Molecular epidemiology of hepatitis B virus mutants

Zuckerman, Arie J.; Zuckerman, Jane N.

doi:10.1002/(sici)1096-9071(199907)58:3<193::aid-jmv1>3.0.co;2-x

Cited by 56 publications

(30 citation statements)

References 9 publications

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“…Some immune escape variants were identified in the dominant population, which indicates that these variants are relatively stable in the absence of the wild-type strain. Previous reports have shown that the G145R variant is stable over time (67,68). However, infection with the dominant population of immune escape variants increases the risk of horizontal transmission in the general Indonesian population, even in vaccinated individuals.…”

Section: Discussionmentioning

confidence: 96%

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

et al. 2015

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h Quasispecies of hepatitis B virus (HBV) with variations in the major hydrophilic region (MHR) of the HBV surface antigen (HBsAg) can evolve during infection, allowing HBV to evade neutralizing antibodies. These escape variants may contribute to chronic infections. In this study, we looked for MHR variants in HBV quasispecies using ultradeep sequencing and evaluated the relationship between these variants and clinical manifestations in infected patients. We enrolled 30 Indonesian patients with hepatitis B infection (11 with chronic hepatitis and 19 with advanced liver disease). The most common subgenotype/subtype of HBV was B3/adw (97%). The HBsAg titer was lower in patients with advanced liver disease than that in patients with chronic hepatitis. The MHR variants were grouped based on the percentage of the viral population affected: major, >20% of the total population; intermediate, 5% to <20%; and minor, 1% to <5%. The rates of MHR variation that were present in the major and intermediate viral population were significantly greater in patients with advanced liver disease than those in chronic patients. The most frequent MHR variants related to immune evasion in the major and intermediate populations were P120Q/T, T123A, P127T, Q129H/R, M133L/T, and G145R. The major population of MHR variants causing impaired of HBsAg secretion (e.g., G119R, Q129R, T140I, and G145R) was detected only in advanced liver disease patients. This is the first study to use ultradeep sequencing for the detection of MHR variants of HBV quasispecies in Indonesian patients. We found that a greater number of MHR variations was related to disease severity and reduced likelihood of HBsAg titer.T he high mutation rate of hepatitis B virus (HBV), which is attributable to the lack of a proofreading function in its polymerase and the high replication rate of the virus, induces viral diversity, referred to as viral quasispecies. Many studies have demonstrated that the identification of HBV quasispecies may help predict disease progression and therapeutic outcomes (1-3). Accordingly, HBV variants in the quasispecies pool are probably clinically relevant (4).The surface (S) region used to classify HBV strains is responsible for the expression of hepatitis B surface antigen (HBsAg). HBsAg is the major target for viral neutralization by the immune responses of the host, either naturally or by vaccine-induced antibodies. However, the major hydrophilic region (MHR) located in the central HBsAg, comprising amino acids 100 to 169, contains many discontinuous B-cell epitopes that are recognized by hepatitis B surface antibodies (anti-HBs) (5-7). The exact border of the neutralizing domain of the MHR region is still unclear, although the ␣-determinant region (amino acids 124 to 147) within the MHR has been known to be strongly involved in antibody binding (8,9). Moreover, many studies have noted that variations within the MHR can alter the antigenicity of HBsAg and are responsible for (i) the evasion of vaccine-induced antibodies, (ii) the failure of immu...

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Section: Discussionmentioning

confidence: 96%

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

et al. 2015

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“…These have mutations at amino acid 124 to 147 of HBsAg and may not be detected by current HBsAg test assays (10). The existing HBV vaccines also may not protect vaccinees from infections by these mutants (11). Immune pressure from vaccination against HBV may induce the occurrence or selection of HBsAg mutations (12).…”

Section: Public Health Surveillance Of Hbv In Canadamentioning

confidence: 99%

“…Other prevention strategies: The current risk of HBV transmission through blood transfusion or organ transplantation is minimal due to blood or organ donor screening and HBsAg testing. However, residual risk still exists due to a window period (49) and HBsAg-mutant infections (11).…”

