Abstract. 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 Ͼ 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 anti-HEV 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.Hepatitis E is the first or second most important cause of acute clinical hepatitis in many developing countries of Asia, the Middle East and North Africa. Hepatitis E can occur sporadically or in epidemics and the peak clinical attack rate usually occurs in young adults. 1 Hepatitis E is caused by hepatitis E virus (HEV), an unclassified virus that is enterically transmitted. Antibody to HEV (anti-HEV), indicative of past infection, has been detected in only 5-60% of the general population of developing countries where the disease is endemic. 2 The peak age-specific acquisition of anti-HEV occurs in young adults. 3 The relatively low prevalence of antibody in young children and the relatively late acquisition of infection in some populations are unusual patterns for a virus that is believed to be transmitted principally by the fecal-oral route. Although this pattern is consistent with a cohort effect, studies from India suggest that this is not the explanation. 3 In industrialized countries, clinical hepatitis E is rarely reported and the few cases that do occur are generally among individuals who acquired their infection in a developing country. 4,5 It is therefore perplexing that anti-HEV has been detected in these industrialized countries in 0.4-5% of healthy populations (generally blood donors), even in the absence of known risk factors. 6 In some studies, even higher prevalences of anti-HEV have been found in specific populations in the United States. 7,8 Although the specificity of some tests used for measuring anti-HEV has been questioned, it is unlikely that false-positive results can explain the relatively high prevalence of anti-HEV in populations with no significant clinical hepatitis E.It has been proposed that animal reservoirs of HEV exist in some regions and that human infections may represent, in part, a zoonosis. The successful transmission of HEV to swine, rats, and sheep in the former USSR and in Asia has been reported, as has the transmission of HEV to several non-human primate species. 9-14 Antibody to HEV has been detect...

The role of rats in human hepatitis E virus (HEV) infections remains controversial. A genetically distinct HEV was recently isolated from rats in Germany, and its genome was sequenced. We have isolated a genetically similar HEV from urban rats in Los Angeles, California, USA, and characterized its ability to infect laboratory rats and nonhuman primates. Two strains of HEV were isolated from serum samples of 134 wild rats that had a seroprevalence of antibodies against HEV of ≈80%. Virus was transmissible to seronegative Sprague-Dawley rats, but transmission was spotty and magnitude and duration of infection were not robust. Viremia was higher in nude rats. Serologic analysis and reverse transcription PCR were comparably sensitive in detecting infection. The sequence of the Los Angeles virus was virtually identical to that of isolates from Germany. Rat HEV was not transmissible to rhesus monkeys, suggesting that it is not a source of human infection.H epatitis E virus (HEV) is a major cause of epidemic waterborne and sporadic hepatitis in developing countries. Hepatitis E is caused principally by HEV genotypes 1 and 2 (1). Recently, hepatitis E has been diagnosed with increasing frequency as a cause of sporadic hepatitis in industrialized countries (2). Additionally, a large proportion (<20%) of populations of such countries have antibodies against HEV in the absence of any recognized hepatitis (3-5), and evidence is increasing that these antibodies might be the result of subclinical infections acquired zoonotically.Strains of HEV representing genotypes 3 and 4, which have been isolated from humans with hepatitis E, regularly infect pigs worldwide (6), and infection in humans caused by eating undercooked meat from domestic pigs, wild boar, and several species of wild deer has been documented (6,7). However, many, if not most, persons who have unexplained antibodies against HEV do not eat undercooked pork or venison, raising the possibility that other animals or modes of zoonotic transmission exist. It is noteworthy that swine handlers in the United States have a higher incidence of antibodies against HEV than do healthy blood donors, even though pork is generally thoroughly cooked in the United States. Therefore, eating pork is unlikely to explain the prevalence of antibodies against HEV in this country.Numerous species, including rodents, have been found to have antibodies reactive with capsid protein of human HEV strains, and HEV closely related to genotypes 3 or 4 has been recently isolated from rabbits (8), cattle (9), and sheep (10). However, an HEV strain recently isolated from rats was unique and only distantly related to known strains (11). Thus, it is important to understand how this rat virus is related to human infections. Rats are particularly interesting as a potential source of human infections because although they are not a human food, they have a high seroprevalence of antibodies against HEV (12,13) and they are ubiquitous and in close contact with humans everywhere.We have demonstrated that a hi...

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 (m7G). Antibody to m7G 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.