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Article ; Online: Viral and host factors drive a type 1 Epstein-Barr virus spontaneous lytic phenotype.

Willard, Katherine A / Barry, Ashley P / Oduor, Cliff I / Ong'echa, John Michael / Bailey, Jeffrey A / Moormann, Ann M / Luftig, Micah A

mBio

2023 , Page(s) e0220423

Abstract: Importance: Epstein-Barr virus (EBV) infects over 95% of adults worldwide. Given its connection to various cancers and autoimmune disorders, it is important to understand the mechanisms by which infection with EBV can lead to these diseases. In this ... ...

Abstract	Importance: Epstein-Barr virus (EBV) infects over 95% of adults worldwide. Given its connection to various cancers and autoimmune disorders, it is important to understand the mechanisms by which infection with EBV can lead to these diseases. In this study, we describe an unusual spontaneous lytic phenotype in EBV strains isolated from Kenyan endemic Burkitt lymphoma patients. Because lytic replication of EBV has been linked to the pathogenesis of various diseases, these data could illuminate viral and host factors involved in this process.
Language	English
Publishing date	2023-11-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.02204-23
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Article ; Online: Profiling genome-wide recombination in Epstein Barr virus reveals type-specific patterns and associations with endemic-Burkitt lymphoma

Agwati, Eddy O. / Oduor, Cliff I. / Ayieko, Cyrus / Ong’echa, John Michael / Moormann, Ann M. / Bailey, Jeffrey A.

Virol J. 2022 Dec., v. 19, no. 1 p.208-208

2022

Abstract: BACKGROUND: Endemic Burkitt lymphoma (eBL) is potentiated through the interplay of Epstein Barr virus (EBV) and holoendemic Plasmodium falciparum malaria. To better understand EBV’s biology and role in eBL, we characterized genome-wide recombination ... ...

Abstract	BACKGROUND: Endemic Burkitt lymphoma (eBL) is potentiated through the interplay of Epstein Barr virus (EBV) and holoendemic Plasmodium falciparum malaria. To better understand EBV’s biology and role in eBL, we characterized genome-wide recombination sites and patterns as a source of genetic diversity in EBV genomes in our well-defined population of eBL cases and controls from Western Kenya. METHODS: EBV genomes representing 54 eBL cases and 32 healthy children from the same geographic region in Western Kenya that we previously sequenced were analyzed. Whole-genome multiple sequence alignment, recombination analyses, and phylogenetic inference were made using multiple alignment with fast Fourier transform, recombination detection program 4, and molecular evolutionary genetics analysis. RESULTS: We identified 28 different recombination events and 71 (82.6%) of the 86 EBV genomes analyzed contained evidence of one or more recombinant segments. Associated recombination breakpoints were found to occur in a total of 42 different genes, with only 7 (16.67%) being latent genes. Recombination events were major drivers of clustering within genome-wide phylogenetic trees. The occurrence of recombination segments was comparable between genomes from male and female participants and across age groups. More recombinant segments were found in EBV type 1 genomes (p = 6.4e − 06) and the genomes from the eBLs (p = 0.037). Two recombination events were enriched in the eBLs; event 47 (OR = 4.07, p = 0.038) and event 50 (OR = 14.24, p = 0.012). CONCLUSIONS: EBV genomes have extensive evidence of recombination likely acquired progressively and cumulatively over time. Recombination patterns display a heterogeneous occurrence rate across the genome with enrichment in lytic genes. Overall, recombination appears to be a major evolutionary force impacting EBV diversity and genome structure with evidence of the association of specific recombinants with eBL.
Keywords	Human gammaherpesvirus 4 ; Plasmodium falciparum ; endemic diseases ; falciparum malaria ; females ; genetic variation ; genome ; lymphoma ; males ; phylogeny ; sequence alignment ; Kenya
Language	English
Dates of publication	2022-12
Size	p. 208.
Publishing place	BioMed Central
Document type	Article ; Online
ZDB-ID	2160640-7
ISSN	1743-422X
ISSN	1743-422X
DOI	10.1186/s12985-022-01942-8
Database	NAL-Catalogue (AGRICOLA)

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Article: Loss of developmentally derived Irf8+ macrophages promotes hyperinnervation and arrhythmia in the adult zebrafish heart.

