BACKGROUND: Given the overlap between envelope and polymerase in the hepatitis B virus (HBV) genome, changes in antigenic sites of the HBV surface antigen may occur as a result of selection of drug-resistance mutations. METHODS: Serum HBV-DNA was isolated from 71 patients with chronic hepatitis B receiving anti-HBV drugs for longer than 12 months, 52 of whom were HIV-positive. The reverse transcriptase/envelope gene from each HBV isolate was amplified using a nested polymerase chain reaction (PCR) covering 720 bp (aa 48 to 288), which includes all known nucleos(t)ide analogue resistance mutations in HBV. RESULTS: All but 13 patients had received lamivudine. Of the rest, 10 HBV-monoinfected subjects had received adefovir and 3 HBV/HIV-coinfected patients had been treated with tenofovir. Only lamivudine-resistance-associated mutations produced changes in the HBV envelope antigenic sites. Lamivudine resistance mutations were more frequent in HBV genotype A than D (P = 0.014). Contrary to monoinfected individuals, HBV genotype A was the predominant genotype among HBV/HIV-coinfected patients. The triple-HBV mutant rtV173L + rtL180M + rtM204V, which has been shown to produce a diminished hepatitis B surface (HBs) antigen-antibody binding, was found in 3 individuals, all coinfected with HIV and HBV. CONCLUSION: Circulation of HBV encoding envelope mutations with diminished HBs antigen-antibody binding as result of selection of drug-resistance mutations may occur, particularly in patients infected with HBV genotype A, the most prevalent genotype among HBV/HIV-coinfected patients. Such mutations might represent a public health concern because of the potential risk of transmission of HBV drug- and vaccine-resistant strains.
BACKGROUND: Given the overlap between envelope and polymerase in the hepatitis B virus (HBV) genome, changes in antigenic sites of the HBV surface antigen may occur as a result of selection of drug-resistance mutations. METHODS: Serum HBV-DNA was isolated from 71 patients with chronic hepatitis B receiving anti-HBV drugs for longer than 12 months, 52 of whom were HIV-positive. The reverse transcriptase/envelope gene from each HBV isolate was amplified using a nested polymerase chain reaction (PCR) covering 720 bp (aa 48 to 288), which includes all known nucleos(t)ide analogue resistance mutations in HBV. RESULTS: All but 13 patients had received lamivudine. Of the rest, 10 HBV-monoinfected subjects had received adefovir and 3 HBV/HIV-coinfectedpatients had been treated with tenofovir. Only lamivudine-resistance-associated mutations produced changes in the HBV envelope antigenic sites. Lamivudine resistance mutations were more frequent in HBV genotype A than D (P = 0.014). Contrary to monoinfected individuals, HBV genotype A was the predominant genotype among HBV/HIV-coinfectedpatients. The triple-HBV mutant rtV173L + rtL180M + rtM204V, which has been shown to produce a diminished hepatitis B surface (HBs) antigen-antibody binding, was found in 3 individuals, all coinfected with HIV and HBV. CONCLUSION: Circulation of HBV encoding envelope mutations with diminished HBs antigen-antibody binding as result of selection of drug-resistance mutations may occur, particularly in patients infected with HBV genotype A, the most prevalent genotype among HBV/HIV-coinfectedpatients. Such mutations might represent a public health concern because of the potential risk of transmission of HBV drug- and vaccine-resistant strains.
Authors: Eleftherios Michailidis; Karen A Kirby; Atsuko Hachiya; Wangdon Yoo; Sun Pyo Hong; Soo-Ok Kim; William R Folk; Stefan G Sarafianos Journal: Int J Biochem Cell Biol Date: 2012-04-16 Impact factor: 5.085
Authors: Laura Rivino; Nina Le Bert; Upkar S Gill; Kamini Kunasegaran; Yang Cheng; Damien Zm Tan; Etienne Becht; Navjyot K Hansi; Graham R Foster; Tung-Hung Su; Tai-Chung Tseng; Seng Gee Lim; Jia-Horng Kao; Evan W Newell; Patrick Tf Kennedy; Antonio Bertoletti Journal: J Clin Invest Date: 2018-01-08 Impact factor: 14.808
Authors: C John Clements; Ben Coghlan; Mick Creati; Stephen Locarnini; Richard S Tedder; Joseph Torresi Journal: Bull World Health Organ Date: 2009-10-23 Impact factor: 9.408
Authors: Frank Maldarelli; Mary Kearney; Sarah Palmer; Robert Stephens; JoAnn Mican; Michael A Polis; Richard T Davey; Joseph Kovacs; Wei Shao; Diane Rock-Kress; Julia A Metcalf; Catherine Rehm; Sarah E Greer; Daniel L Lucey; Kristen Danley; Harvey Alter; John W Mellors; John M Coffin Journal: J Virol Date: 2013-05-15 Impact factor: 5.103