New amino acid changes in drug resistance sites and HBsAg in hepatitis B virus genotype H.
Long-term treatment with retrotranscriptase (RT) inhibitors eventually leads to the development of drug resistance. Drug-related mutations occur naturally and these can be found in hepatitis B virus (HBV) carriers who have never received antiviral therapy. HBsAg are overlapped with RT domain, thus nucleot(s)ide analogues (NAs) resistance mutations and naturally-occurring mutations can cause amino acid changes in the HBsAg. Twenty-two patients with chronic hepatitis B were enrolled; three of them were previously treated with NAs and 19 were NAs-naïve treated. HBV reverse transcriptase region was sequenced; genotyping and analysis of missense mutations were performed in both RT domain and HBsAg. There was predominance of genotype H. Drug mutations were present in 18.2% of patients. Classical lamivudine resistance mutations (rtM204V/rtL180M) were present in one naïve-treatment patient infected with genotype G. New amino acid changes were identified in drug resistance sites in HBV strains from patients infected with genotype H; rtQ215E was present in two naïve-NAs treatment patients and rtI169M was identified in a patient previously treated with lamivudine. Mutations at sites rt169, rt204, and rt215 resulted in the Y161C, I195M, and C206W mutations at HBsAg. Also, new amino acid changes were identified in B-cell and T-cell epitopes and were more frequent in HBsAg compared to RT domain. In conclusion, new amino acid changes at antiviral resistance sites, B-cell and T-cell epitopes in HBV genotype H were identified in Mexican patients.
Institute of Molecular Biology in Medicine and Gene Therapy, CUCS, University of Guadalajara, Guadalajara, Jalisco, Mexico.
D A
DA
Fernández-Galindo
F
F
Sánchez-Ávila
L
L
Bobadilla-Morales
P
P
Gómez-Quiróz
M
M
Bueno-Topete
J
J
Armendáriz-Borunda
L V
LV
Sánchez-Orozco
D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult
D000998:Antiviral Agents; D004279:DNA, Viral; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006514:Hepatitis B Surface Antigens; D019259:Lamivudine; D012194:RNA-Directed DNA Polymerase
B-cell epitopes; RT domain; T-cell epitopes; nucleot(s)ide analogues