Paquette, Shannon E / Oduor, Cliff I / Gaulke, Amy / Stefan, Sabina / Bronk, Peter / Dafonseca, Vanny / Barulin, Nikolai / Lee, Cadence / Carley, Rachel / Morrison, Alan R / Choi, Bum-Rak / Bailey, Jeffrey A / Plavicki, Jessica S

bioRxiv : the preprint server for biology

2024

Abstract: Recent developments in cardiac macrophage biology have broadened our understanding of the critical functions of macrophages in the heart. As a result, there is further interest in understanding the independent contributions of distinct subsets of ... ...

Abstract	Recent developments in cardiac macrophage biology have broadened our understanding of the critical functions of macrophages in the heart. As a result, there is further interest in understanding the independent contributions of distinct subsets of macrophage to cardiac development and function. Here, we demonstrate that genetic loss of interferon regulatory factor 8 (Irf8)-positive embryonic-derived macrophages significantly disrupts cardiac conduction, chamber function, and innervation in adult zebrafish. At 4 months post-fertilization (mpf), homozygous
Language	English
Publishing date	2024-04-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.17.589909
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Article ; Online: Profiling genome-wide recombination in Epstein Barr virus reveals type-specific patterns and associations with endemic-Burkitt lymphoma.

Agwati, Eddy O / Oduor, Cliff I / Ayieko, Cyrus / Ong'echa, John Michael / Moormann, Ann M / Bailey, Jeffrey A

Virology journal

2022 Volume 19, Issue 1, Page(s) 208

Abstract: Background: Endemic Burkitt lymphoma (eBL) is potentiated through the interplay of Epstein Barr virus (EBV) and holoendemic Plasmodium falciparum malaria. To better understand EBV's biology and role in eBL, we characterized genome-wide recombination ... ...

Abstract	Background: Endemic Burkitt lymphoma (eBL) is potentiated through the interplay of Epstein Barr virus (EBV) and holoendemic Plasmodium falciparum malaria. To better understand EBV's biology and role in eBL, we characterized genome-wide recombination sites and patterns as a source of genetic diversity in EBV genomes in our well-defined population of eBL cases and controls from Western Kenya. Methods: EBV genomes representing 54 eBL cases and 32 healthy children from the same geographic region in Western Kenya that we previously sequenced were analyzed. Whole-genome multiple sequence alignment, recombination analyses, and phylogenetic inference were made using multiple alignment with fast Fourier transform, recombination detection program 4, and molecular evolutionary genetics analysis. Results: We identified 28 different recombination events and 71 (82.6%) of the 86 EBV genomes analyzed contained evidence of one or more recombinant segments. Associated recombination breakpoints were found to occur in a total of 42 different genes, with only 7 (16.67%) being latent genes. Recombination events were major drivers of clustering within genome-wide phylogenetic trees. The occurrence of recombination segments was comparable between genomes from male and female participants and across age groups. More recombinant segments were found in EBV type 1 genomes (p = 6.4e - 06) and the genomes from the eBLs (p = 0.037). Two recombination events were enriched in the eBLs; event 47 (OR = 4.07, p = 0.038) and event 50 (OR = 14.24, p = 0.012). Conclusions: EBV genomes have extensive evidence of recombination likely acquired progressively and cumulatively over time. Recombination patterns display a heterogeneous occurrence rate across the genome with enrichment in lytic genes. Overall, recombination appears to be a major evolutionary force impacting EBV diversity and genome structure with evidence of the association of specific recombinants with eBL.
MeSH term(s)	Child ; Humans ; Burkitt Lymphoma/genetics ; Herpesvirus 4, Human/genetics ; Phylogeny ; Epstein-Barr Virus Infections ; Kenya/epidemiology
Language	English
Publishing date	2022-12-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2160640-7
ISSN	1743-422X ; 1743-422X
ISSN (online)	1743-422X
ISSN	1743-422X
DOI	10.1186/s12985-022-01942-8
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Article ; Online: Distinctive Kaposi Sarcoma-Associated Herpesvirus Serological Profile during Acute

Oluoch, Peter O / Forconi, Catherine S / Oduor, Cliff I / Ritacco, Dominic A / Akala, Hoseah M / Bailey, Jeffrey A / Juliano, Jonathan J / Ong'echa, John M / Münz, Christian / Moormann, Ann M

International journal of molecular sciences

2023 Volume 24, Issue 7

Abstract: The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) and the incidence of endemic Kaposi sarcoma (KS) overlap with regions of malaria endemicity in sub-Saharan Africa. Multiple studies have shown an increased risk of KSHV seroconversion in ... ...

