PMID- 36366483 OWN - NLM STAT- MEDLINE DCOM- 20221114 LR - 20230130 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 14 IP - 11 DP - 2022 Oct 28 TI - Studying the Interactions of U24 from HHV-6 in Order to Further Elucidate Its Potential Role in MS. LID - 10.3390/v14112384 [doi] LID - 2384 AB - 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. FAU - Pi, Keng-Shuo AU - Pi KS AUID- ORCID: 0000-0003-3778-8121 AD - Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. FAU - Bortolotti, Daria AU - Bortolotti D AUID- ORCID: 0000-0003-4496-9561 AD - Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy. FAU - Sang, Yurou AU - Sang Y AD - Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. AD - Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. FAU - Schiuma, Giovanna AU - Schiuma G AUID- ORCID: 0000-0003-4652-5550 AD - Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy. FAU - Beltrami, Silvia AU - Beltrami S AD - Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy. FAU - Rizzo, Sabrina AU - Rizzo S AD - Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy. FAU - Bortoluzzi, Alessandra AU - Bortoluzzi A AD - Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliero-Universitaria S. Anna, 44121 Ferrara, Italy. FAU - Baldi, Eleonora AU - Baldi E AD - Department of Neuroscience and Rehabilitation, Division of Neurology, "Sant'Anna" University-Hospital, 44121 Ferrara, Italy. FAU - Creagh, A Louise AU - Creagh AL AD - Michael Smith Laboratories and Department of Chemical and Biological Engineering, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada. FAU - Haynes, Charles A AU - Haynes CA AD - Michael Smith Laboratories and Department of Chemical and Biological Engineering, University of British Columbia, 2185 East Mall, Vancouver, BC V6T 1Z4, Canada. FAU - Rizzo, Roberta AU - Rizzo R AUID- ORCID: 0000-0001-9507-9126 AD - Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy. FAU - Straus, Suzana K AU - Straus SK AUID- ORCID: 0000-0002-5357-8450 AD - Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221028 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 SB - IM MH - Humans MH - *Herpesvirus 6, Human/physiology MH - *Roseolovirus Infections MH - *Multiple Sclerosis MH - Phosphorylation MH - Nuclear Magnetic Resonance, Biomolecular PMC - PMC9696605 OTO - NOTNLM OT - Fyn-SH3 OT - Killer Cell Immunoglobulin Like Receptor 2DL2 OT - Nedd4L OT - Roseolovirus OT - human herpes virus OT - multiple sclerosis OT - natural killer cells OT - phosphorylation COIS- The authors declare no conflict of interest. EDAT- 2022/11/12 06:00 MHDA- 2022/11/15 06:00 PMCR- 2022/10/28 CRDT- 2022/11/11 01:56 PHST- 2022/09/20 00:00 [received] PHST- 2022/10/27 00:00 [revised] PHST- 2022/10/27 00:00 [accepted] PHST- 2022/11/11 01:56 [entrez] PHST- 2022/11/12 06:00 [pubmed] PHST- 2022/11/15 06:00 [medline] PHST- 2022/10/28 00:00 [pmc-release] AID - v14112384 [pii] AID - viruses-14-02384 [pii] AID - 10.3390/v14112384 [doi] PST - epublish SO - Viruses. 2022 Oct 28;14(11):2384. doi: 10.3390/v14112384.