Molecular virological mechanism of the mother-to-child transmission of hepatitis B virus

Yarong SONG; Jie WANG; Jie LI

doi:10.12449/JCH241107

Volume 40 Issue 11

Nov. 2024

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Article Navigation > Journal of Clinical Hepatology > 2024 > 40(11): 2168-2172

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Molecular virological mechanism of the mother-to-child transmission of hepatitis B virus

DOI: 10.12449/JCH241107

Yarong SONG,
Jie WANG^{,
,},
Jie LI^{,
,}

Department of Microbiology & Infectious Disease Center，School of Basic Medical Sciences，Peking University Health Science Center，Beijing 100191，China

Research funding:

National Key Research and Development Program of China (2023YFC2306902);

National Natural Science Foundation of China (82172251)

More Information

Corresponding author: WANG Jie， wangjie2015@hsc.pku.edu.cn （ORCID： 0000-0001-6518-948X）; LI Jie， jieli@hsc.pku.edu.cn （ORCID： 0000-0001-7864-0460）
Received Date: 2024-08-28
Accepted Date: 2024-09-30
Published Date: 2024-11-25

Abstract

Abstract

Chronic hepatitis B virus （HBV） infection is a major global public health threat. In areas with moderate to high prevalence of HBV， mother-to-child transmission （MTCT） remains the main source of chronic HBV infection. With the application of combined immunization of hepatitis B vaccine and hepatitis B immunoglobulin in neonates， there has been a significant reduction in the incidence rate of HBV MTCT， but there is still a high risk of HBV MTCT in infants born to mothers with positive HBeAg and high viral loads. Although antiviral therapy for pregnant women with high HBV viral loads in late pregnancy can further reduce the risk of HBV MTCT， it is still difficult to completely block HBV MTCT. A deep understanding of the molecular virological mechanisms of HBV MTCT can provide clear ideas for blocking HBV MTCT， which is of great significance for the prevention and management of HBV MTCT.
- Hepatitis B Virus,
- Infectious Disease Transmission， Vertical,
- Genotype

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References(52)

