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Article: Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4

Itell, Hannah L / Humes, Daryl / Overbaugh, Julie

bioRxiv : the preprint server for biology

2023

Abstract: Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, ... ...

Abstract	Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.07.527545
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Article ; Online: Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4

Itell, Hannah L / Humes, Daryl / Overbaugh, Julie

Cell reports

2023 Volume 42, Issue 6, Page(s) 112556

Abstract	Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4
MeSH term(s)	Humans ; Interferon Type I ; HIV-1/genetics ; HIV Infections/metabolism ; Cell Line ; HIV Seropositivity ; CD4-Positive T-Lymphocytes/metabolism
Chemical Substances	Interferon Type I
Language	English
Publishing date	2023-05-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2023.112556
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Host cell glycosylation selects for infection with CCR5- versus CXCR4-tropic HIV-1.

Itell, Hannah L / Humes, Daryl / Baumgarten, Nell E / Overbaugh, Julie

bioRxiv : the preprint server for biology

2023

Abstract: HIV-1 infection involves a selection bottleneck that leads to transmission of one or a few HIV variants, which nearly always use CCR5 as the coreceptor (R5 viruses) for viral entry as opposed to CXCR4 (X4 viruses). The host properties that drive this ... ...

Abstract	HIV-1 infection involves a selection bottleneck that leads to transmission of one or a few HIV variants, which nearly always use CCR5 as the coreceptor (R5 viruses) for viral entry as opposed to CXCR4 (X4 viruses). The host properties that drive this selection are not well understood and may hold keys to factors that govern HIV susceptibility. In this report, we identified SLC35A2, a transporter of UDP-galactose, as a candidate X4-specific restriction factor in CRISPR-knockout screens in primary target CD4
Language	English
Publishing date	2023-09-05
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.05.556399
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Article ; Online: Systemic and mucosal levels of lactoferrin in very low birth weight infants supplemented with bovine lactoferrin.

Itell, Hannah L / Berenz, Andrew / Mangan, Riley J / Permar, Sallie R / Kaufman, David A

Biochemistry and cell biology = Biochimie et biologie cellulaire

2020 Volume 99, Issue 1, Page(s) 25–34

Abstract: Lactoferrin supplementation may help prevent infections in preterm infants, but the efficacy has varied with different doses and products. We assessed the absorption and excretion of bovine lactoferrin (bLF) in 31 infants receiving 100, 200, or 300 mg· ... ...

Abstract	Lactoferrin supplementation may help prevent infections in preterm infants, but the efficacy has varied with different doses and products. We assessed the absorption and excretion of bovine lactoferrin (bLF) in 31 infants receiving 100, 200, or 300 mg·kg
MeSH term(s)	Animals ; Cattle ; Dietary Supplements ; Enteral Nutrition ; Enzyme-Linked Immunosorbent Assay ; Gastric Mucosa/chemistry ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Lactoferrin/administration & dosage ; Lactoferrin/analysis ; Lactoferrin/metabolism ; Milk, Human
Chemical Substances	Lactoferrin (EC 3.4.21.-)
Language	English
Publishing date	2020-08-25
Publishing country	Canada
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	54104-7
ISSN	1208-6002 ; 0829-8211
ISSN (online)	1208-6002
ISSN	0829-8211
DOI	10.1139/bcb-2020-0238
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Article ; Online: Maternal immune correlates of protection against placental transmission of cytomegalovirus.

Itell, Hannah L / Nelson, Cody S / Martinez, David R / Permar, Sallie R

Placenta

2017 Volume 60 Suppl 1, Page(s) S73–S79

Abstract: Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. In a subset of infected infants, congenital HCMV causes severe, long-lasting sequelae, including deafness, ... ...

