Attenuation of influenza A virus mRNA levels by promoter mutations.
We have engineered influenza A/WSN/33 viruses which have viral RNA (vRNA) segments with altered base pairs in the conserved double-stranded region of their vRNA promoters. The mutations were introduced into the segment coding for the neuraminidase (NA) by using a reverse genetics system. Two of the...
| Hoofdauteurs: | , , , |
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| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
1998
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| _version_ | 1826288409679757312 |
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| author | Fodor, E Palese, P Brownlee, G García-Sastre, A |
| author_facet | Fodor, E Palese, P Brownlee, G García-Sastre, A |
| author_sort | Fodor, E |
| collection | OXFORD |
| description | We have engineered influenza A/WSN/33 viruses which have viral RNA (vRNA) segments with altered base pairs in the conserved double-stranded region of their vRNA promoters. The mutations were introduced into the segment coding for the neuraminidase (NA) by using a reverse genetics system. Two of the rescued viruses which share a C-G-->A-U double mutation at positions 11 and 12' at the 3' and 5' ends of the NA-specific vRNA, respectively, showed approximately a 10-fold reduction of NA levels. The mutations did not dramatically affect the NA-specific vRNA levels found in virions or the NA-specific vRNA and cRNA levels in infected cells. In contrast, there was a significant decrease in the steady-state levels of NA-specific mRNAs in infected cells. Transcription studies in vitro with ribonucleoprotein complexes isolated from the two transfectant viruses indicated that transcription initiation of the NA-specific segment was not affected. However, the majority of NA-specific transcripts lacked poly(A) tails, suggesting that mutations in the double-stranded region of the influenza virus vRNA promoter can attenuate polyadenylation of mRNA molecules. This is the first time that a promoter mutation in an engineered influenza virus has shown a differential effect on influenza virus RNA transcription and replication. |
| first_indexed | 2024-03-07T02:13:16Z |
| format | Journal article |
| id | oxford-uuid:a15d49fe-9b04-4332-a23a-0acdd3504b6d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:13:16Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:a15d49fe-9b04-4332-a23a-0acdd3504b6d2022-03-27T02:12:38ZAttenuation of influenza A virus mRNA levels by promoter mutations.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a15d49fe-9b04-4332-a23a-0acdd3504b6dEnglishSymplectic Elements at Oxford1998Fodor, EPalese, PBrownlee, GGarcía-Sastre, AWe have engineered influenza A/WSN/33 viruses which have viral RNA (vRNA) segments with altered base pairs in the conserved double-stranded region of their vRNA promoters. The mutations were introduced into the segment coding for the neuraminidase (NA) by using a reverse genetics system. Two of the rescued viruses which share a C-G-->A-U double mutation at positions 11 and 12' at the 3' and 5' ends of the NA-specific vRNA, respectively, showed approximately a 10-fold reduction of NA levels. The mutations did not dramatically affect the NA-specific vRNA levels found in virions or the NA-specific vRNA and cRNA levels in infected cells. In contrast, there was a significant decrease in the steady-state levels of NA-specific mRNAs in infected cells. Transcription studies in vitro with ribonucleoprotein complexes isolated from the two transfectant viruses indicated that transcription initiation of the NA-specific segment was not affected. However, the majority of NA-specific transcripts lacked poly(A) tails, suggesting that mutations in the double-stranded region of the influenza virus vRNA promoter can attenuate polyadenylation of mRNA molecules. This is the first time that a promoter mutation in an engineered influenza virus has shown a differential effect on influenza virus RNA transcription and replication. |
| spellingShingle | Fodor, E Palese, P Brownlee, G García-Sastre, A Attenuation of influenza A virus mRNA levels by promoter mutations. |
| title | Attenuation of influenza A virus mRNA levels by promoter mutations. |
| title_full | Attenuation of influenza A virus mRNA levels by promoter mutations. |
| title_fullStr | Attenuation of influenza A virus mRNA levels by promoter mutations. |
| title_full_unstemmed | Attenuation of influenza A virus mRNA levels by promoter mutations. |
| title_short | Attenuation of influenza A virus mRNA levels by promoter mutations. |
| title_sort | attenuation of influenza a virus mrna levels by promoter mutations |
| work_keys_str_mv | AT fodore attenuationofinfluenzaavirusmrnalevelsbypromotermutations AT palesep attenuationofinfluenzaavirusmrnalevelsbypromotermutations AT brownleeg attenuationofinfluenzaavirusmrnalevelsbypromotermutations AT garciasastrea attenuationofinfluenzaavirusmrnalevelsbypromotermutations |