Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis

Abstract

The appearance of mutations of hepatitis B virus (HBV) Serum hepatitis B virus (HBV) DNA from 4 infants with genome during natural infection can be attributed to the fulminant hepatitis B, 3 infants with acute self-limited hepatioccurrence of errors in its replication via the reverse trantis B, and 15 infants with chronic HBV infection were ampliscription of an RNA intermediate. 1 Various genomic variants fied by polymerase chain reaction followed by direct sequencinvolving the precore or core region of HBV have been deing of the region of HBV genome encoding the major antigenic scribed among patients with fulminant, acute self-limited, as epitopes of hepatitis B surface antigen (HBsAg). All infants well as chronic hepatitis B. 2-4 Hepatitis B surface antigen were born to carrier mothers and administered immunopro-(HBsAg)-specific antibody (anti-HBs) is believed to provide phylaxis from birth. Serum HBV DNA from 13 carrier children protective immunity and aid in clearance of HBV. Point muborn to carrier mothers who did not receive immunoprophytations in the surface (S) gene that result in amino acid laxis and had comparable length of infection were studied as substitutions in the common ''a'' antigenic determinant, controls. An S mutant (residue 126, Thr to Ala) initially found which lies between amino acids 124 and 147, can alter Bin an infant with fulminant hepatitis was replaced by another cell epitopes of HBsAg, leading to immunological escape from S mutant (residue 145, Gly to Arg) 4 days later. In a girl with the host immunity elicited by either vaccination or previous chronic hepatitis B, Ala-126 variant and Arg-145 variant were infection.5 For instance, HBV escape mutants with a glycine found at 17 and 25 months of age, respectively. The Arg-145 (Gly) to arginine (Arg) substitution at amino acid residue variant persisted for 8 years in an asymptomatic male carrier 145 with a loss in the group specific antigen determinant and for 1 year in an infant with chronic hepatitis B. The Ala-were reported to occur in vaccinated Italian infants born to 126 variant persisted for 11 years in one child who had an HBsAg-positive mothers and in liver transplant recipients early loss of hepatitis B e antigen. In the majority of the treated with monoclonal anti-HBs. 6,7 Investigators from Jainfants' mothers, corresponding mutations in HBsAg were not pan, Singapore, and Gambia have described similar vaccine detected in serum by direct sequencing. The S mutants de-escape mutants with nucleotide change resulting in amino tected in three carrier infants were not found in their mothers' acid substitution elsewhere in the ''a'' determinant. [8][9][10] The serum after cloning and sequencing of 10 DNA clones from overall frequency of these mutations is unknown, and their each maternal sample. None of the 13 control patients had biological significance remains speculative. detectable S mutants. These results suggest that S variantsIn Taiwan, a mass immunization program against hepatitis emerge or are selected under the immune pres...

Clinical relevance of hepatitis B viral mutations

“…Taiwanese studies have evaluated infants with surface gene mutant HBV isolates with associated fulminant hepatitis B (n ϭ 4), acute hepatitis B (n ϭ 3), and chronic hepatitis B (n ϭ 15) despite vaccination and immunoprophylaxis. 42 The HBV surface protein variants noted in this study were clustered within the a determinant and included aa-145 gly to arg, aa-126 thr to ala, and aa-129 gln to arg. However, when HBV isolates from the mothers of these affected infants were sequenced, only 1 of 22 were found to express an HBV surface mutant (aa-129 gln to arg).…”

Serological and molecular epidemiological outcomes after two decades of universal infant hepatitis B virus (HBV) vaccination in Nunavut, Canada

“…As mentioned previously, the 'a' determinant is a highly conserved region of HBsAg, and contains the majority of epitopes that host anti-HBs antibodies will target. Mutations within the 'a' determinant have been observed in persons who have received the HBV vaccine in several regions of the world [4,[94][95][96]. The selective pressure may increase the emergence of surface mutants compared to wild-type.…”

Characterization of a Hepatitis B virus strain in southwestern Paraná, Brazil, presenting mutations previously associated with anti-HBs Resistance

“…Point mutations in the S gene that result in amino acid substitutions in the common "a" antigenic determinant, which lies between amino acids 124 and 147, can alter B-cell epitopes of HBsAg, leading 26 to variants that escape from the host immune response elicited by vaccination or previous infection 16 . WALLACE & CARMAN (1997) suggested increasing the area of investigation in the "S" region to include the entire major hydrophilic region (MHR) which comprises amino acids 99 to 169.…”