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Titel: Genetic Associations and Differential mRNA Expression Levels of Host Genes Suggest a Viral Trigger for Endemic Pemphigus Foliaceus
VerfasserIn: Hoch, Valéria Bumiller-Bini
Kohler, Ana Flávia
Augusto, Danillo G.
Lobo-Alves, Sara Cristina
Malheiros, Danielle
Cipolla, Gabriel Adelman
Boldt, Angelica Beate Winter
Braun-Prado, Karin
Wittig, Michael
Franke, Andre
Pföhler, Claudia
Worm, Margitta
van Beek, Nina
Goebeler, Matthias
Sárdy, Miklós
Ibrahim, Saleh
Busch, Hauke
Schmidt, Enno
Hundt, Jennifer Elisabeth
Araujo-Souza, Patrícia Savio de
Petzl-Erler, Maria Luiza
Sprache: Englisch
Titel: Viruses
Bandnummer: 14
Heft: 5
Verlag/Plattform: MDPI
Erscheinungsjahr: 2022
Freie Schlagwörter: endemic pemphigus foliaceus
virus
genetic association
differential gene expression
autoimmune disease
environmental factors
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: The long search for the environmental trigger of the endemic pemphigus foliaceus (EPF, fogo selvagem) has not yet resulted in any tangible findings. Here, we searched for genetic asso ciations and the differential expression of host genes involved in early viral infections and innate antiviral defense. Genetic variants could alter the structure, expression sites, or levels of the gene products, impacting their functions. By analyzing 3063 variants of 166 candidate genes in 227 EPF patients and 194 controls, we found 12 variants within 11 genes associated with differential suscepti bility (p < 0.005) to EPF. The products of genes TRIM5, TPCN2, EIF4E, EIF4E3, NUP37, NUP50, NUP88, TPR, USP15, IRF8, and JAK1 are involved in different mechanisms of viral control, for example, the regulation of viral entry into the host cell or recognition of viral nucleic acids and proteins. Only two of nine variants were also associated in an independent German cohort of sporadic PF (75 patients, 150 controls), aligning with our hypothesis that antiviral host genes play a major role in EPF due to a specific virus–human interaction in the endemic region. Moreover, CCL5, P4HB, and APOBEC3G mRNA levels were increased (p < 0.001) in CD4+ T lymphocytes of EPF patients. Because there is limited or no evidence that these genes are involved in autoimmunity, their crucial role in antiviral responses and the associations that we observed support the hypothesis of a viral trigger for EPF, presumably a still unnoticed flavivirus. This work opens new frontiers in searching for the trigger of EPF, with the potential to advance translational research that aims for disease prevention and treatment.
DOI der Erstveröffentlichung: 10.3390/v14050879
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-362800
hdl:20.500.11880/32962
http://dx.doi.org/10.22028/D291-36280
ISSN: 1999-4915
Datum des Eintrags: 30-Mai-2022
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Materials
In Beziehung stehendes Objekt: https://www.mdpi.com/article/10.3390/v14050879/s1
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Dermatologie
Professur: M - Keiner Professur zugeordnet
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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