Abstract	Human cytomegalovirus (HCMV) is the most common congenitally transmitted pathogen worldwide, impacting an estimated 1 million newborns annually. In a subset of infected infants, congenital HCMV causes severe, long-lasting sequelae, including deafness, microcephaly, neurodevelopmental delay, and even death. Accordingly, a maternal vaccine to prevent congenital HCMV infection continues to be a top public health priority. Nevertheless, all vaccines tested to date have failed to meet clinical trial endpoints. Maternal immunity provides partial protection against congenital HCMV transmission, as vertical transmission from seropositive mothers is relatively rare. Therefore, an understanding of the maternal immune correlates of protection against HCMV congenital infection will be critical to inform design of an efficacious maternal vaccine. This review summarizes our understanding of the innate and adaptive immune correlates of protection against congenital transmission of HCMV, and discusses the advantages and applications of a novel nonhuman primate model of congenital CMV transmission to aid in rational vaccine design and evaluation.
MeSH term(s)	Adaptive Immunity ; Animals ; Biomedical Research/methods ; Biomedical Research/trends ; Cytomegalovirus/immunology ; Cytomegalovirus/isolation & purification ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/congenital ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/prevention & control ; Cytomegalovirus Infections/transmission ; Cytomegalovirus Vaccines/therapeutic use ; Disease Models, Animal ; Female ; Humans ; Immunity, Cellular ; Immunity, Innate ; Macaca mulatta ; Maternal-Fetal Exchange ; Placenta/immunology ; Placenta/virology ; Pregnancy ; Pregnancy Complications, Infectious/immunology ; Pregnancy Complications, Infectious/virology
Chemical Substances	Cytomegalovirus Vaccines
Language	English
Publishing date	2017-04-20
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	603951-0
ISSN	1532-3102 ; 0143-4004
ISSN (online)	1532-3102
ISSN	0143-4004
DOI	10.1016/j.placenta.2017.04.011
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Article ; Online: Breast Milk and Saliva for Postnatal Cyto†megalovirus Screening among Very Low Birth Weight Infants.

Mukhopadhyay, Sagori / Itell, Hannah L / Hartman, Erica / Woodford, Emily / Dhudasia, Miren B / Steppe, Justin T / Valencia, Sarah / Roark, Hunter / Wade, Kelly C / Weimer, Kristin E D / Permar, Sallie R / Puopolo, Karen M

The Pediatric infectious disease journal

2022 Volume 41, Issue 11, Page(s) 904–910

Abstract: Background: The optimal approach to managing postnatal cytomegalovirus disease (pCMV) among very low birth weight (VLBW) infants remains unknown. Methods to facilitate screening are needed.: Objective: Determine whether mother's milk and infant ... ...

Abstract	Background: The optimal approach to managing postnatal cytomegalovirus disease (pCMV) among very low birth weight (VLBW) infants remains unknown. Methods to facilitate screening are needed. Objective: Determine whether mother's milk and infant saliva can be used to reliably identify maternal cytomegalovirus (CMV) serostatus and detect infant pCMV acquisition. Methods: This was a single-center, prospective cohort study of VLBW infants, and their mothers, born between 2017 and 2020. Maternal milk samples were tested for CMV immunoglobulin G (IgG) using a CMV glycoprotein B binding enzyme-linked immunosorbent assay and the results were compared with maternal serum CMV IgG results. Biweekly paired saliva and urine samples were collected from infants born to mothers with positive or unknown CMV serostatus. Saliva samples were tested for CMV DNA by quantitative real-time polymerase chain reaction (PCR) and compared with urine CMV qualitative PCR results obtained from a clinical laboratory. Results: Among 108 infants without congenital CMV included in the study, 10 (9%) acquired pCMV. Both milk and blood CMV serology results were available for 70 mothers. Maternal milk antibody testing had a sensitivity of 97.2% (95% CI: 85.5-99.9%) and specificity of 91.2% (95% CI: 76.3-98.1%) in establishing CMV serostatus. Paired serially collected saliva and urine samples (n = 203) were available for 66 infants. Saliva PCR had a sensitivity of 30.0% (95% CI: 6.7-65.2%) and specificity of 92.7% (95% CI: 88.1-96.0%) in detecting pCMV acquisition. Conclusions: Maternal breast milk is a reliable alternative sample to determine CMV serostatus. Serial testing of infant saliva was not adequately sensitive for identifying pCMV acquisition in preterm infants.
MeSH term(s)	Cytomegalovirus/genetics ; Cytomegalovirus Infections/diagnosis ; DNA, Viral/analysis ; Female ; Humans ; Immunoglobulin G ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Milk, Human ; Prospective Studies ; Real-Time Polymerase Chain Reaction
Chemical Substances	DNA, Viral ; Immunoglobulin G
Language	English
Publishing date	2022-08-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	392481-6
ISSN	1532-0987 ; 0891-3668
ISSN (online)	1532-0987
ISSN	0891-3668
DOI	10.1097/INF.0000000000003671
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Article ; Online: Phage-DMS: A Comprehensive Method for Fine Mapping of Antibody Epitopes.

