Novel insights into the pathogenetic mechanisms of Parvovirus B19

Parvovirus B19 (B19V) is a human ssDNA virus responsible for a wide range of clinical manifestations. The diversity in pathologies associated with B19V infection suggests an underlying diversity in pathogenetic mechanisms, closely linked to the interaction of virus, biological characteristics of cell environments and the response of immune system. The development of model systems to understand these interactions is a now offering novel opportunities to understand virus-cell interactions and to develop effective antiviral strategies. Model systems used to investigate the characteristics of B19V replication, other than the widely used UT7/EpoS1 megakaryoblastoid cell line, now include the ex vivo-expanded CD36+ erythroid progenitor cells (EPCs), that demonstrated to be a highly permissive system for B19V replication and expression. Endothelial cell lines have also been recently used to study their interaction with B19V. These studies can finally take advantages on the recently acquired ability to generate fully infectious virus in cell cultures. Quantitative molecular diagnostic assays, coupled to sensitive immunoassays, can yield a very accurate definition of the course of infections in a clinical setting. Definition of the basis of selective tropism of B19V toward EPCs on the basis of novel coreceptors. Definition of the mechanistics details of B19V replication, and of its replicative cycle/expression profile. This highlights the close dependence of viral replication and generation of infectious virus on the differentiation stage within erythroid lineage, dependence of cell physiology status, such as Epo stimulation and hypoxic conditions. Effects of B19V on cell physiology, mainly deregulation of cell cycle and induction of apoptosis, that is a major determinant of transient erythroid aplasia. Relevance of ADE phenomena in the interaction of B19V with cells such as monocytic or endothelial cells, thus contributing to the necrotic or inflammatory aspects that are associated to B19V infection. Persistence of virus in tissues, possible epigenetic mechanisms. Dependence of infection outcome on innate and adaptive immune response. Possible autoimmune phenomena. Wide range of clinical manifestations and relevance of laboratory markers of infection. Advances in our knowledge and understanding of B19V replication, cell interactions and clinical manifestations bear two implications for future developments. First, an increased awareness of the clinical relevance of the virus and implementation of diagnostics algorithms. Then, the possibility to develop and test compounds with efficient antiviral activity, as an etiological approach replacing the actual supportive or symptomatic therapy.