Comparative Pathogenesis of Infection of Pigs with Hepatitis E Viruses Recovered from a Pig and a Human

Abstract

Specific-pathogen-free pigs were inoculated with one of two hepatitis E viruses (HEV) (one recovered from a pig and the other from a human) to study the relative pathogenesis of the two viruses in swine. Fifty-four pigs were randomly assigned to three groups. Seventeen pigs in group 1 served as uninoculated controls, 18 pigs in group 2 were intravenously inoculated with the swine HEV recovered from a pig in the United States, and 19 pigs in group 3 were intravenously inoculated with the US-2 strain of human HEV recovered from a hepatitis patient in the United States. Two to four pigs from each group were necropsied at 3, 7, 14, 20, 27, or 55 days postinoculation (DPI). Evidence of clinical disease or elevation of liver enzymes or bilirubin was not found in pigs from any of the three groups. Enlarged hepatic and mesenteric lymph nodes were observed in both HEV-inoculated groups. Multifocal lymphoplasmacytic hepatitis was observed in 9 of 17, 15 of 18, and 16 of 19 pigs in groups 1 to 3, respectively. Focal hepatocellular necrosis was observed in 5 of 17, 10 of 18, and 13 of 19 pigs in groups 1 to 3, respectively. Hepatitis lesions were very mild in group 1 pigs, mild to moderate in group 2 pigs, and moderate to severe in group 3 pigs. Hepatic inflammation and hepatocellular necrosis peaked in severity at 20 DPI and were still moderately severe at 55 DPI in the group inoculated with human HEV. Hepatitis lesions were absent or nearly resolved by 55 DPI in the swine-HEV-inoculated pigs. All HEVinoculated pigs seroconverted to anti-HEV immunoglobulin G. HEV RNA was detected by reverse transcriptase PCR in feces, liver tissue, and bile of pigs in both HEV-inoculated groups from 3 to 27 DPI. Based on evaluation of microscopic lesions, the US-2 strain of human HEV induced more severe and persistent hepatic lesions in pigs than did swine HEV. Pig livers or cells from the livers of HEV-infected pigs may represent a risk for transmission of HEV from pigs to human xenograft recipients. Since HEV was shed in the feces of infected pigs, exposure to feces from infected pigs represents a risk for transmission of HEV, and pigs should be considered a reservoir for HEV.Hepatitis E virus (HEV) is the leading cause of enterically transmitted non-A, non-B hepatitis in people in many developing countries (21,28,30). Transmission is thought to be primarily by the fecal-oral route, and waterborne epidemics are characteristic of hepatitis E (1, 28, 30). Clinical disease due to HEV infection is rarely diagnosed in industrialized countries, and most cases of HEV infection in industrialized countries occur in people who have traveled to regions where the disease is endemic (10,21,28,30). Clinical cases occur predominantly in developing countries in Asia, Africa, and Mexico (1, 2, 28, 30). However, sporadic cases of acute hepatitis E in people in the United States and other industrialized countries have recently been reported (7,8,11,18,20,22,31,32,42). Hepatitis E generally affects young adults and usually is not fatal, although mortality r...

Distribution and Propagation of Hepatitis E Virus in Experimentally Infected Swine

“…RNA was observed only transiently in intravenously inoculated pig A at 7-11 dpi at low copy numbers (less than 1000 copies/ml), although it was not a mutual observation in all inoculated pigs during the observation period [27]. On the other hand, considerably high copy numbers of HEV-RNAs were detected in the feces from HEV-infected pigs.…”

Genetic changes in hepatitis E virus of subtype 1a in patients with sporadic acute hepatitis E in Kathmandu, Nepal, from 1997 to 2002

“…The observed changing prevalence of the five 1a clusters according to the year of disease onset suggests that the genetic variability of HEV in a community is due to continuously occurring genetic changes and that takeover of existing strain(s) possibly occurs by the selected variant having an advantage in transmission in the community or variant(s) that was imported from other communities. An alternative hypothesis for the variability observed in field isolates is ongoing evolution in alternative host species, since increasing evidence has indicated that hepatitis E is a zoonosis (Harrison, 1999;Erker et al, 1999;Meng, 2000;Meng et al, 1997Meng et al, , 1998Halbur et al, 2001;Okamoto et al, 2001;Smith, 2001;Takahashi et al, 2003;Tei et al, 2003), whether or not hepatitis E is common in the resident human population.…”

Generation and Infectivity Titration of an Infectious Stock of Avian Hepatitis E Virus (HEV) in Chickens and Cross-Species Infection of Turkeys with Avian HEV

“…It has previously been shown that swine HEV infects nonhuman primates and that human HEV infects pigs (6,16). Therefore, after obtaining a standard infectious stock of avian HEV, we attempted to experimentally infect another avian species, turkeys, with avian HEV from a chicken.…”

“…Cross-species infection by swine and human HEVs has been demonstrated, as a human HEV strain infected specific-pathogen-free (SPF) pigs and a swine HEV strain infected nonhuman primates (6,16). Anti-HEV antibodies have also been detected in many animal species, and hepatitis E is considered a zoonosis (4,12,17,18,30).…”