References

[1]	World Health Organization. Global hepatitis report 2024[R]. Geneva: World Health Organization, 2024.
[2]	Chinese Society of Hepatology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B[J]. Chin J Infect Dis, 2023, 41( 1): 3- 28. DOI: 10.3760/cma.j.cn311365-20230220-00050. 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2022年版)[J]. 中华传染病杂志, 2023, 41( 1): 3- 28. DOI: 10.3760/cma.j.cn311365-20230220-00050.
[3]	SMFM, DIONNE-ODOM J, TITA AT, et al.#38: Hepatitis B in pregnancy screening, treatment, and prevention of vertical transmission[J]. Am J Obstet Gynecol, 2016, 214( 1): 6- 14. DOI: 10.1016/j.ajog.2015.09.100.
[4]	CUI FQ, SHEN LP, LI L, et al. Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China[J]. Emerg Infect Dis, 2017, 23( 5): 765- 772. DOI: 10.3201/eid2305.161477.
[5]	CHEN HL, WEN WH, CHANG MH. Management of pregnant women and children: focusing on preventing mother-to-infant transmission[J]. J Infect Dis, 2017, 216( suppl_8): S785- S791. DOI: 10.1093/infdis/jix429.
[6]	LU Y, ZHU FC, LIU JX, et al. The maternal viral threshold for antiviral prophylaxis of perinatal hepatitis B virus transmission in settings with limited resources: A large prospective cohort study in China[J]. Vaccine, 2017, 35( 48 Pt B): 6627- 6633. DOI: 10.1016/j.vaccine.2017.10.032.
[7]	PAN CQ, DUAN ZP, DAI EH, et al. Tenofovir to prevent hepatitis B transmission in mothers with high viral load[J]. N Engl J Med, 2016, 374( 24): 2324- 2334. DOI: 10.1056/NEJMoa1508660.
[8]	GREENUP AJ, TAN PK, NGUYEN V, et al. Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of hepatitis B virus[J]. J Hepatol, 2014, 61( 3): 502- 507. DOI: 10.1016/j.jhep.2014.04.038.
[9]	HAN GR, CAO MK, ZHAO W, et al. A prospective and open-label study for the efficacy and safety of telbivudine in pregnancy for the prevention of perinatal transmission of hepatitis B virus infection[J]. J Hepatol, 2011, 55( 6): 1215- 1221. DOI: 10.1016/j.jhep.2011.02.032.
[10]	World Health Organization. Global health sector strategy on viral hepatitis 2016-2021[R]. Geneva: World Health Organization, 2016.
[11]	MCNAUGHTON AL, D’ARIENZO V, ANSARI MA, et al. Insights from deep sequencing of the HBV genome-unique, tiny, and misunderstood[J]. Gastroenterology, 2019, 156( 2): 384- 399. DOI: 10.1053/j.gastro.2018.07.058.
[12]	DUMPIS U, HOLMES EC, MENDY M, et al. Transmission of hepatitis B virus infection in Gambian families revealed by phylogenetic analysis[J]. J Hepatol, 2001, 35( 1): 99- 104. DOI: 10.1016/s0168-8278(01)00064-2.
[13]	HSU HY, CHEN HL, CHIANG CL, et al. Characterization of hepatitis B virus in tenofovir-treated and untreated chronically infected mothers and their immunoprophylaxis failure infants[J]. Clin Infect Dis, 2023, 76( 3): e783- e790. DOI: 10.1093/cid/ciac539.
[14]	WANG J, LI J, ZHUANG H, et al. Interruption failure of heptitis B virus vaccination in mother-to-infant transmission and heptitis B virus genotypes and preC/BCP mutations[J]. Chin J Epidemiol, 2007, 28( 4): 331- 333. 王佳, 李杰, 庄辉, 等. 乙型肝炎病毒基因型和前C及基本核心启动子突变与乙型肝炎疫苗阻断母婴传播的关系[J]. 中华流行病学杂志, 2007, 28( 4): 331- 333.
[15]	TAKANO T, TAJIRI H, HOSONO S, et al. Natural history of chronic hepatitis B virus infection in children in Japan: A comparison of mother-to-child transmission with horizontal transmission[J]. J Gastroenterol, 2017, 52( 9): 1041- 1050. DOI: 10.1007/s00535-017-1315-4.
[16]	INUI A, KOMATSU H, SOGO T, et al. Hepatitis B virus genotypes in children and adolescents in Japan: Before and after immunization for the prevention of mother to infant transmission of hepatitis B virus[J]. J Med Virol, 2007, 79( 6): 670- 675. DOI: 10.1002/jmv.20884.
[17]	MENDY M, D’MELLO F, KANELLOS T, et al. Envelope protein variability among HBV-Infected asymptomatic carriers and immunized children with breakthrough infections[J]. J Med Virol, 2008, 80( 9): 1537- 1546. DOI: 10.1002/jmv.21221.
[18]	DOMINGO E, PERALES C. Viral quasispecies[J]. PLoS Genet, 2019, 15( 10): e1008271. DOI: 10.1371/journal.pgen.1008271.
