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Arch Virol. 2019 Sep;164(9):2297-2307. doi: 10.1007/s00705-019-04332-8. Epub 2019 Jul 2.

Impact of hepatitis B virus genotype F on in vitro diagnosis: detection efficiency of HBsAg from Amerindian subgenotypes F1b and F4.

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CONICET, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, Buenos Aires, Argentina.
Instituto de Agrobiotecnología y Biología Molecular, INTA-CONICET, Buenos Aires, Argentina.
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús (IIB-INTECH), Universidad Nacional de San Martín (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Departamento de Ciencia y Tecnología, Laboratorio de Ingeniería Genética y Biología Celular y Molecular, Área Virosis de Insectos (LIGBCM-AVI), Instituto de Microbiología Básica y Aplicada (IMBA), Universidad Nacional de Quilmes, Bernal, Provincia de Buenos Aires, Argentina.
Facultad de Farmacia y Bioquímica, Instituto de Nanobiotecnología (NANOBIOTEC), Universidad de Buenos Aires, Buenos Aires, Argentina.
CONICET, Instituto de Investigaciones en Microbiología y Parasitología Médica (IMPaM), Universidad de Buenos Aires, Buenos Aires, Argentina.


The influence of the high genetic variability of hepatitis B virus (HBV) on the sensitivity of serological assays has received little attention so far. A major source of variability is related to viral genotypes and subgenotypes. Their possible influence on diagnosis and prophylaxis is poorly known and has mostly been evaluated for genotypes A, B, C and D. Robust data showing the detection efficiency of HBsAg from genotype F is lacking. This study examined the effect of virus-like particles containing HBsAg from genotypes A and F (particularly, F1b and F4) produced in Pichia pastoris in relation to the anti-HBs antibodies used in the immunoassays for in vitro diagnosis and compared it with that exerted by the G145R S-escape mutant. The results showed that HBsAg detection rates for subgenotypes F1b and F4 differed significantly from those obtained for genotype A and that subgenotype F1b had a major impact on the sensitivity of the immunoassays tested. Prediction of the tertiary structure of subgenotypes F1b and F4 revealed changes inside and outside the major hydrophilic region (aa 101-160) of the HBsAg compared to genotype A and the G145R variant. A phosphorylation site (target for protein kinase C) produced by the G145R substitution might prevent recognition by anti-HBs antibodies. In conclusion, the use of different genotypes or variants for diagnosis could improve the rate of detection of HBV infection. The incorporation of a genotype-F-derived HBsAg vaccine in areas where this genotype is endemic should be evaluated, since this might also affect vaccination efficacy.

[Indexed for MEDLINE]

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