Functional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex gene
Naturally occurring mutations in Human T-cell Leukemia Virus Type 1 (HTLV-1) Tax protein lead to loss of recognition by cytotoxic T-lymphocytes. Most of these mutations also abolish or severely impair the transactivation function of Tax. Ninety percent of the <em>Rex</em> gene, which enc...
| Autori principali: | , , , , |
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| Natura: | Journal article |
| Lingua: | English |
| Pubblicazione: |
Elsevier
1997
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| Soggetti: |
| _version_ | 1826261955433725952 |
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| author | Smith, R Niewiesk, S Booth, S Bangham, C Daenke, S |
| author_facet | Smith, R Niewiesk, S Booth, S Bangham, C Daenke, S |
| author_sort | Smith, R |
| collection | OXFORD |
| description | Naturally occurring mutations in Human T-cell Leukemia Virus Type 1 (HTLV-1) Tax protein lead to loss of recognition by cytotoxic T-lymphocytes. Most of these mutations also abolish or severely impair the transactivation function of Tax. Ninety percent of the <em>Rex</em> gene, which encodes the viral regulator of mRNA splicing (Rex), overlaps with the<em>Tax</em> gene. In this paper, we report that four previously described point mutations in <em>Tax</em> that abolished CTL recognition and activity did not alter either the dimerisation function or the ability to export viral mRNA of the corresponding Rex proteins. Rex proteins containing two other amino acid changes were likewise functional. However, five Rex deletion mutants, predominantly but not exclusively found in HAM/TSP patients, had all lost these functions. We conclude that, although the Tax protein is subject to strong CTL-mediated selection, there are stronger functional constraints on amino acid variation in Rex. This may limit the variation in the <em>Tax/Rex</em> nucleotide sequence which results in immune evasion. |
| first_indexed | 2024-03-06T19:28:43Z |
| format | Journal article |
| id | oxford-uuid:1cb4fdb3-e64e-4620-a99e-24d676b08067 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:28:43Z |
| publishDate | 1997 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:1cb4fdb3-e64e-4620-a99e-24d676b080672022-03-26T11:07:00ZFunctional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex geneJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1cb4fdb3-e64e-4620-a99e-24d676b08067Genetics (medical sciences)EnglishOxford University Research Archive - ValetElsevier1997Smith, RNiewiesk, SBooth, SBangham, CDaenke, SNaturally occurring mutations in Human T-cell Leukemia Virus Type 1 (HTLV-1) Tax protein lead to loss of recognition by cytotoxic T-lymphocytes. Most of these mutations also abolish or severely impair the transactivation function of Tax. Ninety percent of the <em>Rex</em> gene, which encodes the viral regulator of mRNA splicing (Rex), overlaps with the<em>Tax</em> gene. In this paper, we report that four previously described point mutations in <em>Tax</em> that abolished CTL recognition and activity did not alter either the dimerisation function or the ability to export viral mRNA of the corresponding Rex proteins. Rex proteins containing two other amino acid changes were likewise functional. However, five Rex deletion mutants, predominantly but not exclusively found in HAM/TSP patients, had all lost these functions. We conclude that, although the Tax protein is subject to strong CTL-mediated selection, there are stronger functional constraints on amino acid variation in Rex. This may limit the variation in the <em>Tax/Rex</em> nucleotide sequence which results in immune evasion. |
| spellingShingle | Genetics (medical sciences) Smith, R Niewiesk, S Booth, S Bangham, C Daenke, S Functional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex gene |
| title | Functional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex gene |
| title_full | Functional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex gene |
| title_fullStr | Functional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex gene |
| title_full_unstemmed | Functional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex gene |
| title_short | Functional conservation of HTLV-1 Rex balances the immune pressure for sequence variation in the Rex gene |
| title_sort | functional conservation of htlv 1 rex balances the immune pressure for sequence variation in the rex gene |
| topic | Genetics (medical sciences) |
| work_keys_str_mv | AT smithr functionalconservationofhtlv1rexbalancestheimmunepressureforsequencevariationintherexgene AT niewiesks functionalconservationofhtlv1rexbalancestheimmunepressureforsequencevariationintherexgene AT booths functionalconservationofhtlv1rexbalancestheimmunepressureforsequencevariationintherexgene AT banghamc functionalconservationofhtlv1rexbalancestheimmunepressureforsequencevariationintherexgene AT daenkes functionalconservationofhtlv1rexbalancestheimmunepressureforsequencevariationintherexgene |