Garrett, Meghan E / Itell, Hannah L / Crawford, Katharine H D / Basom, Ryan / Bloom, Jesse D / Overbaugh, Julie

iScience

2020 Volume 23, Issue 10, Page(s) 101622

Abstract: Understanding the antibody response is critical to developing vaccine and antibody-based therapies and has inspired the recent development of new methods to isolate antibodies. Methods to define the antibody-antigen interactions that determine ... ...

Abstract	Understanding the antibody response is critical to developing vaccine and antibody-based therapies and has inspired the recent development of new methods to isolate antibodies. Methods to define the antibody-antigen interactions that determine specificity or allow escape have not kept pace. We developed Phage-DMS, a method that combines two powerful approaches-immunoprecipitation of phage peptide libraries and deep mutational scanning (DMS)-to enable high-throughput fine mapping of antibody epitopes. As an example, we designed sequences encoding all possible amino acid variants of HIV Envelope to create phage libraries. Using Phage-DMS, we identified sites of escape predicted using other approaches for four well-characterized HIV monoclonal antibodies with known linear epitopes. In some cases, the results of Phage-DMS refined the epitope beyond what was determined in previous studies. This method has the potential to rapidly and comprehensively screen many antibodies in a single experiment to define sites essential for binding interactions.
Language	English
Publishing date	2020-09-29
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.101622
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Article ; Online: Dose escalation study of bovine lactoferrin in preterm infants: getting the dose right.

Kaufman, David A / Berenz, Andrew / Itell, Hannah L / Conaway, Mark / Blackman, Amy / Nataro, James P / Permar, Sallie R

Biochemistry and cell biology = Biochimie et biologie cellulaire

2020 Volume 99, Issue 1, Page(s) 7–13

Abstract: Lactoferrin as a nutritional enteral supplement has emerged as a novel preventative therapy against serious infections in preterm infants, although neonatal studies have demonstrated variable results, in part due to the lack of pharmacokinetic data and ... ...

Abstract	Lactoferrin as a nutritional enteral supplement has emerged as a novel preventative therapy against serious infections in preterm infants, although neonatal studies have demonstrated variable results, in part due to the lack of pharmacokinetic data and differences in the products tested. We conducted a prospective, dose escalation (100, 200, and 300 mg·kg
MeSH term(s)	Animals ; Birth Weight ; Cattle ; Dietary Supplements ; Enterocolitis, Necrotizing/prevention & control ; Humans ; Infant, Newborn ; Infant, Premature ; Lactoferrin/administration & dosage ; Prospective Studies ; Urinary Tract Infections/prevention & control
Chemical Substances	Lactoferrin (EC 3.4.21.-)
Language	English
Publishing date	2020-08-26
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	54104-7
ISSN	1208-6002 ; 0829-8211
ISSN (online)	1208-6002
ISSN	0829-8211
DOI	10.1139/bcb-2020-0217
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Article ; Online: Natural history of postnatal rhesus cytomegalovirus shedding by dams and acquisition by infant rhesus monkeys.

Kaur, Amitinder / Itell, Hannah L / Ehlinger, E Peek / Varner, Valerie / Gantt, Soren / Permar, Sallie R

PloS one

2018 Volume 13, Issue 10, Page(s) e0206330

Abstract: Background: Human infants frequently acquire human cytomegalovirus (HCMV) through breastfeeding, resulting in persistent high-level viral shedding in saliva and urine and infectivity to others, including pregnant women. Thus, vaccination to interrupt ... ...

