Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis.
STING is a nodal point for cellular innate immune response to microbial infections, autoimmunity and cancer; it triggers the synthesis of the antiviral proteins, type I interferons. Many DNA viruses, including Herpes Simplex Virus 1 (HSV1), trigger STING signaling causing inhibition of virus replica...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-09-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1009950 |
| _version_ | 1798000163808083968 |
|---|---|
| author | Nikhil Sharma Chenyao Wang Patricia Kessler Ganes C Sen |
| author_facet | Nikhil Sharma Chenyao Wang Patricia Kessler Ganes C Sen |
| author_sort | Nikhil Sharma |
| collection | DOAJ |
| description | STING is a nodal point for cellular innate immune response to microbial infections, autoimmunity and cancer; it triggers the synthesis of the antiviral proteins, type I interferons. Many DNA viruses, including Herpes Simplex Virus 1 (HSV1), trigger STING signaling causing inhibition of virus replication. Here, we report that HSV1 evades this antiviral immune response by inducing a cellular microRNA, miR-24, which binds to the 3' untranslated region of STING mRNA and inhibits its translation. Expression of the gene encoding miR-24 is induced by the transcription factor AP1 and activated by MAP kinases in HSV1-infected cells. Introduction of exogenous miR-24 or prior activation of MAPKs, causes further enhancement of HSV1 replication in STING-expressing cells. Conversely, transfection of antimiR-24 inhibits virus replication in those cells. HSV1 infection of mice causes neuropathy and death; using two routes of infection, we demonstrated that intracranial injection of antimiR-24 alleviates both morbidity and mortality of the infected mice. Our studies reveal a new immune evasion strategy adopted by HSV1 through the regulation of STING and demonstrates that it can be exploited to enhance STING's antiviral action. |
| first_indexed | 2024-04-11T11:15:47Z |
| format | Article |
| id | doaj.art-0b799e19f3204017ab8357b547c7afe2 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-11T11:15:47Z |
| publishDate | 2021-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-0b799e19f3204017ab8357b547c7afe22022-12-22T04:27:14ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742021-09-01179e100995010.1371/journal.ppat.1009950Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis.Nikhil SharmaChenyao WangPatricia KesslerGanes C SenSTING is a nodal point for cellular innate immune response to microbial infections, autoimmunity and cancer; it triggers the synthesis of the antiviral proteins, type I interferons. Many DNA viruses, including Herpes Simplex Virus 1 (HSV1), trigger STING signaling causing inhibition of virus replication. Here, we report that HSV1 evades this antiviral immune response by inducing a cellular microRNA, miR-24, which binds to the 3' untranslated region of STING mRNA and inhibits its translation. Expression of the gene encoding miR-24 is induced by the transcription factor AP1 and activated by MAP kinases in HSV1-infected cells. Introduction of exogenous miR-24 or prior activation of MAPKs, causes further enhancement of HSV1 replication in STING-expressing cells. Conversely, transfection of antimiR-24 inhibits virus replication in those cells. HSV1 infection of mice causes neuropathy and death; using two routes of infection, we demonstrated that intracranial injection of antimiR-24 alleviates both morbidity and mortality of the infected mice. Our studies reveal a new immune evasion strategy adopted by HSV1 through the regulation of STING and demonstrates that it can be exploited to enhance STING's antiviral action.https://doi.org/10.1371/journal.ppat.1009950 |
| spellingShingle | Nikhil Sharma Chenyao Wang Patricia Kessler Ganes C Sen Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis. PLoS Pathogens |
| title | Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis. |
| title_full | Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis. |
| title_fullStr | Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis. |
| title_full_unstemmed | Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis. |
| title_short | Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis. |
| title_sort | herpes simplex virus 1 evades cellular antiviral response by inducing microrna 24 which attenuates sting synthesis |
| url | https://doi.org/10.1371/journal.ppat.1009950 |
| work_keys_str_mv | AT nikhilsharma herpessimplexvirus1evadescellularantiviralresponsebyinducingmicrorna24whichattenuatesstingsynthesis AT chenyaowang herpessimplexvirus1evadescellularantiviralresponsebyinducingmicrorna24whichattenuatesstingsynthesis AT patriciakessler herpessimplexvirus1evadescellularantiviralresponsebyinducingmicrorna24whichattenuatesstingsynthesis AT ganescsen herpessimplexvirus1evadescellularantiviralresponsebyinducingmicrorna24whichattenuatesstingsynthesis |