Selection of hepatitis B surface “escape” mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function

Shields, PL; Owsianka, Ania M.; Carman, William F.; Boxall, Elizabeth; Hübscher, Stefan G.; Shaw, J; O'Donnell, Katharina; Elias, E.; Mutimer, David

doi:10.1136/gut.45.2.306

Cited by 42 publications

(25 citation statements)

References 12 publications

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“…Most isolates contained the same glycine to arginine shift as observed in the above mentioned vaccination escape mutants. This observation also confirms the finding that changes in the a epitope of the S protein allows the virus to evade antibody-mediated selective pressure [91][92][93][94][95][96][97]. The average overall reinfection rate under HBIG monotherapy ranges from 20 to 35%.…”

Section: Hbig Resistance Mutantssupporting

confidence: 73%

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Hepatitis B: Where Are We Today?

Eckert¹,

Struff

2006

Transfus Med Hemother

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Hepatitis B still is a major challenge of modern medicine. Here, we summarize the disease, the life cycle of the virus, the emergence of drug-resistant mutant strains and resulting consequences for new drug development. Hepatitis B has a worldwide prevalence of 0.1-20%. It occurs in an acute and a chronic phase. The acute phase is characterized by viral replication, onset of immune response leading to destruction of infected hepatocytes and, in most cases, viral clearance and lifelong immunity. Clinical symptoms are observed in this phase. The chronic phase is characterized by lifelong persistence of the virus, often without clinical symptoms but bearing the risk of hepatic cirrhosis or hepatocellular carcinoma. Both phases are distinguished by detection of viral antigens and hepatitis B antibodies in the blood. The hepatitis B virus (HBV) shows several features unique for hepadnaviridae: i) formation of covalently closed-circle DNA (cccDNA) as template for viral DNA replication and synthesis of viral RNAs and ii) a reverse transcription step in the synthesis of new viral DNAs. These features are the prime targets in antiviral drug development. Unfortunately, with the exception of interferon, resistant mutant strains of HBV were found after widespread use of every new drug so far. Therefore, combination therapies aimed at different targets are being discussed so that the selective pressure can no longer be compensated by HBV. This paper is the first part of a trilogy concerning HBV which will also discuss the situation regarding transplantation (second part) and blood transfusion (third part).

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Section: Hbig Resistance Mutantssupporting

confidence: 73%

“…In addition, such mutations in the S gene may also affect the polymerase protein and its function because of the overlapping reading frames for the surface and the polymerase protein (see below) [91].…”

Section: Vaccination Escape Mutantsmentioning

confidence: 99%

Hepatitis B: Where Are We Today?

Eckert¹,

Struff

2006

Transfus Med Hemother

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“…However, breakthrough infection despite induction of neutralizing antibodies has been documented and is often attributed to single amino acid substitutions within the "a" determinant (3)(4)(5)(6)(7)(8). Such immune escape mutants are also responsible for reinfection of grafted liver despite passive prophylaxis with hepatitis B immunoglobulin (HBIG) (9)(10)(11)(12)(13)(14). The mutations render the S protein poorly recognizable by antibodies raised against the wild-type (WT) virus, which forms the structural basis for both immune escape and false-negative diagnostic test results.…”

mentioning

confidence: 99%

Impaired Virion Secretion by Hepatitis B Virus Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second-Site Mutation

Kwei

Tang

Lok

et al. 2013

J Virol

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“…In accord with this notion, many researchers have demonstrated that the binding to anti-HBs antibodies is annulled by aa insertions and deletions in this region [35,36]. Consequently, HBsAg mutations may occur in aa substitutions, insertions, and/ or deletions.…”

Section: Hbsag Mutantsmentioning

confidence: 89%

Hepatitis B Virus (HBV) and S-Escape Mutants: From the Beginning until Now

Maria¹

2015

JHVRV

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Despite of the progress made in vaccine and antiviral therapy development, hepatitis B virus (HBV) infection remains a major health care problem. More than 240 million people are chronically infected worldwide showing differences in the severity of liver disease, clinical outcome and response to immune-and antiviraltherapy. Parameters associated with the host immune system (HBV specific Tand/or B-cell repertoires, defective antigen presentation and diminished Th1/ Th2 response ratio) and viral factors such as the HBV genotypes and their evolving variants/mutants, have largely contributed to explaining such differences. The unique genomic structure and replication cycle of HBV provide much opportunity for mutations to occur in any of its genes undergoing selection pressures, such as those associated with the host immune system, the hepatitis B vaccine and/ or hepatitis B immune globulin and the antiviral therapy with nucleos(t)ide analogues. Firstly, this review describes the current prevalence of S-escape mutants worldwide. Secondly, the clinical implications of such surface gene variants and the impact of universal hepatitis B vaccination on HBV mutations and genotypes are discussed. Finally, the fact that the immune escape process also extends well beyond HBV is addressed.

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Selection of hepatitis B surface “escape” mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function

Abstract: (Gut 1999;45:306-309)

Cited by 42 publications

References 12 publications

Hepatitis B: Where Are We Today?

Hepatitis B: Where Are We Today?

Impaired Virion Secretion by Hepatitis B Virus Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second-Site Mutation

Hepatitis B Virus (HBV) and S-Escape Mutants: From the Beginning until Now

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