Verification of SARS-CoV-2-encoded small RNAs and contribution to infection-associated lung inflammation.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang C
PROVIDER: S-EPMC9521766 | biostudies-literature | 2022 Jul
REPOSITORIES: biostudies-literature
Publications
Verification of SARS-CoV-2-encoded small RNAs and contribution to infection-associated lung inflammation.
Zhang Cheng C Liu Cheng C Jiang Lin L Cui Lunbiao L Li Chunyu C Song Guoxin G Xu Rui R Geng Xiangnan X Luan Changxing C Chen Feng F Chen Yan Y Zhu Baoli B Zhu Wei W
Chinese medical journal 20220805 15
Similar Datasets
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18-22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.
| S-EPMC5662013 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.
2017-02-14 | GSE90624 | GEO
Project description:Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, with viral E protein promoting the exacerbated inflammatory response. By deep sequencing RNAs from the lungs of infected mice, we have addressed the relevance of small, non-coding RNAs in SARS-CoV pathology. Host microRNAs (miRNAs) expressed during infection by a virulent virus encoding the E protein were significantly enriched for cytokine-mediated inflammatory pathways when compared with attenuated SARS-CoV-∆E, suggesting contribution of miRNAs to E protein-induced inflammation. The discovery of three 18-22 nt small viral RNAs (svRNAs) derived from the nsp3 and N genomic regions of SARS-CoV in mouse lung and cell cultures is also described. Depletion of these svRNAs significantly reduced viral titers and genomic RNA levels, indicating their positive contribution to virus growth. Remarkably, svRNA-N antagomirs significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression, indicating that svRNAs contribute to SARS-CoV pathogenesis and highlighting the potential of these antagomirs as antivirals.
2022-02-04 | GSE84081 | GEO
Project description: Not available
| EMPIAR-10533 | biostudies-other
Project description:Serine incorporator protein 5 (SERINC5) is a key innate immunity factor that operates in the cell to restrict the infectivity of certain viruses. Different viruses have developed strategies to antagonize SERINC5 function but, how SERINC5 is controlled during viral infection is poorly understood. Here, we report that SERINC5 levels are reduced in COVID-19 patients during the infection by SARS-CoV-2 and, since no viral protein capable of repressing the expression of SERINC5 has been identified, we hypothesized that SARS-CoV-2 non-coding small viral RNAs (svRNAs) could be responsible for this repression. Two newly identified svRNAs with predicted binding sites in the 3'-untranslated region (3'-UTR) of the SERINC5 gene were characterized and we found that the expression of both svRNAs during the infection was not dependent on the miRNA pathway proteins Dicer and Argonaute-2. By using svRNAs mimic oligonucleotides, we demonstrated that both viral svRNAs can bind the 3'UTR of SERINC5 mRNA, reducing SERINC5 expression in vitro. Moreover, we found that an anti-svRNA treatment to Vero E6 cells before SARS-CoV-2 infection recovered the levels of SERINC5 and reduced the levels of N and S viral proteins. Finally, we showed that SERINC5 positively controls the levels of Mitochondrial Antiviral Signalling (MAVS) protein in Vero E6. These results highlight the therapeutic potential of targeting svRNAs based on their action on key proteins of the innate immune response during SARS-CoV-2 viral infection.
| S-EPMC9978209 | biostudies-literature
Project description:The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 has resulted in enormous deaths around the world. Clues from genomic sequences of parent and their mutants can be obtained to understand the evolving pathogenesis of this virus. Apart from the viral proteins, virus-encoded microRNAs (miRNAs) have been shown to play a vital role in regulating viral pathogenesis. Thus we sought to investigate the miRNAs encoded by SARS-CoV-2, its mutants, and the host. Here, we present the results obtained using a dual approach i.e (i) identifying host-encoded miRNAs that might regulate viral pathogenesis and (ii) identifying viral-encoded miRNAs that might regulate host cell signaling pathways and aid in viral pathogenesis. Analysis utilizing the first approach resulted in the identification of ten host-encoded miRNAs that could target the SARS, SARS-CoV-2, and its mutants. Interestingly our analysis revealed that there is a significantly higher number of host miRNAs that could target the SARS-CoV-2 genome as compared to the SARS reference genome. Results from the second approach resulted in the identification of a set of virus-encoded miRNAs which might regulate host signaling pathways. Our analysis further identified a similar "GA" rich motif in the SARS-CoV-2 and its mutant genomes that was shown to play a vital role in lung pathogenesis during severe SARS infections. In summary, we have identified human and virus-encoded miRNAs that might regulate the pathogenesis of SARS coronaviruses and describe similar non-coding RNA sequences in SARS-CoV-2 that were shown to regulate SARS-induced lung pathology in mice.
| S-EPMC9742375 | biostudies-literature
Project description: Not available
| S-EPMC10901198 | biostudies-literature
Project description:Despite the success of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines, there remains a clear need for new classes of preventatives for respiratory viral infections due to vaccine hesitancy, lack of sterilizing immunity, and for at-risk patient populations, including the immunocompromised. While many neutralizing antibodies have been identified, and several approved, to treat COVID-19, systemic delivery, large doses, and high costs have the potential to limit their widespread use, especially in low- and middle-income countries. To use these antibodies more efficiently, an inhalable formulation is developed that allows for the expression of mRNA-encoded, membrane-anchored neutralizing antibodies in the lung to mitigate SARS-CoV-2 infections. First, the ability of mRNA-encoded, membrane-anchored, anti-SARS-CoV-2 antibodies to prevent infections in vitro is demonstrated. Next, it is demonstrated that nebulizer-based delivery of these mRNA-expressed neutralizing antibodies potently abrogates disease in the hamster model. Overall, these results support the use of nebulizer-based mRNA expression of neutralizing antibodies as a new paradigm for mitigating respiratory virus infections.
| S-EPMC9731714 | biostudies-literature
Project description:To explore the relationship between SARS-CoV-2 infection in different time before operation and postoperative main complications (mortality, main pulmonary and cardiovascular complications) 30 days after operation; To determine the best timing of surgery after SARS-CoV-2 infection.
| 12454 | ecrin-mdr-crc
Project description:Cleavage of double-stranded RNA is described as an evolutionary conserved host defense mechanism against viral infection. Small RNAs are the product and triggers of post transcriptional gene silencing events. Up until now, the relevance of this mechanism for SARS-CoV-2-directed immune responses remains elusive. Herein, we used high throughput sequencing to profile the plasma of active and convalescent COVID-19 patients for the presence of small circulating RNAs. The existence of SARS-CoV-2 derived small RNAs in plasma samples of mild and severe COVID-19 cases is described. Clusters of high siRNA abundance were discovered, homologous to the nsp2 3'-end and nsp4 virus sequence. Four virus-derived small RNA sequences have the size of human miRNAs, and a target search revealed candidate genes associated with ageusia and long COVID symptoms. These virus-derived small RNAs were detectable also after recovery from the disease. The additional analysis of circulating human miRNAs revealed differentially abundant miRNAs, discriminating mild from severe cases. A total of 29 miRNAs were reduced or absent in severe cases. Several of these are associated with JAK-STAT response and cytokine storm.
| S-EPMC8402885 | biostudies-literature