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Published in: Virology Journal 1/2016

Open Access 01-12-2016 | Research

Occult hepatitis B virus infection: influence of S protein variants

Authors: Zhenhua Zhang, Ling Zhang, Yu Dai, Yafei Zhang, Jun Li, Xu Li

Published in: Virology Journal | Issue 1/2016

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Abstract

Background

In occult hepatitis B viral infection (OBI), the persistence of hepatitis B virus (HBV) DNA is associated with a lack of hepatitis B surface antigen (HBsAg). To assess the possible role of HBsAg immune escape variants in OBI patients, variability in the HBV S gene was evaluated for OBI patients as well as chronic HBV infection patients from the same families.

Methods

We selected 17 HBV DNA-positive/HBsAg-negative patients (OBI group) and 15 HBV DNA- and HBsAg-positive patients from OBI families (control group). The S gene was amplified and cloned, and at least 15 clones per patient were sequenced and analyzed.

Results

Although the incidence of stop codon mutations within the S region was higher in the OBI group (13.6 %) than in the control group (1.5 %, P < 0.001), this type of mutation, together with insertion and deletion mutations, was prevalent in only three OBI patients. In the major hydrophilic region (MHR), a median of 0.75 residues were altered in every 100 residues for the OBI patients, whereas 0.95 out of 100 residues were changed in the control group (P = 0.428). Furthermore, some variants that are generally considered immune escape variants, such as mutations at positions s145, s147, and s123, were only observed in less than 5 % of all the clones sequenced, in either OBI or control group.

