Abstract
Parvovirus B19 (B19V) is a small non-enveloped virus and known as the causative agent for the mild childhood disease erythema infectiosum. B19V has an extraordinary narrow tissue tropism, showing only productive infection in erythroid precursor cells in the bone marrow. We recently found that the viral protein 1 unique region (VP1u) contains an N-terminal receptor-binding domain (RBD), which mediates the uptake of the virus into cells of the erythroid lineage. To further investigate the role of the RBD in connection with a B19V-unrelated capsid, we chemically coupled the VP1u of B19V to the bacteriophage MS2 capsid and tested the internalization capacity of the bioconjugate on permissive cells. In comparison, we studied the cellular uptake and infection of B19V along the erythroid differentiation. The results showed that the MS2-VP1u bioconjugate mimicked the specific internalization of the native B19V into erythroid precursor cells, which further coincides with the restricted infection profile. The successful mimicry of B19V uptake demonstrates that the RBD in the VP1u is sufficient for the endocytosis of the viral capsid. Furthermore, the recombinant VP1u competed with B19V uptake into permissive cells, thus excluding a significant alternative uptake mechanism by other receptors. Strikingly, the VP1u receptor appeared to be expressed only on erythropoietin-dependent erythroid differentiation stages that also provide the necessary intracellular factors for a productive infection. Taken together, these findings suggest that the VP1u binds to a yet-unknown erythroid-specific cellular receptor and thus restricts the virus entry to permissive cells.
Highlights
IntroductionThe transmission of the virus occurs via the respiratory route and the infection generally leads to mild courses as the childhood disease erythema infectiosum [1]
Parvovirus B19 (B19V) is a human pathogen with a worldwide prevalence
Our previous findings showed that the viral protein 1 unique region (VP1u) region of B19V binds and internalizes into erythroid precursor cells, suggesting that the virus uses the receptor-binding domain (RBD) in the VP1u for the uptake of
Summary
The transmission of the virus occurs via the respiratory route and the infection generally leads to mild courses as the childhood disease erythema infectiosum [1]. B19V infections in immunocompromised people or individuals with hemolytic disorders may become chronic and cause severe manifestations. The cellular tropism of B19V is strongly restricted to intermediate erythroid differentiation stages, where the susceptibility increases from erythroid progenitors to erythroblasts [2]. Studies using ex vivo expanded cluster of differentiation (CD) 34+ hematopoietic stem cells show the highest permissivity in erythropoietin-dependent erythroid differentiation stages—colony forming unit-erythroid (CFU-E), proerythroblasts and early basophilic erythroblasts [3,4,5,6]. The extraordinarily narrow tropism is supposed to be determined by both a restricted receptor expression and intracellular factors [7]
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