PMID- 31398372 OWN - NLM STAT- MEDLINE DCOM- 20200727 LR - 20200727 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 170 DP - 2019 Oct TI - Investigation of hepatitis B virus (HBV) rtS78T/sC69* mutation in a large cohort of chronic HBV-infected patients with nucleoside/nucleotide analogue treatment. PG - 104579 LID - S0166-3542(19)30239-6 [pii] LID - 10.1016/j.antiviral.2019.104579 [doi] AB - This study aimed to investigate clinical occurrence and significance of the rtS78T/sC69* mutation of hepatitis B virus (HBV). A total of 22,009 consecutive chronic HBV-infected patients who underwent resistance testing at the Fifth Medical Center of Chinese PLA General Hospital (Original name Beijing 302 Hospital) from 2007 to 2016 were enrolled. Serum samples were collected for sequence analysis of HBV reverse-transcriptase (RT) and S regions. Phenotypic analysis was performed to evaluate the viral replication capacity and drug susceptibility. The rtS78T mutation was detected in 0.83% (182/22,009) of the patients' samples. All mutations simultaneously created a stop codon at sC69 (sC69*). The prevalence of rtS78T/sC69* did not differ significantly between the patients with and without entecavir/tenofovir treatment. Of the 182 mutation-positive samples, 41 (22.5%) were detected with signature drug-resistance mutations to adefovir (n = 26), lamivudine (n = 11), entecavir (n = 3), and lamivudine plus adefovir (n = 1). The HBV DNA and RNA levels of the rtS78T/sC69* mutant were significantly increased compared to the wild-type; while the mutant had undetectable secreted and intracellular HBsAg, and its half maximal effective concentration to lamivudine, adefovir, entecavir, and tenofovir were 3.73-, 1.61-, 4.76-, and 3.71-fold of the wild-type, respectively. Artificial elimination of the rtS78T mutation had a limited effect on the drug susceptibilities. The data obtained in the present study suggested that the emergence of the rtS78T/sC69* mutation was not closely related to entecavir/tenofovir treatment and itself appeared insufficient to confer drug resistance unless it coexisted with signature drug-resistance mutations. CI - Copyright (c) 2019 Elsevier B.V. All rights reserved. FAU - Luo, Dan AU - Luo D AD - Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China; Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Liu, Yan AU - Liu Y AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Chen, Rongjuan AU - Chen R AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Niu, Ming AU - Niu M AD - Institute of Chinese Medicine, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Liu, Lujie AU - Liu L AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Li, Xiaodong AU - Li X AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Li, Qi AU - Li Q AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Huang, Bixia AU - Huang B AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Wang, Jun AU - Wang J AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. FAU - Xu, Dongping AU - Xu D AD - Institute of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital (Beijing 302 Hospital), Beijing, 100039, China. Electronic address: xudongping302@sina.com. FAU - Lin, Shumei AU - Lin S AD - Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: linshumei123@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190806 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antiviral Agents) RN - 0 (DNA, Viral) RN - 0 (Nucleosides) RN - 0 (Viral Proteins) RN - 5968Y6H45M (entecavir) RN - 5Z93L87A1R (Guanine) RN - 99YXE507IL (Tenofovir) RN - EC 2.7.7.49 (RNA-Directed DNA Polymerase) SB - IM MH - Adult MH - Antiviral Agents/*therapeutic use MH - Cohort Studies MH - DNA, Viral MH - Drug Resistance, Multiple, Viral/genetics MH - Female MH - Genotype MH - Guanine/analogs & derivatives/therapeutic use MH - Hepatitis B virus/drug effects/*genetics MH - Hepatitis B, Chronic/*drug therapy/*virology MH - Humans MH - Male MH - Middle Aged MH - *Mutation MH - Nucleosides/therapeutic use MH - RNA-Directed DNA Polymerase/genetics MH - Tenofovir/therapeutic use MH - Viral Proteins/genetics OTO - NOTNLM OT - Drug resistance OT - Entecavir OT - Hepatitis B virus OT - Mutation OT - Tenofovir OT - rtS78T/sC69* EDAT- 2019/08/10 06:00 MHDA- 2020/07/28 06:00 CRDT- 2019/08/10 06:00 PHST- 2019/04/27 00:00 [received] PHST- 2019/07/29 00:00 [revised] PHST- 2019/08/05 00:00 [accepted] PHST- 2019/08/10 06:00 [pubmed] PHST- 2020/07/28 06:00 [medline] PHST- 2019/08/10 06:00 [entrez] AID - S0166-3542(19)30239-6 [pii] AID - 10.1016/j.antiviral.2019.104579 [doi] PST - ppublish SO - Antiviral Res. 2019 Oct;170:104579. doi: 10.1016/j.antiviral.2019.104579. Epub 2019 Aug 6.