Role of hepatitis B virus genetic barrier in drug-resistance and immune-escape development

[Guest guest]

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.

[Guest guest]

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.