RESUMO
The COVID-19 pandemic is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The betacoronvirus has a positive sense RNA genome which encodes for several RNA binding proteins. Here, we use enhanced crosslinking and immunoprecipitation to investigate SARS-CoV-2 protein interactions with viral and host RNAs in authentic virus-infected cells. SARS-CoV-2 proteins, NSP8, NSP12, and nucleocapsid display distinct preferences to specific regions in the RNA viral genome, providing evidence for their shared and separate roles in replication, transcription, and viral packaging. SARS-CoV-2 proteins expressed in human lung epithelial cells bind to 4773 unique host coding RNAs. Nine SARS-CoV-2 proteins upregulate target gene expression, including NSP12 and ORF9c, whose RNA substrates are associated with pathways in protein N-linked glycosylation ER processing and mitochondrial processes. Furthermore, siRNA knockdown of host genes targeted by viral proteins in human lung organoid cells identify potential antiviral host targets across different SARS-CoV-2 variants. Conversely, NSP9 inhibits host gene expression by blocking mRNA export and dampens cytokine productions, including interleukin-1/{beta}. Our viral protein-RNA interactome provides a catalog of potential therapeutic targets and offers insight into the etiology of COVID-19 as a safeguard against future pandemics.
RESUMO
Objective@#To investigate the safety and efficacy of transcatheter perforation of pulmonary valve by micro-guidewire and balloon dilation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS).@*Methods@#The retrospective study included 21 neonates (14 males and 7 females) with PA-IVS who underwent transcatheter micro-guidewire pulmonary valve perforation and balloon dilation in Xinhua Hospital from January 2012 to December 2018. All patients underwent the pulmonary valve perforation by micro-guidewire through the Simmons catheter. During the follow-up period at 1, 3, 6, 12 months postoperatively and annually thereafter, the operative efficacy and the development of the right ventricle (RV) were evaluated by echocardiography. Statistical analyses were performed using t test.@*Results@#A total of 21 neonates with PA-IVS were enrolled, and 13 cases were diagnosed prenatally. The median age of surgery was 6 days, the weight was (3.2±0.5) kg. The balloon/valve ratio was 1.19±0.12, and the RV pressure measured by catheter was (121±33) mmHg (1 mmHg=0.133 kPa) . The immediate postoperative RV pressure was (47±13) mmHg. The median follow-up time was 30 months. All the cases enrolled achieved biventricular circulation without death and serious complications. According to the last follow-up data including 16 cases who were followed up for 1 year or longer, the pulmonary artery transvalvular pressure was (29±15) mmHg. The postoperation ratio of right to left ventricular transverse diameter was significantly higher than that before operation (0.86+0.10 vs. 0.73+0.13, t=-2.96, P=0.006). Compared with preoperative data, the postoperation pulmonary valvular diameter Z-score was significantly higher (-1.41±0.89 vs. -2.83±1.06, t=-3.65, P=0.001) and the tricuspid valvular diameter Z-score was significantly higher (-0.52±0.29 vs. -1.34±0.81, t=-3.55, P=0.001).@*Conclusion@#Transcatheter perforation of pulmonary valve by micro-guidewire and balloon dilation is a safe and effective initial therapy for neonatal PA-IVS.