Conclusions

Our data suggest that HBsAg variants may not play a major role in OBI pathogenesis.
Literature
1.
go back to reference Martin CM, Welge JA, Rouster SD, Shata MT, Sherman KE, Blackard JT. Mutations associated with occult hepatitis B virus infection result in decreased surface antigen expression in vitro. J Viral Hepat. 2012;19:716–23.PubMedPubMedCentralCrossRef Martin CM, Welge JA, Rouster SD, Shata MT, Sherman KE, Blackard JT. Mutations associated with occult hepatitis B virus infection result in decreased surface antigen expression in vitro. J Viral Hepat. 2012;19:716–23.PubMedPubMedCentralCrossRef
3.
go back to reference Assar S, Arababadi MK, Ahmadabadi BN, Salehi M, Kennedy D. Occult hepatitis B virus (HBV) infection: a global challenge for medicine. Clin Lab. 2012;58:1225–30.PubMed Assar S, Arababadi MK, Ahmadabadi BN, Salehi M, Kennedy D. Occult hepatitis B virus (HBV) infection: a global challenge for medicine. Clin Lab. 2012;58:1225–30.PubMed
4.
go back to reference Chen WN, Oon CJ. Hepatitis B virus surface antigen (HBsAg) mutants in Singapore adults and vaccinated children with high anti-hepatitis B virus antibody levels but negative for HBsAg. J Clin Microbiol. 2000;38:2793–4.PubMedPubMedCentral Chen WN, Oon CJ. Hepatitis B virus surface antigen (HBsAg) mutants in Singapore adults and vaccinated children with high anti-hepatitis B virus antibody levels but negative for HBsAg. J Clin Microbiol. 2000;38:2793–4.PubMedPubMedCentral
5.
go back to reference Huang X, Hollinger FB. Occult hepatitis B virus infection and hepatocellular carcinoma: a systematic review. J Viral Hepat. 2014;21:153–62.PubMedCrossRef Huang X, Hollinger FB. Occult hepatitis B virus infection and hepatocellular carcinoma: a systematic review. J Viral Hepat. 2014;21:153–62.PubMedCrossRef
6.
go back to reference Shahmoradi S, Yahyapour Y, Mahmoodi M, Alavian SM, Fazeli Z, Jazayeri SM. High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG. J Hepatol. 2012;57:515–21.PubMedCrossRef Shahmoradi S, Yahyapour Y, Mahmoodi M, Alavian SM, Fazeli Z, Jazayeri SM. High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG. J Hepatol. 2012;57:515–21.PubMedCrossRef
7.
go back to reference Mu SC, Lin YM, Jow GM, Chen BF. Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan. J Hepatol. 2009;50:264–72.PubMedCrossRef Mu SC, Lin YM, Jow GM, Chen BF. Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan. J Hepatol. 2009;50:264–72.PubMedCrossRef
8.
go back to reference Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008;49:652–7.PubMedCrossRef Raimondo G, Allain JP, Brunetto MR, Buendia MA, Chen DS, Colombo M, et al. Statements from the Taormina expert meeting on occult hepatitis B virus infection. J Hepatol. 2008;49:652–7.PubMedCrossRef
9.
go back to reference Gerlich WH, Bremer C, Saniewski M, Schuttler CG, Wend UC, Willems WR, et al. Occult hepatitis B virus infection: detection and significance. Dig Dis. 2010;28:116–25.PubMedCrossRef Gerlich WH, Bremer C, Saniewski M, Schuttler CG, Wend UC, Willems WR, et al. Occult hepatitis B virus infection: detection and significance. Dig Dis. 2010;28:116–25.PubMedCrossRef
10.
go back to reference Pollicino T, Squadrito G, Cerenzia G, Cacciola I, Raffa G, Craxi A, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology. 2004;126:102–10.PubMedCrossRef Pollicino T, Squadrito G, Cerenzia G, Cacciola I, Raffa G, Craxi A, et al. Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection. Gastroenterology. 2004;126:102–10.PubMedCrossRef
11.
go back to reference Burns GS, Thompson AJ. Viral hepatitis B: clinical and epidemiological characteristics. Cold Spring Harb Perspect Med. 2014;4:a024935.PubMedCrossRef Burns GS, Thompson AJ. Viral hepatitis B: clinical and epidemiological characteristics. Cold Spring Harb Perspect Med. 2014;4:a024935.PubMedCrossRef
12.
go back to reference Hou J, Wang Z, Cheng J, Lin Y, Lau GK, Sun J, et al. Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen-negative Chinese carriers. Hepatology. 2001;34:1027–34.PubMedCrossRef Hou J, Wang Z, Cheng J, Lin Y, Lau GK, Sun J, et al. Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen-negative Chinese carriers. Hepatology. 2001;34:1027–34.PubMedCrossRef
13.
go back to reference Zaaijer HL, Torres P, Ontanon A, Ponte LG, Koppelman MH, Lelie PN, et al. Multiple surface antigen mutations in five blood donors with occult hepatitis B virus infection. J Med Virol. 2008;80:1344–9.PubMedCrossRef Zaaijer HL, Torres P, Ontanon A, Ponte LG, Koppelman MH, Lelie PN, et al. Multiple surface antigen mutations in five blood donors with occult hepatitis B virus infection. J Med Virol. 2008;80:1344–9.PubMedCrossRef
