), identifying 56 IEGs required for antiviral effects of IFN against fully infectious dengue virus. Dengue IEGs were enriched for genes encoding nuclear receptor interacting proteins, including HELZ2, MAP2K4, SLC27A2, HSP90AA1, and HSP90AB1. We focused on HELZ2 (Helicase With Zinc Finger 2), an IFN stimulated gene and IEG which encodes a promiscuous nuclear factor coactivator that exists in two isoforms. The two unique HELZ2 isoforms are both IFN responsive, contain ISRE elements, and gene products increase in the nucleus upon IFN stimulation. Chromatin immunoprecipitation-sequencing revealed that the HELZ2 complex interacts with triglyceride-regulator LMF1. Mass spectrometry revealed that HELZ2 knockdown cells are depleted of triglyceride subsets. We thus sought to determine whether HELZ2 interacts with a nuclear receptor known to regulate immune response and lipid metabolism, AHR, and identified HELZ2:AHR interactions via co-immunoprecipitation, found that AHR is a dengue IEG, and that an AHR ligand, FICZ, exhibits anti-dengue activity. Primary bone marrow derived macrophages from HELZ2 knockout mice, compared to wild type controls, exhibit enhanced dengue infectivity. Overall, these findings reveal that IFN antiviral response is mediated by HELZ2 transcriptional upregulation, enrichment of HELZ2 protein levels in the nucleus, and activation of a transcriptional program that appears to modulate intracellular lipid state. IEGs identified in this study may serve as both (1) potential targets for host directed antiviral design, downstream of the common flaviviral subversion point, as well as (2) possible biomarkers, whose variation, natural, or iatrogenic, could affect host response to viral infections.

ACS Style

Dahlene N. Fusco; Henry Pratt; Stephen Kandilas; Se Yun Cheon; Wenyu Lin; D. Alex Cronkite; Megha Basavappa; Kate Jeffrey; Anthony Anselmo; Ruslan Sadreyev; Clarence Yapp; Xu Shi; John O'Sullivan; Robert E. Gerszten; Takuya Tomaru; Satoshi Yoshino; Tetsurou Satoh; Raymond T. Chung. HELZ2 Is an IFN Effector Mediating Suppression of Dengue Virus. Frontiers in Microbiology 2017, 8, 240 .

AMA Style

Dahlene N. Fusco, Henry Pratt, Stephen Kandilas, Se Yun Cheon, Wenyu Lin, D. Alex Cronkite, Megha Basavappa, Kate Jeffrey, Anthony Anselmo, Ruslan Sadreyev, Clarence Yapp, Xu Shi, John O'Sullivan, Robert E. Gerszten, Takuya Tomaru, Satoshi Yoshino, Tetsurou Satoh, Raymond T. Chung. HELZ2 Is an IFN Effector Mediating Suppression of Dengue Virus. Frontiers in Microbiology. 2017; 8 ():240.

Chicago/Turabian Style

Dahlene N. Fusco; Henry Pratt; Stephen Kandilas; Se Yun Cheon; Wenyu Lin; D. Alex Cronkite; Megha Basavappa; Kate Jeffrey; Anthony Anselmo; Ruslan Sadreyev; Clarence Yapp; Xu Shi; John O'Sullivan; Robert E. Gerszten; Takuya Tomaru; Satoshi Yoshino; Tetsurou Satoh; Raymond T. Chung. 2017. "HELZ2 Is an IFN Effector Mediating Suppression of Dengue Virus." Frontiers in Microbiology 8, no. : 240.