Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection
Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/6/1338 |
| _version_ | 1797481324930400256 |
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| author | William Rodriguez Mandy Muller |
| author_facet | William Rodriguez Mandy Muller |
| author_sort | William Rodriguez |
| collection | DOAJ |
| description | Since its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell. |
| first_indexed | 2024-03-09T22:12:55Z |
| format | Article |
| id | doaj.art-04cc7fb13cfb43018e6fef420c781389 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T22:12:55Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-04cc7fb13cfb43018e6fef420c7813892023-11-23T19:27:43ZengMDPI AGViruses1999-49152022-06-01146133810.3390/v14061338Shiftless, a Critical Piece of the Innate Immune Response to Viral InfectionWilliam Rodriguez0Mandy Muller1Department of Microbiology, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Microbiology, University of Massachusetts Amherst, Amherst, MA 01003, USASince its initial characterization in 2016, the interferon stimulated gene Shiftless (SHFL) has proven to be a critical piece of the innate immune response to viral infection. SHFL expression stringently restricts the replication of multiple DNA, RNA, and retroviruses with an extraordinary diversity of mechanisms that differ from one virus to the next. These inhibitory strategies include the negative regulation of viral RNA stability, translation, and even the manipulation of RNA granule formation during viral infection. Even more surprisingly, SHFL is the first human protein found to directly inhibit the activity of the -1 programmed ribosomal frameshift, a translation recoding strategy utilized across nearly all domains of life and several human viruses. Recent literature has shown that SHFL expression also significantly impacts viral pathogenesis in mouse models, highlighting its in vivo efficacy. To help reconcile the many mechanisms by which SHFL restricts viral replication, we provide here a comprehensive review of this complex ISG, its influence over viral RNA fate, and the implications of its functions on the virus-host arms race for control of the cell.https://www.mdpi.com/1999-4915/14/6/1338C19ORF66FLJ11286shiftlessSVA-1RyDENIRAV |
| spellingShingle | William Rodriguez Mandy Muller Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection Viruses C19ORF66 FLJ11286 shiftless SVA-1 RyDEN IRAV |
| title | Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection |
| title_full | Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection |
| title_fullStr | Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection |
| title_full_unstemmed | Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection |
| title_short | Shiftless, a Critical Piece of the Innate Immune Response to Viral Infection |
| title_sort | shiftless a critical piece of the innate immune response to viral infection |
| topic | C19ORF66 FLJ11286 shiftless SVA-1 RyDEN IRAV |
| url | https://www.mdpi.com/1999-4915/14/6/1338 |
| work_keys_str_mv | AT williamrodriguez shiftlessacriticalpieceoftheinnateimmuneresponsetoviralinfection AT mandymuller shiftlessacriticalpieceoftheinnateimmuneresponsetoviralinfection |