14.
go back to reference Yuan Q, Ou SH, Chen CR, Ge SX, Pei B, Chen QR, et al. Molecular characteristics of occult hepatitis B virus from blood donors in southeast China. J Clin Microbiol. 2010;48:357–62.PubMedPubMedCentralCrossRef Yuan Q, Ou SH, Chen CR, Ge SX, Pei B, Chen QR, et al. Molecular characteristics of occult hepatitis B virus from blood donors in southeast China. J Clin Microbiol. 2010;48:357–62.PubMedPubMedCentralCrossRef
15.
go back to reference Thedja MD, Roni M, Harahap AR, Siregar NC, Ie SI, Muljono DH. Occult hepatitis B in blood donors in Indonesia: altered antigenicity of the hepatitis B virus surface protein. Hepatol Int. 2010;4:608–14.PubMedPubMedCentralCrossRef Thedja MD, Roni M, Harahap AR, Siregar NC, Ie SI, Muljono DH. Occult hepatitis B in blood donors in Indonesia: altered antigenicity of the hepatitis B virus surface protein. Hepatol Int. 2010;4:608–14.PubMedPubMedCentralCrossRef
16.
go back to reference Svicher V, Cento V, Bernassola M, Neumann-Fraune M, Van Hemert F, Chen M, et al. Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection. Antiviral Res. 2012;93:86–93.PubMedCrossRef Svicher V, Cento V, Bernassola M, Neumann-Fraune M, Van Hemert F, Chen M, et al. Novel HBsAg markers tightly correlate with occult HBV infection and strongly affect HBsAg detection. Antiviral Res. 2012;93:86–93.PubMedCrossRef
17.
go back to reference Jeantet D, Chemin I, Mandrand B, Tran A, Zoulim F, Merle P, et al. Cloning and expression of surface antigens from occult chronic hepatitis B virus infections and their recognition by commercial detection assays. J Med Virol. 2004;73:508–15.PubMedCrossRef Jeantet D, Chemin I, Mandrand B, Tran A, Zoulim F, Merle P, et al. Cloning and expression of surface antigens from occult chronic hepatitis B virus infections and their recognition by commercial detection assays. J Med Virol. 2004;73:508–15.PubMedCrossRef
18.
go back to reference Zhang ZH, Li L, Zhao XP, Glebe D, Bremer CM, Zhang ZM, et al. Elimination of hepatitis B virus surface antigen and appearance of neutralizing antibodies in chronically infected patients without viral clearance. J Viral Hepat. 2011;18:424–33.PubMedCrossRef Zhang ZH, Li L, Zhao XP, Glebe D, Bremer CM, Zhang ZM, et al. Elimination of hepatitis B virus surface antigen and appearance of neutralizing antibodies in chronically infected patients without viral clearance. J Viral Hepat. 2011;18:424–33.PubMedCrossRef
19.
go back to reference Ito K, Qin Y, Guarnieri M, Garcia T, Kwei K, Mizokami M, et al. Impairment of hepatitis B virus virion secretion by single-amino-acid substitutions in the small envelope protein and rescue by a novel glycosylation site. J Virol. 2010;84:12850–61.PubMedPubMedCentralCrossRef Ito K, Qin Y, Guarnieri M, Garcia T, Kwei K, Mizokami M, et al. Impairment of hepatitis B virus virion secretion by single-amino-acid substitutions in the small envelope protein and rescue by a novel glycosylation site. J Virol. 2010;84:12850–61.PubMedPubMedCentralCrossRef
20.
go back to reference Huang CH, Yuan Q, Chen PJ, Zhang YL, Chen CR, Zheng QB, et al. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors. J Hepatol. 2012;57:720–9.PubMedCrossRef Huang CH, Yuan Q, Chen PJ, Zhang YL, Chen CR, Zheng QB, et al. Influence of mutations in hepatitis B virus surface protein on viral antigenicity and phenotype in occult HBV strains from blood donors. J Hepatol. 2012;57:720–9.PubMedCrossRef
21.
go back to reference Kim KH, Chang HY, Park JY, Park ES, Park YK, Han KH, et al. Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers. Clin Mol Hepatol. 2014;20:251–60.PubMedPubMedCentralCrossRef Kim KH, Chang HY, Park JY, Park ES, Park YK, Han KH, et al. Spontaneous HBsAg loss in Korean patients: relevance of viral genotypes, S gene mutations, and covalently closed circular DNA copy numbers. Clin Mol Hepatol. 2014;20:251–60.PubMedPubMedCentralCrossRef
22.
go back to reference Bruni R, Prosperi M, Marcantonio C, Amadori A, Villano U, Tritarelli E, et al. A computational approach to identify point mutations associated with occult hepatitis B: significant mutations affect coding regions but not regulative elements of HBV. Virol J. 2011;8:394.PubMedPubMedCentralCrossRef Bruni R, Prosperi M, Marcantonio C, Amadori A, Villano U, Tritarelli E, et al. A computational approach to identify point mutations associated with occult hepatitis B: significant mutations affect coding regions but not regulative elements of HBV. Virol J. 2011;8:394.PubMedPubMedCentralCrossRef
