SURFACE GENE MUTANTS OF HEPATITIS-B VIRUS IN INFANTS WHO DEVELOP ACUTE OR CHRONIC INFECTIONS DESPITE IMMUNOPROPHYLAXIS

Serum hepatitis B virus (HBV) DNA from 4 infants with fulminant hepati tis B, 3 infants with acute self-limited hepatitis B, and 15 infants w ith chronic HBV infection were amplified by polymerase chain reaction followed by direct sequencing of the region of HBV genome encoding the major antigenic epitopes of hepatitis B surface antigen (HBsAg), All infants were born to carrier mothers and administered immunoprophylaxi s from birth, Serum HBV DNA from 13 carrier children born to carrier m others who did not receive immunoprophylaxis and had comparable length of infection were studied as controls. An S mutant (residue 126, Thr to Ala) initially found in an infant with fulminant hepatitis was repl aced by another S mutant (residue 145, Gly to Arg) 4 days later, In a girl with chronic hepatitis B, Ala-126 variant and Arg-145 variant wer e found at 17 and 25 months of age, respectively, The Arg-145 variant persisted for 8 years in an asymptomatic male carrier and for 1 year i n an infant with chronic hepatitis B. The Ala-126 variant persisted fo r 11 years in one child who had an early loss of hepatitis B e antigen . In the majority of the infants' mothers, corresponding mutations in HBsAg were not detected in serum by direct sequencing, The S mutants d etected in three carrier infants were not found in their mothers' seru m after cloning and sequencing of 10 DNA clones from each maternal sam ple. None of the 13 control patients had detectable S mutants. These r esults suggest that S variants emerge or are selected under the immune pressure generated by the host or by administration of hepatitis B im mune globulin and hepatitis B vaccination. An S mutant (residue 129, G ln to Arg) found in one mother-infant pair suggested a direct maternal -infant transmission, resulting in immunoprophylaxis failure. None of the family members of children infected with Arg-145 variant had the s ame variant infection, implying this variant's low transmissability.