tetano
Editor, Senior Moderator
J Virol. 2018 Jun 13. pii: JVI.00539-18. doi: 10.1128/JVI.00539-18. [Epub ahead of print]
[h=1]Lnc-ISG20 inhibits influenza A virus replication by enhancing ISG20 expression.[/h] Chai W[SUP]1,[/SUP][SUP]2[/SUP], Li J[SUP]1[/SUP], Shangguan Q[SUP]1,[/SUP][SUP]2[/SUP], Liu Q[SUP]1,[/SUP][SUP]2[/SUP], Li X[SUP]1,[/SUP][SUP]2[/SUP], Qi D[SUP]1[/SUP], Tong X[SUP]1[/SUP], Liu W[SUP]1,[/SUP][SUP]3[/SUP], Ye X[SUP]4,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] LncRNAs are involved in many aspects of cellular processes, including antiviral immune response. To identify influenza A virus (IAV)-related lncRNAs, we performed RNA-deep sequencing to compare the profiles of lncRNAs in A549 and 293T cells with or without IAV infection. We identified an IAV-upregulated lncRNA named lnc-ISG20 because it shares most of its sequence with ISG20. We found that lnc-ISG20 is an interferon-stimulated gene similar to ISG20. Overexpression of lnc-ISG20 inhibited IAV replication, while lnc-ISG20 knockdown favored viral replication, suggesting that ln-ISG20 is inhibitory to IAV replication. Further study indicated that overexpression of lnc-ISG20 enhances ISG20 protein levels, while knockdown of lnc-ISG20 reduced ISG20 protein levels in A549 cells induced with polyI:C and Sendai virus. We demonstrated that lnc-ISG20 inhibits IAV replication in an ISG20-dependent manner. As lnc-ISG20 did not affect the mRNA level of ISG20, we postulated that lnc-ISG20 may function as competing endogenous RNA to ISG20 to enhance its translation. Indeed, we identified that miR-326 is a mutual miRNA for both ISG20 and lnc-ISG20 that targets the 3'UTR of ISG20 mRNA to inhibit its translation. We confirmed that lnc-ISG20 can bind miR-326, which in turn decreased the amount of miR-326 bound to ISG20 mRNA. In conclusion, we identified that the IAV-upregulated lnc-ISG20 is a novel interferon-stimulating gene that elicits its inhibitory effect on IAV replication by enhancing ISG20 expression. We demonstrated that lnc-ISG20 functions as a ceRNA to bind miR-326 to reduce its inhibition on ISG20 translation. Our results revealed the mechanism by which lnc-ISG20 inhibits IAV replication.ImportanceThe replication of Influenza A virus is regulated by host factors. However, the mechanisms by which lncRNAs regulate IAV infection are not well understood. We identified that lnc-ISG20 is up-regulated during IAV infection and is also an interferon-stimulated gene. We demonstrated that lnc-ISG20 can enhance ISG20 expression, which in turn inhibits IAV replication. Our studies indicate that lnc-ISG20 functions as a competing endogenous RNA that binds miR-326 and reduces its inhibitory effect on ISG20. Taken together, our findings reveal the mechanistic details of lnc-ISG20 negatively regulating IAV replication. These findings indicate that lnc-ISG20 plays an important role during the host antiviral immune response.
PMID: 29899085 DOI: 10.1128/JVI.00539-18
[h=1]Lnc-ISG20 inhibits influenza A virus replication by enhancing ISG20 expression.[/h] Chai W[SUP]1,[/SUP][SUP]2[/SUP], Li J[SUP]1[/SUP], Shangguan Q[SUP]1,[/SUP][SUP]2[/SUP], Liu Q[SUP]1,[/SUP][SUP]2[/SUP], Li X[SUP]1,[/SUP][SUP]2[/SUP], Qi D[SUP]1[/SUP], Tong X[SUP]1[/SUP], Liu W[SUP]1,[/SUP][SUP]3[/SUP], Ye X[SUP]4,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] LncRNAs are involved in many aspects of cellular processes, including antiviral immune response. To identify influenza A virus (IAV)-related lncRNAs, we performed RNA-deep sequencing to compare the profiles of lncRNAs in A549 and 293T cells with or without IAV infection. We identified an IAV-upregulated lncRNA named lnc-ISG20 because it shares most of its sequence with ISG20. We found that lnc-ISG20 is an interferon-stimulated gene similar to ISG20. Overexpression of lnc-ISG20 inhibited IAV replication, while lnc-ISG20 knockdown favored viral replication, suggesting that ln-ISG20 is inhibitory to IAV replication. Further study indicated that overexpression of lnc-ISG20 enhances ISG20 protein levels, while knockdown of lnc-ISG20 reduced ISG20 protein levels in A549 cells induced with polyI:C and Sendai virus. We demonstrated that lnc-ISG20 inhibits IAV replication in an ISG20-dependent manner. As lnc-ISG20 did not affect the mRNA level of ISG20, we postulated that lnc-ISG20 may function as competing endogenous RNA to ISG20 to enhance its translation. Indeed, we identified that miR-326 is a mutual miRNA for both ISG20 and lnc-ISG20 that targets the 3'UTR of ISG20 mRNA to inhibit its translation. We confirmed that lnc-ISG20 can bind miR-326, which in turn decreased the amount of miR-326 bound to ISG20 mRNA. In conclusion, we identified that the IAV-upregulated lnc-ISG20 is a novel interferon-stimulating gene that elicits its inhibitory effect on IAV replication by enhancing ISG20 expression. We demonstrated that lnc-ISG20 functions as a ceRNA to bind miR-326 to reduce its inhibition on ISG20 translation. Our results revealed the mechanism by which lnc-ISG20 inhibits IAV replication.ImportanceThe replication of Influenza A virus is regulated by host factors. However, the mechanisms by which lncRNAs regulate IAV infection are not well understood. We identified that lnc-ISG20 is up-regulated during IAV infection and is also an interferon-stimulated gene. We demonstrated that lnc-ISG20 can enhance ISG20 expression, which in turn inhibits IAV replication. Our studies indicate that lnc-ISG20 functions as a competing endogenous RNA that binds miR-326 and reduces its inhibitory effect on ISG20. Taken together, our findings reveal the mechanistic details of lnc-ISG20 negatively regulating IAV replication. These findings indicate that lnc-ISG20 plays an important role during the host antiviral immune response.
PMID: 29899085 DOI: 10.1128/JVI.00539-18