Hepatitis B Virus Infection in Chimpanzees: Titration of Subtypes

Abstract

Thirty-four chimpanzees were inoculated with sera containing the adw, ayw, adr, or ayr subtype of hepatitis B surface antigen (HBs Ag). Twenty-nine of the animals became infected with hepatitis B virus, and in every instance the subtype of HBs Ag in the infected animal was the same as the subtype in the inoculum. Infectivity titers were established for the adw and ayw inocula. The patterns of serologic events varied in the infected animals but included most of the typical patterns of serologic change seen in human cases of type B hepatitis. Mild disease, manifested by elevated concentrations of serum enzymes and changes detected by liver biopsy, occurred in 23 of the 29 infected animals.

Effects of age and viral determinants on chronicity as an outcome of experimental woodchuck hepatitis virus infection

“…Although the measurable infectious titers of WHV were as high or higher than those of some HBV 3,23 and duck HBV (DHBV) 24 inocula, results for IV titrations of HBV in chimps 23 and of DHBV in ducks 24 indicate that 1 infectious dose 50% of virus corresponded to between 1 and 10 GEq. In 1 IV titration experiment in adult woodchucks, the relative infectivity of WHV8P0 was P/I ϭ 179.…”

“…The infectious dose of virus has been shown to affect the incubation period in the adult chimpanzee model of HBV infection, 3 but the effects on chronicity as an outcome of infection cannot be readily assessed in this species. The infectious dose of DHBV influences incubation time in the duck model and also influences the early time window within which young ducklings are susceptible to chronicity as an outcome of infection.…”

“…1,2 Development of the model has evolved to use woodchucks bred and reared under controlled environmental conditions, virus-and hostspecific assays for viral infection and disease, and standardized WHV inocula. Because titered HBV inocula have proven invaluable for developing the chimpanzee as a predictive model of HBV infection, disease, and vaccine protection, 3 titered WHV inocula were considered essential for further defining host and viral determinants that promote chronicity and disease progression to hepatocellular carcinoma (HCC) in hepadnavirus infection. In this study, we measured the infectivity of several WHV inocula and, using controlled doses of virus, showed that both animal age and viral determinants can affect chronicity as an outcome of WHV infection.…”

Identification of hepatitis B virus indigenous to chimpanzees

“…HBV is the prototype of the Hepadnaviridae family, which includes mammalian viruses (genus Orthohepadnavirus), such as human HBV, woodchuck hepatitis virus (1), Beechey ground squirrel hepatitis virus (2), and Arctic ground squirrel hepatitis virus (3) and avian viruses (genus Avihepadnavirus) (4,5). Soon after characterization of human HBV, chimpanzees were shown to be susceptible to experimental HBV infection (6). In addition, testing of wild-caught chimpanzees revealed that 3-6% were positive for hepatitis B surface antigen (HBsAg) (7)(8)(9)(10), a marker of chronic HBV infection, and as many as 50% of older animals were positive for antibody to HBsAg (anti-HBs), a marker of resolved infection (11).…”

The use of non-human primates as animal models for the study of hepatitis viruses

“…The immunobiology of HBV infection in chimpanzees is similar to that observed in humans, except that the disease is generally less severe (79,80). After the incubation period of 4-10 weeks, the disease can be monitored by the elevation in liver enzymes, histopathological changes in liver tissue and the evolution of HBV markers (HBsAg, antiHBc, anti-HBs and HBV-DNA).…”