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Sci Rep. 2017 Aug 31;7(1):10168. doi: 10.1038/s41598-017-10591-9.

Quantifying perinatal transmission of Hepatitis B viral quasispecies by tag linkage deep sequencing.

Du Y1,2, Chi X3,4,5, Wang C3, Jiang J6, Kong F3, Yan H3, Wang X3,4,5, Li J7, Wu NC1,8, Dai L1,9, Zhang TH1,10, Shu S1, Zhou J11, Yoshizawa JM11, Li X11, Bhattacharya D12, Wu TT1, Niu J13,14,15, Sun R16,17,18.

Author information

1
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA.
2
Cancer Institute, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
3
Hepatology, The 1st hospital of Jilin University, Changchun, 130031, China.
4
Key laboratory of Zoonosis Research, Ministry Education, Jilin University, Changchun, 130062, China.
5
Key Laboratory of Infectious Disease, Laboratory of Molecular Virology, Changchun, 130021, China.
6
Epidemiology, The 1st hospital of Jilin University, Changchun, 130031, China.
7
Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
8
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.
9
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, 90095, USA.
10
Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA.
11
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
12
Department of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
13
Hepatology, The 1st hospital of Jilin University, Changchun, 130031, China. junqiniu@aliyun.com.
14
Key laboratory of Zoonosis Research, Ministry Education, Jilin University, Changchun, 130062, China. junqiniu@aliyun.com.
15
Key Laboratory of Infectious Disease, Laboratory of Molecular Virology, Changchun, 130021, China. junqiniu@aliyun.com.
16
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, 90095, USA. rsun@mednet.ucla.edu.
17
Cancer Institute, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, Zhejiang University, Hangzhou, 310058, China. rsun@mednet.ucla.edu.
18
Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA, 90095, USA. rsun@mednet.ucla.edu.

Abstract

Despite full immunoprophylaxis, mother-to-child transmission (MTCT) of Hepatitis B Virus still occurs in approximately 2-5% of HBsAg positive mothers. Little is known about the bottleneck of HBV transmission and the evolution of viral quasispecies in the context of MTCT. Here we adopted a newly developed tag linkage deep sequencing method and analyzed the quasispecies of four MTCT pairs that broke through immunoprophylaxis. By assigning unique tags to individual viral sequences, we accurately reconstructed HBV haplotypes in a region of 836 bp, which contains the major immune epitopes and drug resistance mutations. The detection limit of minor viral haplotypes reached 0.1% for individual patient sample. Dominance of "a determinant" polymorphisms were observed in two children, which pre-existed as minor quasispecies in maternal samples. In all four pairs of MTCT samples, we consistently observed a significant overlap of viral haplotypes shared between mother and child. We also demonstrate that the data can be potentially useful to estimate the bottleneck effect during HBV MTCT, which provides information to optimize treatment for reducing the frequency of MTCT.

PMID:
28860476
PMCID:
PMC5578979
DOI:
10.1038/s41598-017-10591-9
[Indexed for MEDLINE]
Free PMC Article

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