ABSTRACT
[This corrects the article DOI: 10.3389/fmicb.2018.01466.].
ABSTRACT
Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or de novo RNA synthesis by RNA-dependent RNA polymerase (RdRp). VPg is a multifunctional protein that plays crucial roles in viral protein translation and genome replication. However, the interaction between the RdRp and this multifunctional VPg in NoV replication has been unknown. In this study, VPg derived from murine NoV (MNV) was found to mediate the formation of higher-order multimers or tubular fibrils of MNV RdRp, which led to significantly enhanced polymerase activity in vitro. The replication of MNV mutants containing a VPg-binding defective RdRp, based on the crystal structure of an RdRp-VPg(1-73) complex, was completely blocked in a cell culture system. Our data suggest that the interaction between RdRp and VPg plays a crucial role in the multimerization-mediated RdRp activity in vivo and consequently in MNV replication, which can provide a new target of therapeutic intervention for NoV outbreaks.
ABSTRACT
OBJECTIVES/HYPOTHESIS: To investigate the clinical significance of three-dimensional-fluid-attenuated inversion recovery (3D-FLAIR) magnetic resonance imaging (MRI) findings in patients with Ramsay-Hunt syndrome (RHS). STUDY DESIGN: Case series. METHODS: We enrolled 28 consecutive patients of RHS with temporal bone MRI. Initial clinical findings and outcome were assessed by House-Brackmann (HB) scales, electroneuronography (ENoG), and pure tone audiometry (PTA). Two radiologists evaluated the presence of abnormalities on pre-/postcontrast 3D-FLAIR for the cranial nerve (CN)-VII, CN-VIII, inner ear (IE), and the posterior fossa by consensus. The relative signal intensity and enhancement degree (rED) of the structures were measured using ImageJ (http://rsbweb.nih.gov/ij/). Statistical test correlated the clinical symptoms and the outcome with the analysis results of 3D-FLAIR images. RESULTS: 3D-FLAIR demonstrated enhancement of CN-VII in all patients. Precontrast hyperintensity and enhancement were seen in eight and 16 patients with IE, and in four and six with CN-VIII, respectively. Precontrast hyperintensity of IE or CN-VIII was significantly associated with the presence of vertigo (P value < 0.05). Precontrast hyperintensity of IE or CN-VIII significantly correlated with clinical symptoms assessed by HB, ENoG, and PTA (P value < 0.05, respectively). rED of the vestibule moderately correlated with initial HB scale (r = 0.391, P = 0.039). There was no correlation between any of the 3D-FLAIR findings and the follow-up HB. CONCLUSIONS: RHS shows frequent abnormalities of IE or CN-VIII, as well as CN-VII on pre-/postcontrast 3D-FLAIR images. Precontrast hyperintensity of IE/CN-VIII on 3D-FLAIR is significantly correlated with the severity of facial palsy, the presence of vertigo, and the degree of hearing impairment but not with clinical outcome.
