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本帖最后由 风雨不动 于 2012-4-14 14:55 编辑
<http://www.dldjournalonline.com/article/PIIS1590865811002544/abstract?rss=yes>
Digestive and Liver Disease
Article in Press
Role of hepatitis B virus genetic barrier in drug-resistance and
immune-escape development
Valentina Svicher, et.al(CUT)
Received 15 March 2011; accepted 1 July 2011. published online 10 August
2011. Corrected Proof
Abstract
Background
Impact of hepatitis B virus genetic barrier, defined as the number and type
of nucleotide substitutions required to overcome drug/immune selective
pressure, on drug-resistance/immune-escape development is unknown.
Methods
Genetic barrier was calculated according to Van de Vijver (2006) in 3482
hepatitis B virus-reverse transcriptase/HBV surface antigen sequences from
555 drug-naïve patients and 2927 antiviral-treated patients infected with
hepatitis B virus genotypes A-G.
Results
Despite high natural variability, genetic barrier for drug-resistance
development is identical amongst hepatitis B virus genotypes, but varies
according to drug-resistance mutation type. Highest genetic barrier is
found for secondary/compensatory mutations (e.g.
rtL80I/V–rtL180M–rtV173L), whilst most primary mutations (including
rtM204V–rtA181T/V–rtI169T–rtA194T) are associated with low genetic
barrier. An exception is rtM204I, which can derive from a transition or a
transversion. Genotypes A and G are more prone to develop
immune/diagnostic-escape mutations sT114R and sG130N. Vaccine-escape
associated sT131N-mutation is a natural polymorphism in both A and G
genotypes.
Conclusion
Genetic barrier and reverse transcriptase/HBV surface antigen overlapping
can synergistically influence hepatitis B virus
drug-resistance/immune-escape development. The different immune-escape
potential of specific hepatitis B virus genotypes could have important
clinical consequences in terms of disease progression, vaccine strategies
and correct HBV surface antigen detection.
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发表于 2011-8-17 15:49
