Evidence for an unknown agent antigenically related to the hepatitis E virus in dairy cows in the United States

Genotypes 3 and 4 hepatitis E virus (HEV) strains within the species Orthohepevirus A in the family Hepeviridae are zoonotic. Recently, a genotype 4 HEV was reportedly detected in fecal samples of cows, although independent confirmation is lacking. In this study, we first tested serum samples from 983 cows in different regions in the United States for the presence of immunoglobulin G (IgG) anti-HEV and found that 20.4% of cows were seropositive. The highest seroprevalence rate (68.4%) was from a herd in Georgia. In an attempt to genetically identify HEV in cattle, a prospective study was conducted in a known seropositive dairy herd by monitoring 10 newborn calves from birth to 6 months of age for evidence of HEV infection. At least 3 of the 10 calves seroconverted to IgG anti-HEV, and importantly the antibodies presented neutralized genotype 3 human HEV, thus, indicating the specificity of IgG anti-HEV in the cattle. However, our extensive attempts to identify HEV-related sequences in cattle using broad-spectrum reverse transcription-polymerase chain reaction assays and MiSeq deep-sequencing technology failed. The results suggest the existence of an agent antigenically related to HEV in cattle, although, contrary to published reports, we showed that the IgG recognizing HEV in cattle was not caused by HEV infection.