Infect Genet Evol. 2018 Oct 25;67:17-22. doi: 10.1016/j.meegid.2018.10.017. [Epub ahead of print]
Role of viral load in Hepatitis B virus evolution in persistently normal ALT chronically infected patients.
Gauder C1, Mojsiejczuk LN2, Tadey L3, Mammana L3, Bouzas MB3, Campos RH2, Flichman DM4.
Author information
1
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Junín 956 4to piso, Ciudad Autónoma de Buenos Aires, Argentina.
2
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Junín 956 4to piso, Ciudad Autónoma de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
3
Unidad de Virología Hospital F.J. Muñiz, Uspallata 2272, Ciudad Autónoma de Buenos Aires, Argentina.
4
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Microbiología, Inmunología y Biotecnología, Cátedra de Virología, Junín 956 4to piso, Ciudad Autónoma de Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Electronic address: [email protected].
Abstract
Chronic HBV infection has been associated with severe liver disease although most of them do not progress to this stage. Even though low replicative carriers form the largest group of HBV chronically infected patients, there is a paucity of longitudinal studies to evaluate the molecular evolution of the whole genome in this subset of patients. In this study, longitudinal samples from 10 patients with persistently normal ALT levels were collected. HBV full-length genome sequences were obtained from 3 samples per patient (baseline, 5 and 10-years of follow-up). Patients were grouped according to HBV-DNA level into <103 IU/ml (group A) or > 103 IU/ml (group B). The substitution rate was inversely related with HBV-DNA levels. Moreover, the rate in the 10-year follow-up was significantly higher in group A (6.9 × 10-4 ± 1.3 × 10-4) than group B (2.7 × 10-4 ± 7.4 × 10-5 substitution/site/year, p < .001). Most of the substitutions were in the Core region and the majority were non-synonymous changes. The rate of nucleotide substitution was inversely related to HBV-DNA levels, highlighting the role of viral load in the HBV intra-host dynamics, even in low replicative state patients. Moreover, the difference in the substitution rate between the analysed groups was mainly consequence of substitutions restricted to the Core region, particularly in the simple coding region and antigenic epitopes, which suggest that the immune pressure drives the different evolutionary behaviour of groups.
KEYWORDS:
1
Universidad de Buenos Aires,Facultad de FarmaciayBioquímica,DepartamentodeMicrobiología,InmunologíayBiotecnología,CátedradeVirología,Junín9564to piso,CiudadAutónomadeBuenos Aires,Argentina。
2
Universidad de Buenos Aires,Facultad de FarmaciayBioquímica,DepartamentodeMicrobiología,InmunologíayBiotecnología,CátedradeVirología,Junín9564to piso,CiudadAutónomadeBuenos Aires,Argentina;阿根廷国家调查委员会(CONICET)。
3
UnidaddeVirologíaHospitalF.J.Muñiz,Uspallata 2272,CiudadAutónomadeBuenos Aires,Argentina。
4
Universidad de Buenos Aires,Facultad de FarmaciayBioquímica,DepartamentodeMicrobiología,InmunologíayBiotecnología,CátedradeVirología,Junín9564to piso,CiudadAutónomadeBuenos Aires,Argentina;阿根廷国家调查委员会(CONICET)。电子地址:[email protected]。