[19]	LI Y, XIAO YW, LI LL, et al. The dynamic changes of HBV quasispecies diversity in infancy after immunoprophylaxis failure: A prospective cohort study[J]. Virol J, 2021, 18( 1): 236. DOI: 10.1186/s12985-021-01707-9.
[20]	YANG GF, LIU ZH, YANG JC, et al. Quasispecies characteristics in mother-to-child transmission of hepatitis B virus by next-generation sequencing[J]. J Infect, 2017, 75( 1): 48- 58. DOI: 10.1016/j.jinf.2017.04.012.
[21]	WU QX, XU C, LI JN, et al. Evolution and mutations of hepatitis B virus quasispecies in genotype B and C during vertical transmission[J]. J Med Virol, 2016, 88( 6): 1018- 1026. DOI: 10.1002/jmv.24424.
[22]	LIU F, YU DM, HUANG SY, et al. Clinical implications of evolutionary patterns of homologous, full-length hepatitis B virus quasispecies in different hosts after perinatal infection[J]. J Clin Microbiol, 2014, 52( 5): 1556- 1565. DOI: 10.1128/JCM.03338-13.
[23]	WANG X, DENG WY, QIAN KL, et al. Quasispecies characters of hepatitis B virus in immunoprophylaxis failure infants[J]. Eur J Clin Microbiol Infect Dis, 2018, 37( 6): 1153- 1162. DOI: 10.1007/s10096-018-3235-5.
[24]	WILLI Y, VAN BUSKIRK J, HOFFMANN AA. Limits to the adaptive potential of small populations[J]. Annu Rev Ecol Evol Syst, 2006, 37: 433- 458.
[25]	EIGEN M. Error catastrophe and antiviral strategy[J]. Proc Natl Acad Sci USA, 2002, 99( 21): 13374- 13376. DOI: 10.1073/pnas.212514799.
[26]	XIAO YW, SUN KX, DUAN ZP, et al. Quasispecies characteristic in“a” determinant region is a potential predictor for the risk of immunoprophylaxis failure of mother-to-child-transmission of sub-genotype C2 hepatitis B virus: A prospective nested case-control study[J]. Gut, 2020, 69( 5): 933- 941. DOI: 10.1136/gutjnl-2019-318278.
[27]	LI Y, SONG YR, XIAO YW, et al. The characteristic of HBV quasispecies is related to occult HBV infection of infants born to highly viremic mothers[J]. Viruses, 2024, 16( 7): 1104. DOI: 10.3390/v16071104.
[28]	COOREMAN MP, Van ROOSMALEN MH, MORSCHE R TE, et al. Characterization of the reactivity pattern of murine monoclonal antibodies against wild-type hepatitis B surface antigen to G145R and other naturally occurring“a” loop escape mutations[J]. Hepatology, 1999, 30( 5): 1287- 1292. DOI: 10.1002/hep.510300508.
[29]	KALININA T, IWANSKI A, WILL H, et al. Deficiency in virion secretion and decreased stability of the hepatitis B virus immune escape mutant G145R[J]. Hepatology, 2003, 38( 5): 1274- 1281. DOI: 10.1053/jhep.2003.50484.
[30]	KANG YY, LI FH, GUO HY, et al. Amino acid substitutions Q129N and T131N/M133T in hepatitis B surface antigen(HBsAg) interfere with the immunogenicity of the corresponding HBsAg or viral replication ability[J]. Virus Res, 2018, 257: 33- 39. DOI: 10.1016/j.virusres.2018.08.019.
[31]	ZIAEE M, JAVANMARD D, SHARIFZADEH G, et al. Genotyping and mutation pattern in the overlapping MHR region of HBV isolates in southern Khorasan, Eastern Iran[J]. Hepat Mon, 2016, 16( 10): e37806. DOI: 10.5812/hepatmon.37806.
[32]	YIN WJ, SHEN LP, WANG FZ, et al. Hepatitis B immunoprophylactic failure and characteristics of the hepatitis B virus gene in mother-infant pairs in parts of China[J]. Biomed Environ Sci, 2016, 29( 11): 790- 801. DOI: 10.3967/bes2016.106.
[33]	KWEI K, TANG XL, LOK AS, et al. Impaired virion secretion by hepatitis B virus immune escape mutants and its rescue by wild-type envelope proteins or a second-site mutation[J]. J Virol, 2013, 87( 4): 2352- 2357. DOI: 10.1128/JVI.02701-12.
[34]	YE Q, SHANG SQ, LI W. A new vaccine escape mutant of hepatitis B virus causes occult infection[J]. Hum Vaccin Immunother, 2015, 11( 2): 407- 410. DOI: 10.4161/21645515.2014.994461.
[35]	LARRALDE O, DOW B, JARVIS L, et al. Hepatitis B escape mutants in Scottish blood donors[J]. Med Microbiol Immunol, 2013, 202( 3): 207- 214. DOI: 10.1007/s00430-012-0283-9.
[36]	CHONG-JIN O, NING CW, SHIUAN K, et al. Identification of hepatitis B surface antigen variants with alterations outside the“a” determinant in immunized Singapore infants[J]. J Infect Dis, 1999, 179( 1): 259- 263. DOI: 10.1086/314553.