23.
go back to reference Launay O, Masurel J, Servant-Delmas A, Basse-Guerineau AL, Meritet JF, Laperche S, et al. High levels of serum hepatitis B virus DNA in patients with 'anti-HBc alone': role of HBsAg mutants. J Viral Hepat. 2011;18:721–9.PubMedCrossRef Launay O, Masurel J, Servant-Delmas A, Basse-Guerineau AL, Meritet JF, Laperche S, et al. High levels of serum hepatitis B virus DNA in patients with 'anti-HBc alone': role of HBsAg mutants. J Viral Hepat. 2011;18:721–9.PubMedCrossRef
24.
go back to reference Chaudhuri V, Tayal R, Nayak B, Acharya SK, Panda SK. Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology. 2004;127:1356–71.PubMedCrossRef Chaudhuri V, Tayal R, Nayak B, Acharya SK, Panda SK. Occult hepatitis B virus infection in chronic liver disease: full-length genome and analysis of mutant surface promoter. Gastroenterology. 2004;127:1356–71.PubMedCrossRef
25.
go back to reference Chan HL, Tsang SW, Leung NW, Tse CH, Hui Y, Tam JS, et al. Occult HBV infection in cryptogenic liver cirrhosis in an area with high prevalence of HBV infection. Am J Gastroenterol. 2002;97:1211–5.PubMedCrossRef Chan HL, Tsang SW, Leung NW, Tse CH, Hui Y, Tam JS, et al. Occult HBV infection in cryptogenic liver cirrhosis in an area with high prevalence of HBV infection. Am J Gastroenterol. 2002;97:1211–5.PubMedCrossRef
26.
go back to reference Datta S, Banerjee A, Chandra PK, Chowdhury A, Chakravarty R. Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers. J Med Virol. 2006;78:53–9.PubMedCrossRef Datta S, Banerjee A, Chandra PK, Chowdhury A, Chakravarty R. Genotype, phylogenetic analysis, and transmission pattern of occult hepatitis B virus (HBV) infection in families of asymptomatic HBsAg carriers. J Med Virol. 2006;78:53–9.PubMedCrossRef
27.
go back to reference Zhang ZH, Zhang L, Lu MJ, Yang DL, Li X. Establishment of reference sequences of hepatitis B virus genotype B and C in China. Zhonghua Gan Zang Bing Za Zhi. 2009;17:891–5.PubMed Zhang ZH, Zhang L, Lu MJ, Yang DL, Li X. Establishment of reference sequences of hepatitis B virus genotype B and C in China. Zhonghua Gan Zang Bing Za Zhi. 2009;17:891–5.PubMed
28.
go back to reference Norder H, Courouce AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004;47:289–309.PubMedCrossRef Norder H, Courouce AM, Coursaget P, Echevarria JM, Lee SD, Mushahwar IK, et al. Genetic diversity of hepatitis B virus strains derived worldwide: genotypes, subgenotypes, and HBsAg subtypes. Intervirology. 2004;47:289–309.PubMedCrossRef
29.
go back to reference Jin L, Zhang Z, Dai Y, Zhang Y, Zhang L, Li X. Molecular epidemiological study of occult hepatitis B virus infection in hemodialysis patients. Zhonghua Ganzangbing Zazhi. 2010;18:937–9.PubMed Jin L, Zhang Z, Dai Y, Zhang Y, Zhang L, Li X. Molecular epidemiological study of occult hepatitis B virus infection in hemodialysis patients. Zhonghua Ganzangbing Zazhi. 2010;18:937–9.PubMed
30.
go back to reference Rossi D, Sala L, Minisini R, Fabris C, Falleti E, Cerri M, et al. Occult hepatitis B virus infection of peripheral blood mononuclear cells among treatment-naive patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2009;50:604–11.PubMedCrossRef Rossi D, Sala L, Minisini R, Fabris C, Falleti E, Cerri M, et al. Occult hepatitis B virus infection of peripheral blood mononuclear cells among treatment-naive patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2009;50:604–11.PubMedCrossRef
31.
go back to reference Verheyen J, Neumann-Fraune M, Berg T, Kaiser R, Obermeier M. The detection of HBsAg mutants expressed in vitro using two different quantitative HBsAg assays. J Clin Virol. 2012;54:279–81.PubMedCrossRef Verheyen J, Neumann-Fraune M, Berg T, Kaiser R, Obermeier M. The detection of HBsAg mutants expressed in vitro using two different quantitative HBsAg assays. J Clin Virol. 2012;54:279–81.PubMedCrossRef
32.
go back to reference Servant-Delmas A, Mercier-Darty M, Ly TD, Wind F, Alloui C, Sureau C, et al. Variable capacity of 13 hepatitis B virus surface antigen assays for the detection of HBsAg mutants in blood samples. J Clin Virol. 2012;53:338–45.PubMedCrossRef Servant-Delmas A, Mercier-Darty M, Ly TD, Wind F, Alloui C, Sureau C, et al. Variable capacity of 13 hepatitis B virus surface antigen assays for the detection of HBsAg mutants in blood samples. J Clin Virol. 2012;53:338–45.PubMedCrossRef
33.