Abstract	Background: Human infants frequently acquire human cytomegalovirus (HCMV) through breastfeeding, resulting in persistent high-level viral shedding in saliva and urine and infectivity to others, including pregnant women. Thus, vaccination to interrupt postnatal HCMV transmission is an attractive strategy to prevent HCMV spread and congenital infection. Rhesus CMV (RhCMV) in nonhuman primates is a valuable model for the study of immune strategies to prevent CMV transmission. Although rhesus monkeys typically acquire RhCMV before 1 year of age, the timing and mode of natural infant RhCMV transmission remain unknown. Methods: We followed 5 RhCMV-seropositive dams and their infants from birth until weaning, approximately 6 months later. RhCMV DNA levels in plasma, breast milk, saliva, and urine were measured every 2 weeks by quantitative PCR. RhCMV-specific T cell responses in peripheral blood and breast milk were measured by interferon gamma ELISpot assays. Serum IgG antibody levels were measured by ELISA. Results: Four of five postpartum RhCMV-seropositive mothers had intermittent, low-level RhCMV shedding in breast milk, whereas all had high-magnitude RhCMV shedding in saliva and urine. The kinetics of maternal blood RhCMV-specific T cell responses and viral shedding in urine and saliva did not strongly associate, though dams with consistently high systemic RhCMV-specific T cell responses tended to have undetectable RhCMV shedding in breast milk. All RhCMV-exposed infants had intermittent, low-level RhCMV shedding in saliva during the lactation period, with minimal systemic RhCMV-specific T cell responses. Conclusions: Despite exposure to RhCMV shedding in breast milk and other maternal fluids, postnatal mother-to-child RhCMV transmission appears to be less efficient than that of HCMV. A greater understanding of the determinants of RhCMV transmission and its usefulness as a model of HCMV mucosal acquisition may provide insight into strategies to prevent HCMV infections in humans.
MeSH term(s)	Animals ; Cytomegalovirus/physiology ; Cytomegalovirus Infections/immunology ; Cytomegalovirus Infections/transmission ; DNA, Viral/analysis ; DNA, Viral/blood ; DNA, Viral/urine ; Longitudinal Studies ; Macaca mulatta/immunology ; Macaca mulatta/virology ; Milk/virology ; Saliva/virology ; Virus Shedding
Chemical Substances	DNA, Viral
Language	English
Publishing date	2018-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0206330
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Article: High-resolution profiling of pathways of escape for SARS-CoV-2 spike-binding antibodies

Garrett, Meghan E / Galloway, Jared / Chu, Helen Y / Itell, Hannah L / Stoddard, Caitlin I / Wolf, Caitlin R / Logue, Jennifer K / McDonald, Dylan / Weight, Haidyn / Matsen, Frederick A / Overbaugh, Julie

Cell. 2021 May 27, v. 184, no. 11

2021

Abstract: Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be ... ...

Abstract	Defining long-term protective immunity to SARS-CoV-2 is one of the most pressing questions of our time and will require a detailed understanding of potential ways this virus can evolve to escape immune protection. Immune protection will most likely be mediated by antibodies that bind to the viral entry protein, spike (S). Here, we used Phage-DMS, an approach that comprehensively interrogates the effect of all possible mutations on binding to a protein of interest, to define the profile of antibody escape to the SARS-CoV-2 S protein using coronavirus disease 2019 (COVID-19) convalescent plasma. Antibody binding was common in two regions, the fusion peptide and the linker region upstream of the heptad repeat region 2. However, escape mutations were variable within these immunodominant regions. There was also individual variation in less commonly targeted epitopes. This study provides a granular view of potential antibody escape pathways and suggests there will be individual variation in antibody-mediated virus evolution.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; antibodies ; evolution ; immunity ; peptides ; viruses
Language	English
Dates of publication	2021-0527
Size	p. 2927-2938.e11.
Publishing place	Elsevier Inc.
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2021.04.045
Database	NAL-Catalogue (AGRICOLA)

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