[37]	WU CC, ZHANG XY, TIAN YJ, et al. Biological significance of amino acid substitutions in hepatitis B surface antigen(HBsAg) for glycosylation, secretion, antigenicity and immunogenicity of HBsAg and hepatitis B virus replication[J]. J Gen Virol, 2010, 91( Pt 2): 483- 492. DOI: 10.1099/vir.0.012740-0.
[38]	LIN YM, JOW GM, MU SC, et al. Naturally occurring hepatitis B virus B-cell and T-cell epitope mutants in hepatitis B vaccinated children[J]. Sci World J, 2013, 2013: 571875. DOI: 10.1155/2013/571875.
[39]	QIN Y, LIAO P. Hepatitis B virus vaccine breakthrough infection: Surveillance of S gene mutants of HBV[J]. Acta Virol, 2018, 62( 2): 115- 121. DOI: 10.4149/av_2018_210.
[40]	CANDOTTI D, DANSO K, ALLAIN JP. Maternofetal transmission of hepatitis B virus genotype E in Ghana, west Africa[J]. J Gen Virol, 2007, 88( Pt 10): 2686- 2695. DOI: 10.1099/vir.0.83102-0.
[41]	ZHAO TJ, YANG ZQ, LI YD, et al. Relationship between C genotype HBV mutation and intrauterine transmission[J]. Chin J Epidemiol, 2021, 42( 4): 716- 722. DOI: 10.3760/cma.j.cn112338-20200915-01163. 赵甜静, 杨志清, 李雁笛, 等. C基因型HBV变异与宫内传播的关系[J]. 中华流行病学杂志, 2021, 42( 4): 716- 722. DOI: 10.3760/cma.j.cn112338-20200915-01163.
[42]	SA-NGUANMOO P, TANGKIJVANICH P, THARMAPHORNPILAS P, et al. Molecular analysis of hepatitis B virus associated with vaccine failure in infants and mothers: A case-control study in Thailand[J]. J Med Virol, 2012, 84( 8): 1177- 1185. DOI: 10.1002/jmv.23260.
[43]	HUANG Y, WANG B, PENG Z, et al. Hepatitis B virus surface gene mutants in immunoprophylaxis-failed infants from Southern China[J]. J Med Virol, 2019, 91( 6): 1069- 1075. DOI: 10.1002/jmv.25430.
[44]	LIU SL, DONG Y, ZHANG L, et al. Influence of HBV gene heterogeneity on the failure of immunization with HBV vaccines in Eastern China[J]. Arch Virol, 2009, 154( 3): 437- 443. DOI: 10.1007/s00705-009-0315-y.
[45]	LIU MM, SONG YR, LI Y, et al. C2729T mutation associated with HBV mother-to-child transmission reduces HBV production via suppressing LHBs expression[J]. Virulence, 2023, 14( 1): 2189676. DOI: 10.1080/21505594.2023.2189676.
[46]	LU JF, LI JE, LIU YL, et al. Relationship between HBV pre-C/BCP mutation/quasispecies and HBeAg and HBV DNA in HBeAg positive patients with chronic hepatitis B[J/CD]. Chin J Exp Clin Infect Dis. 2020, 14( 4): 278- 283. DOI: 10.3877/cma.j.issn.1674-1358.2020.04.003 鲁俊锋, 李金娥, 柳雅立, 等. HBeAg阳性慢性乙型肝炎患者HBV前C/BCP突变/准种与HBeAg和HBV DNA的关系[J/CD]. 中华实验和临床感染病杂志(电子版), 2020, 14( 4): 278- 283. DOI: 10.3877/cma.j.issn.1674-1358.2020.04.003.
[47]	LI J, BUCKWOLD VE, HON MW, et al. Mechanism of suppression of hepatitis B virus precore RNA transcription by a frequent double mutation[J]. J Virol, 1999, 73( 2): 1239- 1244. DOI: 10.1128/JVI.73.2.1239-1244.1999.
[48]	PAREKH S, ZOULIM F, AHN SH, et al. Genome replication, virion secretion, and e antigen expression of naturally occurring hepatitis B virus core promoter mutants[J]. J Virol, 2003, 77( 12): 6601- 6612. DOI: 10.1128/jvi.77.12.6601-6612.2003.
[49]	JAMMEH S, TAVNER F, WATSON R, et al. Effect of basal core promoter and pre-core mutations on hepatitis B virus replication[J]. J Gen Virol, 2008, 89( Pt 4): 901- 909. DOI: 10.1099/vir.0.83468-0.
[50]	CHENG H, SU HX, WANG SP, et al. Association between genomic heterogeneity of hepatitis B virus and intrauterine infection[J]. Virology, 2009, 387( 1): 168- 175. DOI: 10.1016/j.virol.2009.02.015.
[51]	LUCIFORA J, ARZBERGER S, DURANTEL D, et al. Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection[J]. J Hepatol, 2011, 55( 5): 996- 1003. DOI: 10.1016/j.jhep.2011.02.015.
[52]	SONG YR, LU Y, LI Y, et al. HBx 128-133 deletion affecting HBV mother-to-child transmission weakens HBV replication via reducing HBx level and CP/ENII transcriptional activity[J]. Viruses, 2022, 14( 9): 1887. DOI: 10.3390/v14091887.

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