Abstract	The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) and the incidence of endemic Kaposi sarcoma (KS) overlap with regions of malaria endemicity in sub-Saharan Africa. Multiple studies have shown an increased risk of KSHV seroconversion in children from high malaria compared to low malaria regions; however, the impact of acute episodes of
MeSH term(s)	Child ; Humans ; Herpesvirus 8, Human ; Seroepidemiologic Studies ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Sarcoma, Kaposi ; Malaria, Falciparum/epidemiology
Language	English
Publishing date	2023-04-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24076711
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Article: Single cell transcriptional changes across the blood stages of artemisinin resistant K13

Oduor, Cliff I / Cunningham, Clark / Rustamzade, Nazrin / Zuromski, Jenna / Chin, Deborah M / Nixon, Christian P / Kurtis, Jonathan D / Juliano, Jonathan J / Bailey, Jeffrey A

bioRxiv : the preprint server for biology

2023

Abstract: Artemisinins have been a cornerstone of malaria control, but resistance ... ...

Abstract	Artemisinins have been a cornerstone of malaria control, but resistance in
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.06.570387
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Article ; Online: Expression Microdissection for the Analysis of miRNA in a Single-Cell Type.

Jenike, Ana E / Bunkelman, Brady / Perzel Mandell, Kira A / Oduor, Cliff I / Chin, Deborah / Mair, Devin / Jenike, Katharine M / Kim, Deok-Ho / Bailey, Jeffrey A / Rafailovich, Miriam H / Rosenberg, Avi Z / Halushka, Marc K

Laboratory investigation; a journal of technical methods and pathology

2023 Volume 103, Issue 7, Page(s) 100133

Abstract: Cell-specific microRNA (miRNA) expression estimates are important in characterizing the localization of miRNA signaling within tissues. Much of these data are obtained from cultured cells, a process known to significantly alter miRNA expression levels. ... ...

Abstract	Cell-specific microRNA (miRNA) expression estimates are important in characterizing the localization of miRNA signaling within tissues. Much of these data are obtained from cultured cells, a process known to significantly alter miRNA expression levels. Thus, our knowledge of in vivo cell miRNA expression estimates is poor. We previously demonstrated expression microdissection-miRNA-sequencing (xMD-miRNA-seq) to acquire in vivo estimates, directly from formalin-fixed tissues, albeit with a limited yield. In this study, we optimized each step of the xMD process, including tissue retrieval, tissue transfer, film preparation, and RNA isolation, to increase RNA yields and ultimately show strong enrichment for in vivo miRNA expression by qPCR array. These method improvements, such as the development of a noncrosslinked ethylene vinyl acetate membrane, resulted in a 23- to 45-fold increase in miRNA yield, depending on the cell type. By qPCR, miR-200a increased by 14-fold in xMD-derived small intestine epithelial cells, with a concurrent 336-fold reduction in miR-143 relative to the matched nondissected duodenal tissue. xMD is now an optimized method to obtain robust in vivo miRNA expression estimates from cells. xMD will allow formalin-fixed tissues from surgical pathology archives to make theragnostic biomarker discoveries.
MeSH term(s)	MicroRNAs/genetics ; MicroRNAs/metabolism ; Microdissection/methods ; Epithelial Cells/metabolism ; Formaldehyde ; Gene Expression Profiling
Chemical Substances	MicroRNAs ; Formaldehyde (1HG84L3525)
Language	English
Publishing date	2023-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80178-1
ISSN	1530-0307 ; 0023-6837
ISSN (online)	1530-0307
ISSN	0023-6837
DOI	10.1016/j.labinv.2023.100133
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Article ; Online: Endemic Burkitt lymphoma avatar mouse models for exploring inter-patient tumor variation and testing targeted therapies.

