Restricted Enzooticity of Hepatitis E Virus Genotypes 1 to 4 in the United States

Abstract

Hepatitis E is recognized as a zoonosis, and swine are known reservoirs, but how broadly enzootic its causative agent, hepatitis E virus (HEV), is remains controversial. To determine the prevalence of HEV infection in animals, a serological assay with capability to detect anti-HEV-antibody across a wide variety of animal species was devised. Recombinant antigens comprising truncated capsid proteins generated from HEV-subgenomic constructs that represent all four viral genotypes were used to capture anti-HEV in the test sample and as an analyte reporter. To facilitate development and validation of the assay, serum samples were assembled from blood donors (n ‫؍‬ 372), acute hepatitis E patients (n ‫؍‬ 94), five laboratory animals (rhesus monkey, pig, New Zealand rabbit, Wistar rat, and BALB/c mouse) immunized with HEV antigens, and four pigs experimentally infected with HEV. The assay was then applied to 4,936 sera collected from 35 genera of animals that were wild, feral, domesticated, or otherwise held captive in the United States. Test positivity was determined in 457 samples (9.3%). These originated from: bison (3/65, 4.6%), cattle (174/1,156, 15%), dogs (2/212, 0.9%), Norway rats (2/318, 0.6%), farmed swine (267/648, 41.2%), and feral swine (9/306, 2.9%). Only the porcine samples yielded the highest reactivities. HEV RNA was amplified from one farmed pig and two feral pigs and characterized by nucleotide sequencing to belong to genotype 3. HEV infected farmed swine primarily, and the role of other animals as reservoirs of its zoonotic spread appears to be limited.Hepatitis E virus (HEV), the causative agent of hepatitis E, is a nonenveloped, single-stranded, positive-sense RNA virus that belongs to the Hepeviridae family (11). Among the mammalian HEV, at least four genotypes have been recognized (47). In addition, two putative genotypes of HEV, one genotype from the Norway rat (Rattus norvegicus) (25) and the other from a wild boar (56), were recently reported. In addition to mammalian HEV strains, avian HEV (38) and the newly described cutthroat trout virus represent new genera (3). Among mammalian HEV, genotypes 1 and 2 are primarily associated with fecal-oral transmission among humans which in developing countries can lead to waterborne epidemics of jaundice. Genotypes 3 and 4 circulate in humans and several animal species, and are associated with sporadic infection among humans in industrialized countries (57). Hepatitis E is mostly self-limiting but can progress to fulminant liver failure especially in pregnant women, and chronic HEV infection resulting in cirrhosis has been observed among solid-organ-transplant recipients and other immunosuppressed people (32).HEV infection and hepatitis E in industrialized countries, including the United States, are more common than previously recognized (33,58). A study conducted in a large civilian, noninstitutionalized U.S. population found an average anti-HEV-IgG seroprevalence rate of 21%, with a strongly positive

Seroprevalence of hepatitis E virus in Lithuanian domestic pigs and wildlife

“…We noticed seroprevalence of 11.76% in moose and no positive samples of 3 European bison. Meanwhile, in the United States where bison meat is increasingly consumed, 4.6% of domesticated bison (Bison bison) were positive for HEV antibodies (Dong et al 2011). Notably, the absence of seropositivity in European bison samples is not significant due to the small sample size, but the results are in line with a report from Poland where HEV antibodies were not found in any of the 68 European bison (Bison bonasus) tested (Larska et al 2015).…”

Host Immune Status and Response to Hepatitis E Virus Infection

“…2). HEV-3 is prevalent among swine worldwide (71)(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86) as well as in other mammals, including deer and mongooses (83,(87)(88)(89), though little is known about the sylvatic circulation of HEV.…”

“…It has been recognized recently that patients who have had solid-organ or bone marrow transplants are at risk of developing chronic HEV infection if they are infected after their transplant while being treated with immunosuppressive drugs to prevent rejection of the allograft (76,(254)(255)(256)(257). Kamar and colleagues evaluated the factors associated with chronic hepatitis in 85 patients with HEV infection from 17 transplant centers in Europe and North America (275) (Fig.…”

Serological evidence of Hepatitis E Virus infection in Antioquia, Colombia slaughtered pigs

“…In the United States seropositivity reached 41% (12), 90% in New Zealand (13), 100% in Mexico (14) and 98% in Spain (15). Studies in Latin America have reported the circulation of HEV in pigs in Argentina (16), Brazil (17), Chile (18), Costa Rica (19) and Mexico (14).…”