Deep sequencing of the mouse lung transcriptome reveals distinct long non-coding RNAs expression associated with the high virulence of H5N1 avian influenza virus in mice

Abstract

Long non-coding RNAs (lncRNAs) play multiple key regulatory roles in various biological processes. However, their function in influenza A virus (IAV) pathogenicity remains largely unexplored. Here, using next generation sequencing, we systemically compared the whole-transcriptome response of the mouse lung infected with either the highly pathogenic (A/Chicken/Jiangsu/k0402/2010, CK10) or the nonpathogenic (A/Goose/Jiangsu/k0403/2010, GS10) H5N1 virus. A total of 126 significantly differentially expressed (SDE) lncRNAs from three replicates were identified to be associated with the high virulence of CK10, whereas 94 SDE lncRNAs were related with GS10. Functional category analysis suggested that the SDE lncRNAs-coexpressed mRNAs regulated by CK10 were highly related with aberrant and uncontrolled inflammatory responses. Further canonical pathway analysis also confirmed that these targets were highly enriched for inflammatory-related pathways. Moreover, 9 lncRNAs and 17 lncRNAs-coexpressed mRNAs associated with a large number of targeted genes were successfully verified by qRT-PCR. One targeted lncRNA (NONMMUT011061) that was markedly activated and correlated with a great number of mRNAs was selected for further in-depth analysis, including predication of transcription factors, potential interacting proteins, genomic location, coding ability and construction of the secondary structure. More importantly, NONMMUT011061 was also distinctively stimulated during the highly pathogenic H5N8 virus infection in mice, suggesting a potential universal role of NONMMUT011061 in the pathogenesis of different H5 IAV. Altogether, these results provide a subset of lncRNAs that might play important roles in the pathogenesis of influenza virus and add the lncRNAs to the vast repertoire of host factors utilized by IAV for infection and persistence.

Roles of lncRNAs in influenza virus infection

“…These distinct expression profiles of lncRNAs in cells infected with different strains of IAV suggest an association between the expression of lncRNAs and host susceptibility to different IAV infections [22]. In support of the above observations, deep sequencing of lung RNA in mice that were challenged with a highly pathogenic (A/Chicken/Jiangsu/k0402/ 2010) or a much less virulent (A/Goose/Jiangsu/ k0403/2010) avian influenza virus H5N1 also showed distinct expression of numerous lncRNAs in response to these two viruses, and the lncRNA profiles are correlated with viral pathogenicity in mice [23]. These comprehensive studies have used different approaches to investigate the response of lncRNA expression to IAV infection under various conditions, including infection with different IAV strains, avian influenza virus with different pathogenicity, in different cell lines, or in mice.…”

NOD-like receptors mediate inflammatory lung injury during plateau hypoxia exposure

“…With the increasing progress of transcriptomic technology, lung transcriptome sequencing has been studied extensively. The transcriptome sequence of the lung in mice infected with influenza A virus [ 29 ] and that of the PRRSV infection in porcine lungs [ 30 ] have been analyzed. Meanwhile, other research focuses on transcriptome analysis of sick or cancerous lungs [ 31 – 33 ].…”

Response to a DNA vaccine against the H5N1 virus depending on the chicken line and number of doses

“…That explains the relatively high representation of RNA-encoding DEGs in our results. Moreover, mammalian long non-coding RNAs (lncRNAs) were reported to play critical roles in the immune response to influenza A virus infection [33], and some lncRNAs were identified as being related to the immune response to influenza A virus in ducks [34]; however, the roles of many non-coding RNAs remain to be discovered. Interestingly, the proportion of RNAencoding DEGs of all DEGs is far less in broilers (the Ross [2x] group) than in all remaining groups (Fig.…”