The role of the DE and EF loop of BKPyV VP1 in the serological cross-reactivity between subtypes

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00567031" target="_blank" >RIV/61388963:_____/23:00567031 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/23:10464275

Result on the web

<a href="https://doi.org/10.1016/j.virusres.2022.199031" target="_blank" >https://doi.org/10.1016/j.virusres.2022.199031</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.virusres.2022.199031" target="_blank" >10.1016/j.virusres.2022.199031</a>

Result language

angličtina

Original language name

The role of the DE and EF loop of BKPyV VP1 in the serological cross-reactivity between subtypes

Original language description

BK virus (BKPyV) is a causative agent of BKPyV-associated nephropathy and graft rejections in kidney transplant patients. It establishes persistent infection in the kidneys, which can lead to reactivation in an immunosuppressed state or transmission to kidney recipients. Complications in the case of donor-derived infections can be caused by differences between the four known BKPyV subtypes, as prior infection with one subtype does not guarantee protection against de novo infection with other subtypes. The recipient and donor pretransplant serotyping is not routinely performed since simple ELISA tests employing antigens derived from the major viral capsid protein 1 (VP1) are hindered by the high cross-reactivity of anti-VP1 antibodies against all subtypes. Identifying subtype-specific epitopes in VP1 could lead to the design of specific antigens and the improvement of serodiagnostics for kidney transplantation. We aimed to study the surface residues responsible for the interactions with the subtype-specific antibodies by focusing on the DE and EF loops of VP1, which have only a small number of distinct amino acid differences between the most common subtypes, BKPyV-I and BKPyV-IV. We designed two mutant virus-like particles (VLPs): we introduced BKPyV-I characteristic amino acid residues (either H139N in the DE loop or D175E and I178V changes in the EF loop) into the base sequence of a BKPyV-IV VP1. This way, we created BKPyV-IV mutant VLPs with the sequence of either the BKPyV-I DE loop or the BKPyV-I EF loop. These mutants were then used as competing antigens in an antigen competition assay with a panel of patient sera, and changes in antibody reactivity were assessed by ELISA. We found that the changes introduced into the BKPyV-IV VP1 EF loop restrict antibody recognition in most samples and that converting the BKPyV-IV DE loop into its BKPyV-I equivalent attracts anti-VP1 BKPyV-I antibodies. Although our results did not lead to the discovery of a subtype-specific epitope on the VP1, they suggested that the arrangement of the EF loop in VP1 might dictate the mode of interaction between virus and anti-VP1 antibodies in general and that the interactions between the antibodies and the viral capsid might be very complex. Consequently, an antigen competition assay as an assay to distinguish between BKPyV serotypes might prove difficult to interpret.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10607 - Virology

Project

<a href="/en/project/EF16_019%2F0000729" target="_blank" >EF16_019/0000729: Chemical biology for drugging undruggable targets</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Virus Research

ISSN

0168-1702

e-ISSN

1872-7492

Volume of the periodical

324

Issue of the periodical within the volume

January

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

9

Pages from-to

199031

UT code for WoS article

000919657600001

EID of the result in the Scopus database

2-s2.0-85145740835