Cargando…

Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS

A number of studies have suggested that human herpesvirus 6A (HHV-6A) may play a role in multiple sclerosis (MS). Three possible hypotheses have been investigated: (1) U24 from HHV-6A (U24-6A) mimics myelin basic protein (MBP) through analogous phosphorylation and interaction with Fyn-SH3; (2) U24-6...

Descripción completa

Detalles Bibliográficos
Autores principales: Pi, Keng-Shuo, Bortolotti, Daria, Sang, Yurou, Schiuma, Giovanna, Beltrami, Silvia, Rizzo, Sabrina, Bortoluzzi, Alessandra, Baldi, Eleonora, Creagh, A. Louise, Haynes, Charles A., Rizzo, Roberta, Straus, Suzana K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696605/
https://www.ncbi.nlm.nih.gov/pubmed/36366483
http://dx.doi.org/10.3390/v14112384
_version_ 1784838352028041216
author Pi, Keng-Shuo
Bortolotti, Daria
Sang, Yurou
Schiuma, Giovanna
Beltrami, Silvia
Rizzo, Sabrina
Bortoluzzi, Alessandra
Baldi, Eleonora
Creagh, A. Louise
Haynes, Charles A.
Rizzo, Roberta
Straus, Suzana K.
author_facet Pi, Keng-Shuo
Bortolotti, Daria
Sang, Yurou
Schiuma, Giovanna
Beltrami, Silvia
Rizzo, Sabrina
Bortoluzzi, Alessandra
Baldi, Eleonora
Creagh, A. Louise
Haynes, Charles A.
Rizzo, Roberta
Straus, Suzana K.
author_sort Pi, Keng-Shuo
collection PubMed
description A number of studies have suggested that human herpesvirus 6A (HHV-6A) may play a role in multiple sclerosis (MS). Three possible hypotheses have been investigated: (1) U24 from HHV-6A (U24-6A) mimics myelin basic protein (MBP) through analogous phosphorylation and interaction with Fyn-SH3; (2) U24-6A affects endocytic recycling by binding human neural precursor cell (NPC) expressed developmentally down-regulated protein 4-like WW3* domain (hNedd4L-WW3*); and (3) MS patients who express Killer Cell Immunoglobulin Like Receptor 2DL2 (KIR2DL2) on natural killer (NK) cells are more susceptible to HHV-6 infection. In this contribution, we examined the validity of these propositions by investigating the interactions of U24 from HHV-6B (U24-6B), a variant less commonly linked to MS, with Fyn-SH3 and hNedd4L-WW3* using heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) titrations and isothermal titration calorimetry (ITC). In addition, the importance of phosphorylation and the specific role of U24 in NK cell activation in MS patients were examined. Overall, the findings allowed us to shed light into the models linking HHV-6 to MS and the involvement of U24.
format Online
Article
Text
id pubmed-9696605
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-96966052022-11-26 Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS Pi, Keng-Shuo Bortolotti, Daria Sang, Yurou Schiuma, Giovanna Beltrami, Silvia Rizzo, Sabrina Bortoluzzi, Alessandra Baldi, Eleonora Creagh, A. Louise Haynes, Charles A. Rizzo, Roberta Straus, Suzana K. Viruses Article A number of studies have suggested that human herpesvirus 6A (HHV-6A) may play a role in multiple sclerosis (MS). Three possible hypotheses have been investigated: (1) U24 from HHV-6A (U24-6A) mimics myelin basic protein (MBP) through analogous phosphorylation and interaction with Fyn-SH3; (2) U24-6A affects endocytic recycling by binding human neural precursor cell (NPC) expressed developmentally down-regulated protein 4-like WW3* domain (hNedd4L-WW3*); and (3) MS patients who express Killer Cell Immunoglobulin Like Receptor 2DL2 (KIR2DL2) on natural killer (NK) cells are more susceptible to HHV-6 infection. In this contribution, we examined the validity of these propositions by investigating the interactions of U24 from HHV-6B (U24-6B), a variant less commonly linked to MS, with Fyn-SH3 and hNedd4L-WW3* using heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) titrations and isothermal titration calorimetry (ITC). In addition, the importance of phosphorylation and the specific role of U24 in NK cell activation in MS patients were examined. Overall, the findings allowed us to shed light into the models linking HHV-6 to MS and the involvement of U24. MDPI 2022-10-28 /pmc/articles/PMC9696605/ /pubmed/36366483 http://dx.doi.org/10.3390/v14112384 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pi, Keng-Shuo
Bortolotti, Daria
Sang, Yurou
Schiuma, Giovanna
Beltrami, Silvia
Rizzo, Sabrina
Bortoluzzi, Alessandra
Baldi, Eleonora
Creagh, A. Louise
Haynes, Charles A.
Rizzo, Roberta
Straus, Suzana K.
Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
title Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
title_full Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
title_fullStr Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
title_full_unstemmed Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
title_short Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
title_sort studying the interactions of u24 from hhv-6 in order to further elucidate its potential role in ms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696605/
https://www.ncbi.nlm.nih.gov/pubmed/36366483
http://dx.doi.org/10.3390/v14112384
work_keys_str_mv AT pikengshuo studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT bortolottidaria studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT sangyurou studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT schiumagiovanna studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT beltramisilvia studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT rizzosabrina studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT bortoluzzialessandra studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT baldieleonora studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT creaghalouise studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT haynescharlesa studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT rizzoroberta studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms
AT straussuzanak studyingtheinteractionsofu24fromhhv6inordertofurtherelucidateitspotentialroleinms