tetano
Editor, Senior Moderator
J Biomed Sci. 2019 Aug 15;26(1):58. doi: 10.1186/s12929-019-0553-6.
[h=1]Exosome-delivered and Y RNA-derived small RNA suppresses influenza virus replication.[/h] Liu YM[SUP]1,[/SUP][SUP]2[/SUP], Tseng CH[SUP]3,[/SUP][SUP]4[/SUP], Chen YC[SUP]2[/SUP], Yu WY[SUP]5[/SUP], Ho MY[SUP]5[/SUP], Ho CY[SUP]5[/SUP], Lai MMC[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Su WC[SUP]8,[/SUP][SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h] 1 Graduate Institute of Clinical Medical Science, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. 2 Division of Infectious Diseases, Changhua Christian Medical Foundation Changhua Christian Hospital, No. 135, Nanxiao St., Changhua City, Changhua County, 500, Taiwan. 3 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, No. 1, Daxue Rd., East Dist, Tainan City, 701, Taiwan. 4 Center of Infectious Disease and Signaling Research, National Cheng Kung University, No. 1, Daxue Rd., East Dist, Tainan City, 701, Taiwan. 5 Research Center for Emerging Viruses, China Medical University Hospital, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. 6 Graduate Institute of Biomedical Sciences, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. 7 Institute of Molecular Biology, Academia Sinica, No. 128, Sec. 2, Academia Rd., Nangang Dist, Taipei City, 115, Taiwan. 8 Graduate Institute of Clinical Medical Science, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. t23514@mail.cmuh.org.tw. 9 Research Center for Emerging Viruses, China Medical University Hospital, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. t23514@mail.cmuh.org.tw. 10 Graduate Institute of Biomedical Sciences, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. t23514@mail.cmuh.org.tw.
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Multiple interplays between viral and host factors are involved in influenza virus replication and pathogenesis. Several small RNAs have recently emerged as important regulators of host response to viral infections. The aim of this study was to characterize the functional role of hsa-miR-1975, a Y5 RNA-derived small RNA, in defending influenza virus and delineate the mechanisms.
[h=4]METHODS:[/h] We performed high throughput sequencing of small RNAs in influenza virus-infected cells to identify up- or down- regulated small RNA species. The expression of the most abundant RNA species (hsa-miR-1975) was validated by stem-loop reverse transcription-polymerase chain reaction (RT-PCR). Antiviral effects of hsa-miR-1975 were confirmed by Western Blot, RT-PCR and plaque assay. In vitro perturbation of hsa-miR-1975 combined with exosomes isolation was used to elucidate the role and mechanism of hsa-miR-1975 in the context of antiviral immunity.
[h=4]RESULTS:[/h] Small RNA sequencing revealed that hsa-miR-1975 was the most up-regulated small RNA in influenza virus-infected cells. The amount of intracellular hsa-miR-1975 increased in the late stage of the influenza virus replication cycle. The increased hsa-miR-1975 was at least partially derived from degradation of Y5RNA as a result of cellular apoptosis. Unexpectedly, hsa-miR-1975 mimics inhibited influenza virus replication while hsa-miR-1975 sponges enhanced the virus replication. Moreover, hsa-miR-1975 was secreted in exosomes and taken up by the neighboring cells to induce interferon expression.
[h=4]CONCLUSIONS:[/h] Our findings unravel a critical role of Y-class small RNA in host's defense against influenza virus infection and reveal its antiviral mechanism through exosome delivery. This may provide a new candidate for targeting influenza virus.
[h=4]KEYWORDS:[/h] Exosome; Hsa-miR-1975; Influenza virus; Interferon; Y RNA
PMID: 31416454 PMCID: PMC6694579 DOI: 10.1186/s12929-019-0553-6
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[h=1]Exosome-delivered and Y RNA-derived small RNA suppresses influenza virus replication.[/h] Liu YM[SUP]1,[/SUP][SUP]2[/SUP], Tseng CH[SUP]3,[/SUP][SUP]4[/SUP], Chen YC[SUP]2[/SUP], Yu WY[SUP]5[/SUP], Ho MY[SUP]5[/SUP], Ho CY[SUP]5[/SUP], Lai MMC[SUP]4,[/SUP][SUP]5,[/SUP][SUP]6,[/SUP][SUP]7[/SUP], Su WC[SUP]8,[/SUP][SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h] 1 Graduate Institute of Clinical Medical Science, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. 2 Division of Infectious Diseases, Changhua Christian Medical Foundation Changhua Christian Hospital, No. 135, Nanxiao St., Changhua City, Changhua County, 500, Taiwan. 3 Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, No. 1, Daxue Rd., East Dist, Tainan City, 701, Taiwan. 4 Center of Infectious Disease and Signaling Research, National Cheng Kung University, No. 1, Daxue Rd., East Dist, Tainan City, 701, Taiwan. 5 Research Center for Emerging Viruses, China Medical University Hospital, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. 6 Graduate Institute of Biomedical Sciences, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. 7 Institute of Molecular Biology, Academia Sinica, No. 128, Sec. 2, Academia Rd., Nangang Dist, Taipei City, 115, Taiwan. 8 Graduate Institute of Clinical Medical Science, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. t23514@mail.cmuh.org.tw. 9 Research Center for Emerging Viruses, China Medical University Hospital, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. t23514@mail.cmuh.org.tw. 10 Graduate Institute of Biomedical Sciences, China Medical University, No.91, Xueshi Rd., North Dist, Taichung City, 404, Taiwan. t23514@mail.cmuh.org.tw.
[h=3]Abstract[/h] [h=4]BACKGROUND:[/h] Multiple interplays between viral and host factors are involved in influenza virus replication and pathogenesis. Several small RNAs have recently emerged as important regulators of host response to viral infections. The aim of this study was to characterize the functional role of hsa-miR-1975, a Y5 RNA-derived small RNA, in defending influenza virus and delineate the mechanisms.
[h=4]METHODS:[/h] We performed high throughput sequencing of small RNAs in influenza virus-infected cells to identify up- or down- regulated small RNA species. The expression of the most abundant RNA species (hsa-miR-1975) was validated by stem-loop reverse transcription-polymerase chain reaction (RT-PCR). Antiviral effects of hsa-miR-1975 were confirmed by Western Blot, RT-PCR and plaque assay. In vitro perturbation of hsa-miR-1975 combined with exosomes isolation was used to elucidate the role and mechanism of hsa-miR-1975 in the context of antiviral immunity.
[h=4]RESULTS:[/h] Small RNA sequencing revealed that hsa-miR-1975 was the most up-regulated small RNA in influenza virus-infected cells. The amount of intracellular hsa-miR-1975 increased in the late stage of the influenza virus replication cycle. The increased hsa-miR-1975 was at least partially derived from degradation of Y5RNA as a result of cellular apoptosis. Unexpectedly, hsa-miR-1975 mimics inhibited influenza virus replication while hsa-miR-1975 sponges enhanced the virus replication. Moreover, hsa-miR-1975 was secreted in exosomes and taken up by the neighboring cells to induce interferon expression.
[h=4]CONCLUSIONS:[/h] Our findings unravel a critical role of Y-class small RNA in host's defense against influenza virus infection and reveal its antiviral mechanism through exosome delivery. This may provide a new candidate for targeting influenza virus.
[h=4]KEYWORDS:[/h] Exosome; Hsa-miR-1975; Influenza virus; Interferon; Y RNA
PMID: 31416454 PMCID: PMC6694579 DOI: 10.1186/s12929-019-0553-6
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