Interferon alone or combined with ribavirin for acute prolonged infection with hepatitis C virus in chimpanzees.

Infection with hepatitis C virus (HCV) persisted for longer than 29 weeks in 2 chimpanzees after they had been inoculated with it experimentally. One of them (C-210) received short-term subcutaneous interferon-α (IFN-α) 6 million units (MU) daily for 7 days at week 29. He cleared HCV RNA from the serum and remained negative for it during 25 weeks after the withdrawal of IFN.

Minimum infectious dose of hepatitis B virus in chimpanzees and difference in the dynamics of viremia between genotype A and genotype C.

Background: In planning optimal hepatitis B virus (HBV) blood screening strategies, the minimum infectious dose and early dynamics of HBV need to be determined for defining the window period for HBV DNA as well as for hepatitis B surface antigen (HBsAg).

Study Design And Methods: Pairs of chimpanzees were inoculated with preacute-phase inocula containing HBV of genotype A or genotype C to determine the minimum infectious dose, and two pairs of chimps infected with the lowest infectious dose of genotypes A and C were followed for HBV markers.

Results: The minimum 50 percent chimpanzee infectious dose (CID50) was estimated to be approximately 10 copies for genotype A and for genotype C.

Early dynamics of hepatitis C virus in the circulation of chimpanzees with experimental infection.

Two chimpanzees were inoculated with hepatitis C virus (HCV) and followed on a daily basis for 12 days. HCV RNA became detectable in their sera on day 5 by polymerase chain reaction with the detection limit of 10(2) copies/ml. Based on an exponential growth observed until 8 or 9 days after inoculation in their sera, the doubling time of HCV in the circulation was estimated at 6.

Titration of hepatitis C virus in chimpanzees for determining the copy number required for transmission.

Objective: To determine the copy number of hepatitis C virus (HCV) RNA, determined by nucleic acid amplification test (NAT) for screening blood units in Japan, that can transmit infection to chimpanzees.

Methods: Fresh-frozen plasma with markers of HCV infection, as well as inocula pedigreed from 1 of them, were evaluated for the infectious activity in chimpanzees.

Results: One unit each (273-282 ml) of fresh-frozen plasma from 2 blood donors or a pool from 13 donors to make a unit, which contained high-titered antibody to HCV but without HCV RNA detectable by NAT, did not infect any of 3 chimpanzees.

In vivo and in vitro evidence that cross-reactive antibodies to C-terminus of hypervariable region 1 do not neutralize heterologous hepatitis C virus.

The hypervariable region 1 (HVR1) of hepatitis C virus (HCV) may contain neutralizing epitopes. A chimpanzee in whom cross-reactive anti-HVR1 antibodies had been induced by immunization was challenged with heterologous HCV for clarifying whether cross-reactive anti-HVR1 antibodies can neutralize heterologous HCV. Acute hepatitis C occurred in this chimpanzee after the challenge.