• Parvovirus B19: Virus-Cell Interactions, Pathogenetic Mechanisms and Development of Compounds with Antiviral Activity

Bua, Gloria

Subject

MED/07 Microbiologia e microbiologia clinica

Description

The pathogenic Parvovirus B19 is characterized by a strict adaptation to erythroid progenitor cells (EPCs), a heterogeneous population of differentiating cells. The aim of the work was the characterization of B19V infection dynamics in EPCs in dependence on the cell differentiation stage, in terms of distribution of infected cells, synthesis of viral nucleic acids and production of infectious virus. EPCs at early differentiation stage led to an abortive infection, without viral replication. EPCs at later stages were permissive, with highest levels of viral replicative activity at day 9 and lower levels at day 18. Quantitation of total RNA indicated a close association of genome replication and transcription with viral RNA accumulation within infected cells related to viral DNA increase during the course of infection. Analysis of the different classes of mRNAs revealed two distinct pattern of genome expression profile with a fine regulation in the frequency utilization of RNA processing signals: an early phase, when cleavage at the proximal site leading to a higher relative production of mRNA for NS protein, and a late phase, when cleavage at the distal site was more frequent leading to higher relative abundance of mRNA for VP and 11 kDA proteins. Infectious virus was released from cells at day 6–15, but not at day 18. Results providing a detailed description of B19V replication and expression profile in differentiating EPCs, highlight the very tight adaptation of B19V to a specific cellular target defined both by its erythroid lineage and its differentiation stage. This cell system provide also a reference framework to identify potential antiviral drugs active against B19V. The inhibitory activity of Cidofovir was evaluated in differentiated EPCs and UT7/EpoS1 cells and results are the first evidence of an inhibitory activity of a drug against B19V.

Date

2016-05-03

Type

Tesi di dottorato

NonPeerReviewed

Format

application/pdf

Identifier

urn:nbn:it:unibo-18834

Bua, Gloria (2016) Parvovirus B19: Virus-Cell Interactions, Pathogenetic Mechanisms and Development of Compounds with Antiviral Activity, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Scienze biochimiche e biotecnologiche , 28 Ciclo. DOI 10.6092/unibo/amsdottorato/7624.

Relations