Section: Prevention Of Nosocomial Transmission Of Hbvmentioning

confidence: 99%

Epidemiology of Hepatitis B in Canada

Zhang¹,

Zou²,

Giulivi³

2001

Canadian Journal of Infectious Diseases and Medical Microbiolog

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OBJECTIVE: To provide a current and comprehensive review of the epidemiology of hepatitis B virus (HBV) in Canada. DATA SOURCES: Published and unpublished epidemiological studies and surveillance reports of the past decade, primarily from Canada were studied. Fifty reports addressing HBV surveillance, incidence and prevalence, transmission-associated risk factors, co-infections, and prevention strategies were reviewed. DATA SYNTHESIS: HBV infection is an important vaccine-preventable infectious disease in Canada. The incidence rate of clinically recognized, acute HBV infection in 1998/1999 was estimated to be 2.3/100,000 people or approximately 700 cases a year. The prevalence of HBV carriers is estimated to be 0.5% to 1.0% of the population, but varies substantially according to population-specific risk factors. Most acute HBV infections are associated with injection drug use or high risk heterosexual activities, but 20% to 30% of acute cases did not report any identified risk factors. Surveillance activities such as the National Notifiable Disease Reporting system provide information regarding trends and risk factors. The primary preventive strategy for HBV consists of universal immunization for preadolescents and/or infants. Other strategies, such as the universal prenatal screening and postnatal immunization, and the prevention of nosocomial acquistion, are also important. The recently described hepatitis B surface antigen (HBsAg) escape mutants may not be detected by current HBsAg test assays, and the existing HBV vaccines may not protect vaccinees from infections by such mutants. CONCLUSION: Ongoing surveillance and research are required to assess risk factors for HBV transmission, evaluate the effectiveness of immunization programs and monitor the impact of HBsAg escape mutants. SOURCES DES DONNÉES :Études épidémiologiques publiées et non publiées et rapports épidémiologiques des dix dernières années principalement au Canada. Cinquante rapports sur l'épidémiologie du HBV, son incidence et sa prévalence, les facteurs de risque de sa transmission, les co-infections et les stratégies de prévention ont été passés en revue. SYNTHÈSE DES DONNÉES : L'infection au HBV est une importante maladie infectieuse qu'il est possible de prévenir au moyen d'un vaccin. Au Canada, l'incidence de l'infection aiguë au HBV cliniquement reconnue en 1998-1999 a été estimé à 2,3/100 000 personnes ou à approximativement 700 cas par année. La prévalence des porteurs du HBV se situerait à 0,5 -1 % dans la population, avec une variation substantielle selon les facteurs de risque. La plupart des infections au HBV aiguës sont associées à l'utilisation de drogues par injection ou à des activités hétérosexuelles à haut risque, mais dans 20 à 30 % des cas aigus aucun facteur de risque n'a clairement pu être identifié. Les mesures épidémiologiques comme le système de maladies à déclaration obligatoire offrent des renseignements sur les tendances ou les facteurs de risque. La principale stratégie préventive contre le HBV est l'immunisation ...

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“…Such mutants have also been reported in association with escape from vaccineinduced immunity [Oon et al, 1995;Carman, 1997;Ho et al, 1998;Chong-Jin et al, 1999;He et al, 2001;Lee et al, 2001;Seddigh-Tonekaboni et al, 2001] and with failures of therapy with specific immunoglobulin in newborns from carrier women and in liver-transplant recipients [Harrison et al, 1994;Oon et al, 1996Oon et al, , 2002Brind et al, 1997;Carman, 1997;Ngui et al, 1997;Protzer-Knolle et al, 1998;Santantonio et al, 1999;Roznovsky et al, 2000;Liu et al, 2002]. The amino-acid substitution Gly145Arg has been reported most frequently [Francois et al, 2001], and is known to be stable [Zuckerman and Zuckerman, 1999].…”

Section: Introductionmentioning

confidence: 99%

Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers

Avellón

Echevarría

2005

Journal of Medical Virology

101

125

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The prevalence in the population of hepatitis B virus (HBV) surface antigen (HBsAg) variants that may impair diagnosis, or allow the virus to escape vaccine‐induced immunity or passive immunoglobulin therapy is unknown. A genome fragment encoding HBsAg amino acids 112–212 was amplified and sequenced from the sera of 272 unselected DNA‐positive, HBV‐chronic carriers from Spain. The genotype and the HBsAg subtype were predicted from the sequences. Analysis of amino‐acid positions 112–157 revealed single or multiple substitutions in 39% of the carriers studied. Mutations were not detected for residues 121, 135, 137, 139, 140, 141, 142, 146, 147, 148, 149, 151, 152, 153, 155, 156, and 157. Substitutions reported previously to be in association with failures of diagnostic tests or with vaccine or immunoglobulin therapy escape were found in 12.5%, 6.6%, and 9.2% of carriers, respectively. Met133Thr (2.2%); Gln129His, Met133Ile, Phe/Tyr134Asn (1.8%); Phe/Tyr134Leu, Gly145Ala (1.5%), and Pro120Thr (1.1%) were the most frequent. Other substitutions, including Gly145Arg (0.4%), were found at a frequency of less than 1%. Samples containing HBV mutants were tested with three commercial assays for HBsAg screening. Almost all the mutants reacted to the upper cut‐off values of the assays, but six samples with weak reactivity with one or more of the methods were also found. Thus, HBV mutants with a potential impact on clinical and public health issues are moderately frequent among chronic carriers from Spain, although their influence on the performance of diagnostic tests seems to be slight. J. Med. Virol. 78:24–36, 2006. © 2005 Wiley‐Liss, inc.

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Molecular epidemiology of hepatitis B virus mutants

Cited by 56 publications

References 9 publications

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

Ultradeep Sequencing for Detection of Quasispecies Variants in the Major Hydrophilic Region of Hepatitis B Virus in Indonesian Patients

Epidemiology of Hepatitis B in Canada

Frequency of hepatitis B virus ‘a’ determinant variants in unselected Spanish chronic carriers

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