go back to reference La'ulu SL, Roberts WL. The analytic sensitivity and mutant detection capability of six hepatitis B surface antigen assays. Am J Clin Pathol. 2006;125:748–51.PubMedCrossRef La'ulu SL, Roberts WL. The analytic sensitivity and mutant detection capability of six hepatitis B surface antigen assays. Am J Clin Pathol. 2006;125:748–51.PubMedCrossRef
34.
go back to reference Darmawan E, Turyadi, El-Khobar KE, Nursanty NK, Thedja MD, Muljono DH. Seroepidemiology and occult hepatitis B virus infection in young adults in Banjarmasin, Indonesia. J Med Virol. 2015;87:199–207.PubMedCrossRef Darmawan E, Turyadi, El-Khobar KE, Nursanty NK, Thedja MD, Muljono DH. Seroepidemiology and occult hepatitis B virus infection in young adults in Banjarmasin, Indonesia. J Med Virol. 2015;87:199–207.PubMedCrossRef
35.
go back to reference Banerjee A, Chandra PK, Datta S, Biswas A, Bhattacharya P, Chakraborty S, et al. Frequency and significance of hepatitis B virus surface gene variant circulating among 'antiHBc only' individuals in Eastern India. J Clin Virol. 2007;40:312–7.PubMedCrossRef Banerjee A, Chandra PK, Datta S, Biswas A, Bhattacharya P, Chakraborty S, et al. Frequency and significance of hepatitis B virus surface gene variant circulating among 'antiHBc only' individuals in Eastern India. J Clin Virol. 2007;40:312–7.PubMedCrossRef
36.
go back to reference Henke-Gendo C, Amini-Bavil-Olyaee S, Challapalli D, Trautwein C, Deppe H, Schulz TF, et al. Symptomatic hepatitis B virus (HBV) reactivation despite reduced viral fitness is associated with HBV test and immune escape mutations in an HIV-coinfected patient. J Infect Dis. 2008;198:1620–4.PubMedCrossRef Henke-Gendo C, Amini-Bavil-Olyaee S, Challapalli D, Trautwein C, Deppe H, Schulz TF, et al. Symptomatic hepatitis B virus (HBV) reactivation despite reduced viral fitness is associated with HBV test and immune escape mutations in an HIV-coinfected patient. J Infect Dis. 2008;198:1620–4.PubMedCrossRef
37.
go back to reference Gunther S, Li BC, Miska S, Kruger DH, Meisel H, Will H. A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients. J Virol. 1995;69:5437–44.PubMedPubMedCentral Gunther S, Li BC, Miska S, Kruger DH, Meisel H, Will H. A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients. J Virol. 1995;69:5437–44.PubMedPubMedCentral
38.
go back to reference Zhang R, Wang L, Li J. Hepatitis B virus transfusion risk in China: proficiency testing for the detection of hepatitis B surface antigen. Transfus Med. 2010;20:322–8.PubMedCrossRef Zhang R, Wang L, Li J. Hepatitis B virus transfusion risk in China: proficiency testing for the detection of hepatitis B surface antigen. Transfus Med. 2010;20:322–8.PubMedCrossRef
39.
go back to reference Sohn YH, Oh HB, Ko SY, Lim YS, Kwon OJ. Analysis of clinical characteristics and S gene mutation of hepatitis B virus (HBV) in patients with hepatitis B surface antigen RIA negative and HBV DNA positive. Korean J Lab Med. 2009;29:224–30.PubMedCrossRef Sohn YH, Oh HB, Ko SY, Lim YS, Kwon OJ. Analysis of clinical characteristics and S gene mutation of hepatitis B virus (HBV) in patients with hepatitis B surface antigen RIA negative and HBV DNA positive. Korean J Lab Med. 2009;29:224–30.PubMedCrossRef
40.
go back to reference Zhang L, Zhang Z, Sun P, Xia G, Zhang T, Li X. Study on occult hepatitis B virus infection in family members of chronic hepatitis B virus infections patients. Zhonghua Chuanranbing Zazhi. 2010;28:159–63. Zhang L, Zhang Z, Sun P, Xia G, Zhang T, Li X. Study on occult hepatitis B virus infection in family members of chronic hepatitis B virus infections patients. Zhonghua Chuanranbing Zazhi. 2010;28:159–63.
41.
go back to reference Zhang Z, Zhang L, Dai Y, Jin L, Sun B, Su Q, et al. Occult hepatitis B virus infection among people with a family history of chronic hepatitis B virus infection. J Med Virol. 2015;87(11):1890–8.PubMedCrossRef Zhang Z, Zhang L, Dai Y, Jin L, Sun B, Su Q, et al. Occult hepatitis B virus infection among people with a family history of chronic hepatitis B virus infection. J Med Virol. 2015;87(11):1890–8.PubMedCrossRef
42.
go back to reference Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol. 2011;28:2731–9.PubMedPubMedCentralCrossRef Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol. 2011;28:2731–9.PubMedPubMedCentralCrossRef
Metadata
Title
Occult hepatitis B virus infection: influence of S protein variants
Authors
Zhenhua Zhang
Ling Zhang
Yu Dai
Yafei Zhang
Jun Li
Xu Li
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2016
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-016-0464-z

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