TY - JOUR
T1 - The Landscape of Expressed Chimeric Transcripts in the Blood of Severe COVID-19 Infected Patients
AU - Mukherjee, Sunanda Biswas
AU - Detroja, Rajesh
AU - Mukherjee, Sumit
AU - Frenkel-Morgenstern, Milana
N1 - Funding Information: The authors thank members of the Cancer Genomics and Biocomputing of Complex Diseases Lab for multiple discussions at different stages of this project. S.M. is thankful to the National Institutes of Health (NIH), USA, for providing a postdoctoral visiting fellowship award. Publisher Copyright: © 2023 by the authors.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - The ongoing COVID-19 pandemic caused by SARS-CoV-2 infections has quickly developed into a global public health threat. COVID-19 patients show distinct clinical features, and in some cases, during the severe stage of the condition, the disease severity leads to an acute respiratory disorder. In spite of several pieces of research in this area, the molecular mechanisms behind the development of disease severity are still not clearly understood. Recent studies demonstrated that SARS-CoV-2 alters the host cell splicing and transcriptional response to overcome the host immune response that provides the virus with favorable conditions to replicate efficiently within the host cells. In several disease conditions, aberrant splicing could lead to the development of novel chimeric transcripts that could promote the functional alternations of the cell. As severe SARS-CoV-2 infection was reported to cause abnormal splicing in the infected cells, we could expect the generation and expression of novel chimeric transcripts. However, no study so far has attempted to check whether novel chimeric transcripts are expressed in severe SARS-CoV-2 infections. In this study, we analyzed several publicly available blood transcriptome datasets of severe COVID-19, mild COVID-19, other severe respiratory viral infected patients, and healthy individuals. We identified 424 severe COVID-19 -specific chimeric transcripts, 42 of which were recurrent. Further, we detected 189 chimeric transcripts common to severe COVID-19 and multiple severe respiratory viral infections. Pathway and gene enrichment analysis of the parental genes of these two subsets of chimeric transcripts reveals that these are potentially involved in immune-related processes, interferon signaling, and inflammatory responses, which signify their potential association with immune dysfunction leading to the development of disease severity. Our study provides the first detailed expression landscape of chimeric transcripts in severe COVID-19 and other severe respiratory viral infections.
AB - The ongoing COVID-19 pandemic caused by SARS-CoV-2 infections has quickly developed into a global public health threat. COVID-19 patients show distinct clinical features, and in some cases, during the severe stage of the condition, the disease severity leads to an acute respiratory disorder. In spite of several pieces of research in this area, the molecular mechanisms behind the development of disease severity are still not clearly understood. Recent studies demonstrated that SARS-CoV-2 alters the host cell splicing and transcriptional response to overcome the host immune response that provides the virus with favorable conditions to replicate efficiently within the host cells. In several disease conditions, aberrant splicing could lead to the development of novel chimeric transcripts that could promote the functional alternations of the cell. As severe SARS-CoV-2 infection was reported to cause abnormal splicing in the infected cells, we could expect the generation and expression of novel chimeric transcripts. However, no study so far has attempted to check whether novel chimeric transcripts are expressed in severe SARS-CoV-2 infections. In this study, we analyzed several publicly available blood transcriptome datasets of severe COVID-19, mild COVID-19, other severe respiratory viral infected patients, and healthy individuals. We identified 424 severe COVID-19 -specific chimeric transcripts, 42 of which were recurrent. Further, we detected 189 chimeric transcripts common to severe COVID-19 and multiple severe respiratory viral infections. Pathway and gene enrichment analysis of the parental genes of these two subsets of chimeric transcripts reveals that these are potentially involved in immune-related processes, interferon signaling, and inflammatory responses, which signify their potential association with immune dysfunction leading to the development of disease severity. Our study provides the first detailed expression landscape of chimeric transcripts in severe COVID-19 and other severe respiratory viral infections.
KW - aberrant splicing
KW - chimeric transcripts
KW - cis-SAGe
KW - respiratory viral infections
KW - severe COVID-19
UR - http://www.scopus.com/inward/record.url?scp=85148966677&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/v15020433
DO - https://doi.org/10.3390/v15020433
M3 - Article
C2 - 36851647
SN - 1999-4915
VL - 15
JO - Viruses
JF - Viruses
IS - 2
M1 - 433
ER -
