Detection of antibodies to HAV 3C proteinase in experimentally infected chimpanzees and in naturally infected children.

Commercial assays for the diagnosis of hepatitis A detect antibody to hepatitis A virus (anti-HAV), but they cannot discriminate between antibody resulting from infection and antibody induced by inactivated vaccine. With the licensing and increasing use of inactivated hepatitis A vaccines, there is a need for a test to distinguish between infection and vaccination. Since antibodies to viral non-structural proteins are elicited by infection but not by vaccination with inactivated vaccine, we developed and evaluated a test for such antibodies. The antibody response to the non-structural 3C proteinase (anti-3C) of virus HAV was studied by ELISA in chimpanzees experimentally infected with virulent (wild type) or with attenuated HAV strains and in children who received inactivated HAV vaccine or placebo during a vaccination trial in Nicaragua. Anti-3C was detected in 89% of 18 chimpanzees infected with wild-type HAV strains and 27% of 26 chimpanzees infected with attenuated HAV strains. There was a direct correlation between severity of hepatitis and magnitude of the anti-3C response. In the vaccine trial, anti-3C was detected only in children who were infected with HAV during the study; IgG anti-3C persisted for at least 15 months after infection in one child. Vaccinated and uninfected children remained negative for anti-3C. The anti-3C response can be regarded as an indicator of viral replication. Its detection should be useful for distinguishing between antibody acquired in response to HAV infection and antibody induced by immunization with inactivated vaccine.

Evidence that the genomic RNA of hepatitis E virus is capped.

Hepatitis E virus (HEV) is an unclassified virus with a positive-sense RNA genome and an undefined replication strategy. In order to determine whether the HEV genome is capped or not, we developed a reverse transcription-PCR assay that is based on the ability of a monoclonal antibody to recognize 7-methylguanosine (m(7)G). Antibody to m(7)G bound RNA extracted from virions of two different HEV genotypes. The cap analog competitively inhibited the binding of virion RNAs, demonstrating that HEV has a capped RNA genome.

Evidence for widespread infection of wild rats with hepatitis E virus in the United States.

Hepatitis E is an important medical pathogen in many developing countries but is rarely reported from the United States, although antibody to hepatitis E virus (anti-HEV) is found in > 1% of U.S. citizens. Zoonotic spread of the virus is suspected. Sera obtained from 239 wild rats trapped in widely separated regions of the United States were tested for anti-HEV. Seventy-seven percent of rats from Maryland, 90% from Hawaii, and 44% from Louisiana were seropositive for anti-HEV. Rats from urban as well as rural areas were seropositive and the prevalence of anti-HEV IgG increased in parallel with the estimated age of the rats, leading to speculation that they might be involved in the puzzling high prevalence of anti-HEV among some U.S. city dwellers. The discovery of a in rats in the United States and the recently reported discovery that HEV is endemic in U.S. swine raise many questions about transmission, reservoirs, and strains of HEV in developed countries.