Saikumar Lakshmi, Priya / Oduor, Cliff I / Forconi, Catherine S / M'Bana, Viriato / Bly, Courtney / Gerstein, Rachel M / Otieno, Juliana A / Ong'echa, John M / Münz, Christian / Luftig, Micah A / Brehm, Michael A / Bailey, Jeffrey A / Moormann, Ann M

Life science alliance

2023 Volume 6, Issue 5

Abstract: Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein-Barr virus and malaria-associated aberrant B-cell activation ... ...

Abstract	Endemic Burkitt lymphoma (BL) is a childhood cancer in sub-Saharan Africa characterized by Epstein-Barr virus and malaria-associated aberrant B-cell activation and
MeSH term(s)	Animals ; Mice ; Burkitt Lymphoma/drug therapy ; Burkitt Lymphoma/genetics ; Epstein-Barr Virus Infections/complications ; Epstein-Barr Virus Infections/genetics ; Rituximab/pharmacology ; Rituximab/therapeutic use ; Herpesvirus 4, Human/genetics ; Cell Line, Tumor ; Disease Models, Animal
Chemical Substances	Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2023-03-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2575-1077
ISSN (online)	2575-1077
DOI	10.26508/lsa.202101355
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Article ; Online: Epstein-Barr Virus Genomes Reveal Population Structure and Type 1 Association with Endemic Burkitt Lymphoma.

Kaymaz, Yasin / Oduor, Cliff I / Aydemir, Ozkan / Luftig, Micah A / Otieno, Juliana A / Ong'echa, John Michael / Bailey, Jeffrey A / Moormann, Ann M

Journal of virology

2020 Volume 94, Issue 17

Abstract: Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is distinguished by its inclusion of Epstein-Barr virus (EBV). In order to better understand the impact of EBV variation in eBL tumorigenesis, we improved viral ... ...

Abstract	Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is distinguished by its inclusion of Epstein-Barr virus (EBV). In order to better understand the impact of EBV variation in eBL tumorigenesis, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (
MeSH term(s)	Adolescent ; Burkitt Lymphoma/genetics ; Burkitt Lymphoma/virology ; Child ; Child, Preschool ; DNA, Viral ; Epstein-Barr Virus Infections/epidemiology ; Epstein-Barr Virus Infections/virology ; Epstein-Barr Virus Nuclear Antigens/genetics ; Female ; Genetic Variation ; Genome, Viral ; Genome-Wide Association Study ; Herpesvirus 4, Human/genetics ; Humans ; Infant ; Kenya/epidemiology ; Male ; Odds Ratio ; Receptor, Macrophage Colony-Stimulating Factor/genetics ; Sequence Analysis, DNA ; Viral Proteins/genetics
Chemical Substances	BARF1 protein, Human herpesvirus 4 ; DNA, Viral ; Epstein-Barr Virus Nuclear Antigens ; Viral Proteins ; Receptor, Macrophage Colony-Stimulating Factor (EC 2.7.10.1) ; EBV-encoded nuclear antigen 1 (O5GA75RST7)
Language	English
Publishing date	2020-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02007-19
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Article ; Online: A New Hope for CD56

Forconi, Catherine S / Oduor, Cliff I / Oluoch, Peter O / Ong'echa, John M / Münz, Christian / Bailey, Jeffrey A / Moormann, Ann M

Frontiers in cellular and infection microbiology

2020 Volume 10, Page(s) 162

Abstract: Natural Killer (NK) cells play an essential role in antiviral and anti-tumoral immune responses. In peripheral blood, NK cells are commonly classified into two major subsets: ... ...

Abstract	Natural Killer (NK) cells play an essential role in antiviral and anti-tumoral immune responses. In peripheral blood, NK cells are commonly classified into two major subsets: CD56
MeSH term(s)	CD56 Antigen ; Child ; Chronic Disease ; Flow Cytometry ; Humans ; Immunotherapy ; Killer Cells, Natural ; Receptors, IgG ; Signaling Lymphocytic Activation Molecule Family
Chemical Substances	CD56 Antigen ; CD84 protein, human ; Receptors, IgG ; Signaling Lymphocytic Activation Molecule Family
Language	English
Publishing date	2020-04-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2020.00162
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