Abstract:
:Hepatitis C virus (HCV) is a variable RNA virus that can readily establish persistent infection. Cellular immune responses are important in the early control of the virus. Evidence from animal models suggests that mutation in epitopes recognized by CD8+ T lymphocytes may play an important role in the establishment of persistence but in human persistent infection, equivalent evidence is lacking. We investigated this by analysing a unique resource: viruses from a set of chronically HCV-infected individuals in whom the CD8+ T-cell responses in liver had previously been accurately mapped. Virus was sequenced in seven individuals at 10 epitopes restricted by 10 human leucocyte antigen (HLA) molecules. Two main patterns emerged: in the majority of epitopes sequenced, no variation was seen. In three epitopes, mutations were identified which were compatible with immune escape as assessed using phylogenetic and/or functional studies. These data suggest that - even where specific intrahepatic T cells are detectable - many epitopes do not undergo mutation in chronic human infection. On the contrary, virus may escape from intrahepatic CD8+ T-cell responses in a 'patchy' manner in certain specific epitopes. Furthermore, longitudinal studies to identify the differences between 'selecting' and 'nonselecting' intrahepatic CD8+ T-cell responses are needed in HCV infection.
journal_name
J Viral Hepatjournal_title
Journal of viral hepatitisauthors
Komatsu H,Lauer G,Pybus OG,Ouchi K,Wong D,Ward S,Walker B,Klenerman Pdoi
10.1111/j.1365-2893.2005.00676.xsubject
Has Abstractpub_date
2006-02-01 00:00:00pages
121-30issue
2eissn
1352-0504issn
1365-2893pii
JVH676journal_volume
13pub_type
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journal_title:Journal of viral hepatitis
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2006-12-01 00:00:00
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更新日期:2021-02-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of viral hepatitis
pub_type: 杂志文章
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更新日期:2001-11-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Journal of viral hepatitis
pub_type: 杂志文章
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