Tsujimura, K. | Search bioRxiv

bioRxiv2025

Equine herpesvirus myeloencephalopathy-related mutations in EHV-1 DNA polymerase allow EHV-1 to grow at elevated temperatures

Equine herpesvirus myeloencephalopathy (EHM) caused by equine herpesvirus type 1 (EHV-1) is a major threat to the equine industry because of its devastatating impact on animal welfare and performance. A specific single nucleotide polymorphism (SNP) (G2254/D752) in the EHV-1 ORF30 gene encoding DNA polymerase was previously shown to be a marker of the strain of EHV-1 that causes EHM. However, the effect of this SNP has never been resolved. Clinical findings indicated that fever and higher viremia levels are associated with the onset of EHM. No studies have examined EHV-1 growth at elevated temperatures so far. We found that EHV-1 with the D752 SNP replicated at elevated temperatures, and EHV-1 without it did not. We also found that EHV-1s isolated from horses with EHM could grow at elevated temperatures and most non-EHM isolates were suppressed by elevated temperatures. EHV-1s that can replicate at elevated temperatures have this SNP or one other SNP in ORF30. This appears to be the first report to show an association between EHM and the ability of EHV-1 to grow at elevated temperatures. (177 words) ImportanceEquine herpesvirus myeloencephalopathy (EHM) caused by equine herpesvirus type 1 (EHV-1) is a major threat to the equine industry because of its impact on animal welfare and performance. A specific single nucleotide polymorphism (SNP) (G2254/D752) in EHV-1 ORF30 gene encoding DNA polymerase (UL30) was previously shown to be a marker of EHM. However, the effect of this SNP has never been resolved. Here we show that this and one other SNP in UL30 are associated with replication capacity at elevated temperatures. (81 words)

microbiology↗

bioRxiv2025

MeCP2 controls dendritic morphogenesis via miR-199a-mediated Qki downregulation

Rett syndrome (RTT) (OMIM: 312750) is a severe neurodevelopmental disorder caused by mutations in the MECP2 gene. Although decreased dendritic morphogenesis has been observed in the brain of RTT patients and mouse models, the molecular mechanisms underlying these dendritic anomalies remain unclear. We have previously shown that MeCP2 facilitates specific microRNA (miRNA) processing by associating with the miRNA microprocessor Drosha complex. In this study, we show that MeCP2 positively regulates dendritic formation via miR-199a, a specific target of the MeCP2-Drosha complex. Overexpression of MeCP2 and miR-199a promotes dendritic development such as increases in dendrite length, branching number, and complexity. In contrast, blocking miR-199a inhibited dendrite formation and abolished enhanced dendritic development induced by MeCP2 expression. We also demonstrate that the decreased dendrite outgrowth observed in MeCP2-deficient neurons could be rescued by miR-199a expression. In addition, we found that miR-199a targets the 3 untranslated region of quaking (Qki), a negative regulator of dendritic development, and downregulates its protein expression level. Furthermore, we report an increase in the Qki protein expression level in miR-199a-2-deficient brains and show that Qki knockdown restores the dendritic morphology of miR-199a-2-Knockout (KO) neurons. Taken together, these results suggest that the MeCP2/miR-199a/Qki axis is critical for proper dendritic development and its dysregulation contributes to the dendritic pathology in RTT.

neuroscience↗