Genetic and Experimental Evidence for Cross-Species Infection by Swine Hepatitis E Virus

ABSTRACT Prior to the recent discovery of the swine hepatitis E virus (swine HEV) in pigs from the midwestern United States, HEV was not considered endemic to this country. Since swine HEV is antigenically and genetically related to human strains of HEV, it was important to characterize this new virus further. The infectivity titer of a pool of swine HEV in pigs was determined in order to prepare a standardized reagent and to evaluate the dose response in pigs. Although the sequence of swine HEV varied extensively from those of most human strains of HEV, it was very closely related to the two strains of human HEV (US-1 and US-2) isolated in the United States. The U.S. strains which were recently recovered from two patients with clinical hepatitis E in the United States shared ≥97% amino acid identity with swine HEV in open reading frames 1 and 2. Phylogenetic analyses of different regions of the genome revealed that swine HEV and the U.S. strains grouped together and formed a distinct branch. These results suggested that swine HEV may infect humans. When we inoculated rhesus monkeys and a chimpanzee, experimental surrogates of humans, with swine HEV, the primates became infected. Furthermore, in a reciprocal experiment, specific-pathogen-free pigs were experimentally infected with the US-2 strain of human HEV that is genetically similar to swine HEV. These results provided experimental evidence for cross-species infection by the swine virus. Thus, humans appear to be at risk of infection with swine HEV or closely related viruses.

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Detection by Reverse Transcription-PCR and Genetic Characterization of Field Isolates of Swine Hepatitis E Virus from Pigs in Different Geographic Regions of the United States

Journal of Clinical Microbiology ◽

10.1128/jcm.40.4.1326-1332.2002 ◽

2002 ◽

Vol 40 (4) ◽

pp. 1326-1332 ◽

Cited By ~ 235

Author(s):

F. F. Huang ◽

G. Haqshenas ◽

D. K. Guenette ◽

P. G. Halbur ◽

S. K. Schommer ◽

...

Keyword(s):

United States ◽

Reverse Transcription ◽

Hepatitis E Virus ◽

Genetic Characterization ◽

Hepatitis E ◽

The United States ◽

Reverse Transcription Pcr ◽

Swine Hepatitis ◽

Geographic Regions

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Identity of a Novel Swine Hepatitis E Virus in Taiwan Forming a Monophyletic Group with Taiwan Isolates of Human Hepatitis E Virus

Journal of Clinical Microbiology ◽

10.1128/jcm.37.12.3828-3834.1999 ◽

1999 ◽

Vol 37 (12) ◽

pp. 3828-3834 ◽

Cited By ~ 163

Author(s):

Sen-Yung Hsieh ◽

Xiang-Jin Meng ◽

Ying-Hua Wu ◽

Shih-Tung Liu ◽

Albert W. Tam ◽

...

Keyword(s):

Hepatitis E Virus ◽

Genomic Sequence ◽

Phylogenetic Analyses ◽

Hepatitis E ◽

The United States ◽

Serum Samples ◽

History Of ◽

Swine Hepatitis ◽

Acute Hepatitis E ◽

Swine Strain

Recently, we found that more than 10% of the cases of acute non-A, non-B, non-C hepatitis in Taiwan were caused by a novel strain of hepatitis E virus (HEV). Since none of these patients had a history of travel to areas where HEV is endemic, the source of transmission remains unclear. The recent discovery of a swine HEV in herd pigs in the United States has led us to speculate that HEV may also circulate in herd pigs in Taiwan and may serve as a reservoir for HEV in Taiwan. Of 275 herd pigs obtained from 10 pig farms in Taiwan, 102 (37%) were seropositive for serum anti-HEV immunoglobulin G (IgG). A 185-bp genomic sequence within the ORF-2 of the HEV genome was amplified and cloned from serum samples of an anti-HEV positive pig and subsequently from serum samples of a patient with acute hepatitis E. Sequence comparison revealed that the swine and human isolates of HEV share 97.3% identity. Phylogenetic analyses further showed that the Taiwan swine and human isolates of HEV form a distinct branch divergent from all other known strains of HEV, including the U.S. swine strain. To examine the potential risk of cross-species transmission of swine HEV to humans, the seroprevalences of anti-HEV IgG in 30 swine handlers, 20 pork dealers, and 50 control subjects were assessed and were found to be 26.7, 15, and 8%, respectively (for swine handlers versus controls,P = 0.048). Our findings may help provide an understanding of the modes of HEV transmission and may also raise potential public health concerns for HEV zoonosis.

