Host and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infection
<p>HCV infects 170 million persons worldwide and is a serious global health problem. Genotype-3a is the dominant genotype in newly diagnosed infections within the UK and has a high response rate to interferon therapy, with up to 70% patients achieving a sustained virological response (SVR). Th...
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| Format: | Thesis |
| Idioma: | English |
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2011
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| _version_ | 1826304066648539136 |
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| author | Humphreys, I Isla S. Humphreys |
| author2 | Barnes, E |
| author_facet | Barnes, E Humphreys, I Isla S. Humphreys |
| author_sort | Humphreys, I |
| collection | OXFORD |
| description | <p>HCV infects 170 million persons worldwide and is a serious global health problem. Genotype-3a is the dominant genotype in newly diagnosed infections within the UK and has a high response rate to interferon therapy, with up to 70% patients achieving a sustained virological response (SVR). The reason(s) for this are unknown; therefore the aim was to assess host and viral factors that determine treatment outcome of subtype-3a infection.</p><p>Full-length subtype-3a viral sequence analysis identified 2 novel regions of hypervariability within E2 - HVR495 and HVR575, that are subject to positive selection pressure. A 5 amino-acid insertion found only in subtype-3a and a putative glycosylation site were contained within HVR575. These data suggest that HVR495 and HVR575 may serve as major antigenic sites in subtype-3a HCV infection. Successful treatment of chronic subtype-3a infection was not associated with pre-treatment quasispecies diversity and complexity, PePHD, HVR495 or HVR575 sequence. Different patterns of quasispecies variation were observed in patients that failed treatment.</p><p>Subtype-3a specific CD8+ T-cell responses in chronic infection target non-structural proteins, in contrast to pre-dominant genotype-1 core-specific CD4+ T-cell responses. SVR was associated with a decline in subtype-3a specific and non-specific T-cell responses, and also total lymphocyte counts, which all recovered after treatment. These data do not support the theory that clearance of subtype-3a is associated with an enhancement of antiviral T-cell responses. Overlapping peptides detected a greater number of subtype-3a T-cell responses compared with peptides representing putative predicted CD8 epitopes. Therefore subtype-3a HCV is distinct from genotype-1 in terms of genome sequence, effect of treatment on quasispecies and subtype-3a specific T-cell responses, further emphasising the importance in understanding this distinct subtype.</p> |
| first_indexed | 2024-03-07T06:12:11Z |
| format | Thesis |
| id | oxford-uuid:efe4f97b-5f82-4e8a-8ed5-18b71c5f00db |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:12:11Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:efe4f97b-5f82-4e8a-8ed5-18b71c5f00db2022-03-27T11:43:39ZHost and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infectionThesishttp://purl.org/coar/resource_type/c_db06uuid:efe4f97b-5f82-4e8a-8ed5-18b71c5f00dbInfectious diseasesBiology (medical sciences)ImmunologyEnglishOxford University Research Archive - Valet2011Humphreys, IIsla S. HumphreysBarnes, E<p>HCV infects 170 million persons worldwide and is a serious global health problem. Genotype-3a is the dominant genotype in newly diagnosed infections within the UK and has a high response rate to interferon therapy, with up to 70% patients achieving a sustained virological response (SVR). The reason(s) for this are unknown; therefore the aim was to assess host and viral factors that determine treatment outcome of subtype-3a infection.</p><p>Full-length subtype-3a viral sequence analysis identified 2 novel regions of hypervariability within E2 - HVR495 and HVR575, that are subject to positive selection pressure. A 5 amino-acid insertion found only in subtype-3a and a putative glycosylation site were contained within HVR575. These data suggest that HVR495 and HVR575 may serve as major antigenic sites in subtype-3a HCV infection. Successful treatment of chronic subtype-3a infection was not associated with pre-treatment quasispecies diversity and complexity, PePHD, HVR495 or HVR575 sequence. Different patterns of quasispecies variation were observed in patients that failed treatment.</p><p>Subtype-3a specific CD8+ T-cell responses in chronic infection target non-structural proteins, in contrast to pre-dominant genotype-1 core-specific CD4+ T-cell responses. SVR was associated with a decline in subtype-3a specific and non-specific T-cell responses, and also total lymphocyte counts, which all recovered after treatment. These data do not support the theory that clearance of subtype-3a is associated with an enhancement of antiviral T-cell responses. Overlapping peptides detected a greater number of subtype-3a T-cell responses compared with peptides representing putative predicted CD8 epitopes. Therefore subtype-3a HCV is distinct from genotype-1 in terms of genome sequence, effect of treatment on quasispecies and subtype-3a specific T-cell responses, further emphasising the importance in understanding this distinct subtype.</p> |
| spellingShingle | Infectious diseases Biology (medical sciences) Immunology Humphreys, I Isla S. Humphreys Host and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infection |
| title | Host and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infection |
| title_full | Host and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infection |
| title_fullStr | Host and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infection |
| title_full_unstemmed | Host and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infection |
| title_short | Host and viral factors that determine the clinical outcome of hepatitis C virus genotype 3a infection |
| title_sort | host and viral factors that determine the clinical outcome of hepatitis c virus genotype 3a infection |
| topic | Infectious diseases Biology (medical sciences) Immunology |
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