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J Virol. 2018 Jun 13. pii: JVI.00539-18. doi: 10.1128/JVI.00539-18. [Epub ahead of print]
Lnc-ISG20 inhibits influenza A virus replication by enhancing ISG20 expression.
Chai W1,2, Li J1, Shangguan Q1,2, Liu Q1,2, Li X1,2, Qi D1, Tong X1, Liu W1,3, Ye X4,3.
Author information
Abstract
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
Lnc-ISG20 inhibits influenza A virus replication by enhancing ISG20 expression.
Chai W1,2, Li J1, Shangguan Q1,2, Liu Q1,2, Li X1,2, Qi D1, Tong X1, Liu W1,3, Ye X4,3.
Author information
Abstract
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