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  • Title: Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero?
    Author: Milich DR, Jones JE, Hughes JL, Price J, Raney AK, McLachlan A.
    Journal: Proc Natl Acad Sci U S A; 1990 Sep; 87(17):6599-603. PubMed ID: 2395863.
    Abstract:
    Infants born to hepatitis B virus carrier mothers, who express a secreted form of the nucleocapsid antigen designated HBeAg, invariably become persistently infected. To investigate the role of immunologic tolerance mechanisms in chronic infection of the newborn, we have generated HBeAg-expressing transgenic mice. HBeAg-expressing transgenic mice were tolerant to both HBeAg and the nonsecreted nucleocapsid (hepatitis B cor antigen/HBcAg) at the T-cell level. Transgenic mice did not produce antibody to HBeAg but did produce anti-HBc antibody in vivo and in vitro. The coexistence of tolerance to HBc/HBe T-cell determinants and anti-HBc antibody production in vivo parallels the immunologic status of neonates born to carrier mothers. It was also demonstrated that the maintenance of T-cell tolerance to HBcAg/HBeAg required the continued presence of the tolerogen and in its absence persisted for less than 16 weeks. The reversibility of T-cell tolerance to HBcAg/HBeAg may explain the inverse correlation between age of infection and rates of viral persistence. These observations suggest that a function of the HBeAg may be to induce immunologic tolerance in utero. Expression of HBeAg may represent a viral strategy to guarantee persistence after perinatal infection.
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