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doi:10.22028/D291-36280
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 |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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viruses-14-00879.pdf | 597,59 kB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons