The VP1u Receptor Restricts Parvovirus B19 Uptake to Permissive Erythroid Cells

Leisi, Remo; von Nordheim, Marcus; Ros, Carlos; Kempf, Christoph (2016). The VP1u Receptor Restricts Parvovirus B19 Uptake to Permissive Erythroid Cells. Viruses, 8(10), p. 265. Molecular Diversity Preservation International MDPI 10.3390/v8100265

[img]
Preview
Text
viruses-08-00265-v2.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry
08 Faculty of Science > Other Institutions > Teaching Staff, Faculty of Science

UniBE Contributor:

Leisi, Remo; von Nordheim, Marcus; Ros, Carlos and Kempf, Christoph

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

1999-4915

Publisher:

Molecular Diversity Preservation International MDPI

Language:

English

Submitter:

Christoph Kempf

Date Deposited:

19 Jan 2017 16:36

Last Modified:

16 Feb 2018 12:17

Publisher DOI:

10.3390/v8100265

PubMed ID:

27690083

BORIS DOI:

10.7892/boris.91749

URI:

https://boris.unibe.ch/id/eprint/91749

Actions (login required)

Edit item Edit item
Provide Feedback