Article ; Online: Globoside Is Dispensable for Parvovirus B19 Entry but Essential at a Postentry Step for Productive Infection.
2019 Volume 93, Issue 20
Abstract: Globoside (Gb4) is considered the primary receptor of parvovirus B19 (B19V); however, its expression does not correlate well with the attachment and restricted tropism of the virus. The N terminus of VP1 (VP1u) of B19V interacts with an as-yet-unknown ... ...
Abstract | Globoside (Gb4) is considered the primary receptor of parvovirus B19 (B19V); however, its expression does not correlate well with the attachment and restricted tropism of the virus. The N terminus of VP1 (VP1u) of B19V interacts with an as-yet-unknown receptor required for virus internalization. In contrast to Gb4, the VP1u cognate receptor is expressed exclusively in cells that B19V can internalize. With the aim of clarifying the role of Gb4 as a B19V receptor, we knocked out the gene B3GalNT1 coding for the enzyme globoside synthase in UT7/Epo cells. Consequently, B3GalNT1 transcripts and Gb4 became undetectable in the knockout (KO) cells without affecting cell viability and proliferation. Unexpectedly, virus attachment, internalization, and nuclear targeting were not disturbed in the KO cells. However, NS1 transcription failed, and consequently, genome replication and capsid protein expression were abrogated. The block could be circumvented by transfection with a B19V infectious clone, indicating that Gb4 is not required after the generation of viral double-stranded DNA with resolved inverted terminal repeats. While in wild-type (WT) cells, occupation of the VP1u cognate receptor with recombinant VP1u disturbed virus binding and blocked the infection, antibodies against Gb4 had no significant effect. In a mixed population of WT and KO cells, B19V selectively infected WT cells. This study demonstrates that Gb4 does not have the expected receptor function, as it is dispensable for virus entry; however, it is essential for productive infection, explaining the resistance of the rare individuals lacking Gb4 to B19V infection. |
---|---|
MeSH term(s) | Capsid Proteins/genetics ; Capsid Proteins/metabolism ; Cell Line ; Cells, Cultured ; Erythema Infectiosum/metabolism ; Erythema Infectiosum/virology ; Gene Knockdown Techniques ; Globosides/metabolism ; Host-Pathogen Interactions ; Humans ; Parvovirus B19, Human/physiology ; Protein Binding ; Receptors, Virus/metabolism ; Viral Nonstructural Proteins/metabolism ; Virus Internalization ; Virus Replication |
Chemical Substances | Capsid Proteins ; Globosides ; NS1 protein, parvovirus ; Receptors, Virus ; Viral Nonstructural Proteins |
Language | English |
Publishing date | 2019-09-30 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 80174-4 |
ISSN | 1098-5514 ; 0022-538X |
ISSN (online) | 1098-5514 |
ISSN | 0022-538X |
DOI | 10.1128/JVI.00972-19 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
Zs.A 609: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.