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...

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Published inViruses Vol. 14; no. 11; p. 2384
Main Authors 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
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 28.10.2022
MDPI
Subjects
Calorimetry
Cell activation
Ethics
Fyn protein
Fyn-SH3
Genetic aspects
Health aspects
Herpesvirus 6, Human - physiology
human herpes virus
Human herpesvirus 6
Human subjects
Humans
Killer cells
Medical research
Membrane proteins
Multiple Sclerosis
Myelin
Myelin basic protein
Natural killer cells
Nedd4L
NMR
Nuclear magnetic resonance
Nuclear Magnetic Resonance, Biomolecular
Peptides
Phosphorylation
Physiological aspects
Potassium channels (inwardly-rectifying)
Proteins
Risk factors
Roseolovirus
Roseolovirus Infections
Titration
Viral infections
Viruses
Canada
United States > US
Roseolovirus
natural killer cells
human herpes virus
multiple sclerosis
Nedd4L
Killer Cell Immunoglobulin Like Receptor 2DL2
phosphorylation
Fyn-SH3
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Abstract 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.
AbstractList 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.
Audience Academic
Author Sang, Yurou
Rizzo, Sabrina
Bortoluzzi, Alessandra
Creagh, A Louise
Haynes, Charles A
Straus, Suzana K
Bortolotti, Daria
Baldi, Eleonora
Schiuma, Giovanna
Beltrami, Silvia
Pi, Keng-Shuo
Rizzo, Roberta
AuthorAffiliation 1 Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada
4 Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna, 44121 Ferrara, Italy
6 Michael Smith Laboratories and Department of Chemical and Biological Engineering, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada
2 Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy
3 Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada
5 Department of Neuroscience and Rehabilitation, Division of Neurology, “Sant’Anna” University-Hospital, 44121 Ferrara, Italy
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Issue 11
Keywords Roseolovirus
natural killer cells
human herpes virus
multiple sclerosis
Nedd4L
Killer Cell Immunoglobulin Like Receptor 2DL2
phosphorylation
Fyn-SH3
Language English
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Snippet 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...
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StartPage 2384
SubjectTerms Calorimetry
Cell activation
Ethics
Fyn protein
Fyn-SH3
Genetic aspects
Health aspects
Herpesvirus 6, Human - physiology
human herpes virus
Human herpesvirus 6
Human subjects
Humans
Killer cells
Medical research
Membrane proteins
Multiple Sclerosis
Myelin
Myelin basic protein
Natural killer cells
Nedd4L
NMR
Nuclear magnetic resonance
Nuclear Magnetic Resonance, Biomolecular
Peptides
Phosphorylation
Physiological aspects
Potassium channels (inwardly-rectifying)
Proteins
Risk factors
Roseolovirus
Roseolovirus Infections
Titration
Viral infections
Viruses
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Title Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS
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Volume 14
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