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) U24-6A 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.

Viral Proteins with PxxP and PY Motifs May Play a Role in Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating disease that arises from immune system attacks to the protective myelin sheath that covers nerve fibers and ensures optimal communication between brain and body. Although the cause of MS is unknown, a number of factors, which include viruses, have been identified as increasing the risk of displaying MS symptoms. Specifically, the ubiquitous and highly prevalent Epstein-Barr virus, human herpesvirus 6, cytomegalovirus, varicella-zoster virus, and other viruses have been identified as potential triggering agents. In this review, we examine the specific role of proline-rich proteins encoded by these viruses and their potential role in MS at a molecular level.