Inestigation oncellular elements involved in Parvovirus B19 infection

Fasano, Erika (2025) Inestigation oncellular elements involved in Parvovirus B19 infection, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze biotecnologiche, biocomputazionali, farmaceutiche e farmacologiche, 37 Ciclo.
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Abstract

Human Parvovirus B19 (B19V) is a ssDNA virus classified within the Erythrovirus genus of the Parvoviridae family. B19V exhibits a selective tropism for erythroid progenitor cells (EPCs) within the bone marrow. The cellular susceptibility and permissiveness to B19V may be explained by a complex combination of several factors. Regarding the expression of specific co-receptors on the surface of the target cells, the VP1u binding coreceptor (VP1u-coR) has been identified as a molecule involved in the B19V entry step. The precise impact of B19V on EPCs remains to be fully elucidated. Therefore, the objective of this study is to gain a deeper understanding of the interactions between B19V and EPCs. The phenotypic characterisation of the cells using flow cytometric analysis for erythroid surface markers and B19V coreceptor substantiates the hypothesis that the efficacy of viral replication is critically linked to the cell differentiation state. Furthermore, an enrichment of the VP1u-coR-expressing cell fraction was conducted through FACS to assess the potential role of VP1u-coR during the infectious process. The results suggest that this interaction may play a role in the later stages of infection, leading to a productive replicative cycle. mRNAseq analysis enabled the characterisation of B19V-induced effects on both the host and viral expression profiles, thereby enhancing our understanding of the pathogenic potential of this virus. The research conducted in Zahra Kadri's laboratory focused on the role of SAMHD1 as host restriction/permissiveness factors against B19V in a bank of UT7/EPO subclones with increasing graded permissiveness towards B19V. These cells were engineered using the CRISPR/Cas9 technique to knockout the SAMHD1 gene. The results obtained do not allow us to conclude whether SAMHD1 acts as a restriction or permissive factor during B19V infection. It would be beneficial to elucidate the potential correlation between SAMHD1 and B19V, which appears to be an indirect one.

Abstract
Tipologia del documento
Tesi di dottorato
Autore
Fasano, Erika
Supervisore
Dottorato di ricerca
Ciclo
37
Coordinatore
Settore disciplinare
Settore concorsuale
Parole chiave
Human Parvovirus B19; infection; Erythroid progenitor cells; cellular susceptibility and permissiveness; VP1u-coR; FACS analysis; mRNAseq analysis; SAMHD1; CRISPR/Cas9 technique
Data di discussione
25 Marzo 2025
URI

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