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Hepatitis E Virus Infection in an Immigrant to the United States

Southern Medical Journal ◽

10.1097/00007611-199610000-00012 ◽

1996 ◽

Vol 89 (10) ◽

pp. 994-996 ◽

Cited By ~ 7

Author(s):

DAVID L. SMALLEY ◽

SUSAN C. BREWER ◽

GEORGE J. DAWSON ◽

CHARLES KYRK ◽

BRADFORD WATERS

Keyword(s):

United States ◽

Virus Infection ◽

Hepatitis E Virus ◽

Hepatitis E ◽

The United States

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579 – Exploring Risk Factors for Exposure to Hepatitis E Virus in Kidney Transplant Recipients from a Single Center in the United States

Gastroenterology ◽

10.1016/s0016-5085(19)40001-2 ◽

2019 ◽

Vol 156 (6) ◽

pp. S-1207

Author(s):

Paul Wasuwanich ◽

Supharerk Thawillarp ◽

Wikrom Karnsakul

Keyword(s):

United States ◽

Risk Factors ◽

Kidney Transplant ◽

Hepatitis E Virus ◽

Hepatitis E ◽

The United States ◽

Transplant Recipients ◽

Single Center ◽

Kidney Transplant Recipients

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290. Hepatitis E Virus Serostatus: A Retrospective Assessment of Demographics and Comorbidities to Assess High-risk Populations

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.365 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S158-S158

Author(s):

Eric C Stone ◽

Zerelda Esquer Garrigos ◽

Muhammad R Sohail ◽

Raymund R Razonable ◽

John C O’Horo

Keyword(s):

United States ◽

Liver Disease ◽

Hepatitis E Virus ◽

Kidney Diseases ◽

Hepatitis E ◽

The United States ◽

Population Based ◽

Positive Serology ◽

Serologic Testing ◽

One Year

Abstract Background Demographic and epidemiologic characteristics of Hepatitis E virus (HEV) infected patients in the United States are not well-described. HEV infection may result in severe complications and lead to chronic infection and cirrhosis, especially in immunocompromised patients. There are no widely accepted guidelines for HEV screening and testing in the United States. Identifying traits of known seropositive patients and comorbidities may inform better screening and prevention strategies. In this study, we describe rates of liver disease, transplant status, chronic kidney diseases, and diabetes mellitus among patients serologically tested for HEV at our institution. Methods We retrospectively reviewed all patients for whom HEV IgM or IgG serologic testing was performed across the Mayo Clinic enterprise using the Advanced Cohort Explorer tool. For patients with any documented HEV serologic test, we abstracted baseline patient characteristics and underlying comorbidities at the time of testing. We then grouped subjects according to serologic testing results by antibody type. Survival at one year from date of testing was also assessed. Results A total of 979 unique subjects were identified. The preponderance of subjects was Caucasian (781, 79.8%). Of subjects tested for HEV with serology, 123 (12.6%) had any positive serology. Breakdown of baseline characteristics and selected comorbidities are summarized in Table 1. The largest proportion of subjects, 458 (46.8%), were both IgG and IgM negative and 432 subjects received only IgM or IgG testing. Liver disease was more prevalent in patients with positive vs. negative testing (5.8% vs. 2.1%) as was higher age (average 55.1 years vs. 52.2). One-year survival was similar in all groups. Conclusion HEV serology is not commonly tested. Among those tested, seropositivity is uncommon. Our data show higher HEV seropositivity in older adults, which may represent increase risk of exposure over time. Higher percentage of positive testing was also observed in subjects with liver disease, which may indicate a possible etiologic association. Further population-based studies are needed to estimate prevalence of HEV infection and associated liver disease, outcomes in infected patients, and indications for testing in at-risk populations. Disclosures All authors: No reported disclosures.

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