Source: IOWA STATE UNIVERSITY submitted to NRP
COMPARATIVE PATHOGENESIS OF HEPATITIS E VIRUSES FROM PIGS AND CHICKENS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
ANIMAL HEALTH
Reporting Frequency
Annual
Accession No.
0192184
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Oct 1, 2001
Project End Date
Sep 30, 2004
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
IOWA STATE UNIVERSITY
S. AND 16TH ELWOOD
AMES,IA 50011
Performing Department
VETERINARY MEDICINE
Non Technical Summary
Pigs are now considered a potential reservoir and source for HEV infections of humans. This work will advance the understanding of the mechanism of HEV-induced hepatitis, further refine the swine model for HEV infection, and perhaps provide insight into the treatment of clinical HEV infection in humans and pigs and chickens.
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113510110140%
3113510116030%
3113510117030%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3510 - Swine, live animal;

Field Of Science
1101 - Virology; 1160 - Pathology; 1170 - Epidemiology;
Goals / Objectives
Pigs are now considered a potential reservoir and source for HEV infection of humans. There is also increased concern over the risk of transmission of HEV when pig organs or cells are used for xenotransplantation. It is important that we better understand the pathogenesis of HEV infection and mechanism of HEV-induced hepatocellular damage. Knowing the status of comparative virulence among the isolates of swine HEV would provide basic knowledge in order to further study the molecular basis of HEV pathogenecity. The proposed work will advance the understanding of the mechanism of HEV-induced hepatitis, broaden the information of HEV interspecies transmission, further refine the swine model for human HEV infection, and perhaps provide insight into the development of vaccines for prevention and therapeutic agents for treatment of clinical HEV infection in humans and pigs and poultry. all the research to date has been done with the prototype strain of U.S. swine HEV. We have recently detected swine HEV in pigs from several different U.S. locations by RT-PCR. In addition, an avian HEV-like virus has been isolated from chickens in the U.S. To some extent, these recent swine HEV isolates and the avian HEV are genetically distinct from human HEV strains, the prototype swine HEV strain, and among each other. Our hypothesis is that different isolates of swine HEV and an avian HEV differ in pathogenicity. Our specific aims are to determine: i) if isolates of swine HEV collected from pigs in different geographical regions of the U.S. differ in virulence; ii) if a chicken HEV isolate replicates in pigs and induces clinical disease and hepatitis lesions; and iii) TNFa mRNA expression in HEV-infected livers in associated with apoptosis of hepatocytes.
Project Methods
Essentially, all the research to date has been done with the prototype strain of U.S. swine HEV. We have recently detected swine HEV in pigs from several different U.S. locations by RT-PCR. In addition, an avian HEV-like virus has been isolated from chickens in the U.S. To some extent, these recent swine HEV isolates and the avian HEV are genetically distinct from human HEV strains, the prototype swine HEV strain, and among each other. We will use different isolates of swine HEV and chicken HEV as inocula. HEV-free SPF pigs will be experimentally inoculated with an individual isolate and the virulence will be determined by comparing clinical scores and liver lesion scores to the prototype swine HEV strain. We will use RT-PCR to determine TNFa mRNA expression in HEV-infected livers, and Terminal Transferase-mediated dUTP Nick End-Labeling (TUNEL) assay to assess the presence and amount of hepatocellular apoptosis.

Progress 01/01/01 to 12/31/01

Outputs
Swine hepatitis E virus (HEV) was discovered by our group in 1997. Later in 1997, a human strain of HEV was discovered in the U.S. and found to be closely related to the US swine HEV. Subsequently, we demonstrated interspecies transmission of HEV by experimental infection of non-human primates with swine HEV resulting in clinical hepatitis, and experimental infection of pigs with the US-2 strain of human HEV. Pigs, whether infected with the human or swine strain of HEV, develop multifocal lymphoplasmacytic hepatitis lesions and shed virus in bile and feces for at least 5 weeks. Recently, we demonstrated in a swine bioassay that HEV could be transmitted via intravenous inoculation of naive animals with pig liver tissue homogenates or feces from HEV-infected pigs. Pigs are now considered a potential reservoir and source for HEV infections of humans. There is also increased concern over the risk of transmission of HEV when pig organs or cells are used for xenotransplantation. Essentially, all the research to date has been done with the prototype strain of U.S. swine HEV. We have recently detected swine HEV in pigs from several different U.S. locations by RT-PCR. In addition, an avian HEV-like virus has been isolated from chickens in the U.S. To some extent, these recent swine HEV isolates and the avian HEV are genetically distinct from human HEV strains, the prototype swine HEV strain, and among each other. Our hypothesis is that different isolates of swine HEV and an avian HEV differ in pathogenicity. We will use different isolates of swine HEV and chicken HEV as inocula. HEV-free SPF pigs will be experimentally inoculated with an individual isolate and the virulence will be determined by comparing clinical scores and liver lesion scores to the prototype swine HEV strain. We will use RT-PCR to determine TNF mRNA expression in HEV-infected livers, and Terminal Transferase-mediated dUTP Nick End-Labeling (TUNEL) assay to assess the presence and amount of hepatocellular apoptosis.

Impacts
This work will advance the understanding of the mechanism of HEV-induced hepatitis, determine if chicken HEV can infect pigs, further refine the swine model for HEV infection, and perhaps provide insight into the treatment of clinical HEV infection in humans and pigs and chickens.

Publications

  • No publications reported this period