This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Williams, T. P. E.
Right arrow Articles by Meng, X. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Williams, T. P. E.
Right arrow Articles by Meng, X. J.

 Previous Article  |  Next Article 

Journal of Clinical Microbiology, September 2001, p. 3040-3046, Vol. 39, No. 9
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.9.3040-3046.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Evidence of Extrahepatic Sites of Replication of the Hepatitis E Virus in a Swine Model

T. P. E. Williams,1 C. Kasorndorkbua,2 P. G. Halbur,2 G. Haqshenas,1 D. K. Guenette,1 T. E. Toth,1 and X. J. Meng1,*

Center for Molecular Medicine and Infection Diseases, Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia,1 and Department of Veterinary Diagnostic and Animal Production Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa2

Received 4 April 2001/Returned for modification 12 June 2001/Accepted 23 June 2001

Hepatitis E virus (HEV) is the major cause of enterically transmitted non-A, non-B hepatitis in many developing countries and is also endemic in many industrialized countries. Due to the lack of an effective cell culture system and a practical animal model, the mechanisms of HEV pathogenesis and replication are poorly understood. Our recent identification of swine HEV from pigs affords us an opportunity to systematically study HEV replication and pathogenesis in a swine model. In an early study, we experimentally infected specific-pathogen-free pigs with two strains of HEV: swine HEV and the US-2 strain of human HEV. Eighteen pigs (group 1) were inoculated intravenously with swine HEV, 19 pigs (group 2) were inoculated with the US-2 strain of human HEV, and 17 pigs (group 3) were used as uninoculated controls. The clinical and pathological findings have been previously reported. In this expanded study, we aim to identify the potential extrahepatic sites of HEV replication using the swine model. Two pigs from each group were necropsied at 3, 7, 14, 20, 27, and 55 days postinoculation (DPI). Thirteen different types of tissues and organs were collected from each necropsied animal. Reverse transcriptase PCR (RT-PCR) was used to detect the presence of positive-strand HEV RNA in each tissue collected during necropsy at different DPI. A negative-strand-specific RT-PCR was standardized and used to detect the replicative, negative strand of HEV RNA from tissues that tested positive for the positive-strand RNA. As expected, positive-strand HEV RNA was detected in almost every type of tissue at some time point during the viremic period between 3 and 27 DPI. Positive-strand HEV RNA was still detectable in some tissues in the absence of serum HEV RNA from both swine HEV- and human HEV-inoculated pigs. However, replicative, negative-strand HEV RNA was detected primarily in the small intestines, lymph nodes, colons, and livers. Our results indicate that HEV replicates in tissues other than the liver. The data from this study may have important implications for HEV pathogenesis, xenotransplantation, and the development of an in vitro cell culture system for HEV.

* Corresponding author. Mailing address: Center for Molecular Medicine and Infectious Diseases, Virginia Polytechnic Institute and State University, 1410 Prices Fork Rd., Blacksburg, VA 24061-0342. Phone: (540) 231-6912. Fax: (540) 231-3476. E-mail: xjmeng{at}vt.edu.

Journal of Clinical Microbiology, September 2001, p. 3040-3046, Vol. 39, No. 9
0095-1137/01/$04.00+0   DOI: 10.1128/JCM.39.9.3040-3046.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Pudupakam, R. S., Huang, Y. W., Opriessnig, T., Halbur, P. G., Pierson, F. W., Meng, X. J. (2009). Deletions of the Hypervariable Region (HVR) in Open Reading Frame 1 of Hepatitis E Virus Do Not Abolish Virus Infectivity: Evidence for Attenuation of HVR Deletion Mutants In Vivo. J. Virol. 83: 384-395 [Abstract] [Full Text]  
  • Billam, P., Pierson, F. W., Li, W., LeRoith, T., Duncan, R. B., Meng, X. J. (2008). Development and Validation of a Negative-Strand-Specific Reverse Transcription-PCR Assay for Detection of a Chicken Strain of Hepatitis E Virus: Identification of Nonliver Replication Sites. J. Clin. Microbiol. 46: 2630-2634 [Abstract] [Full Text]  
  • Takahashi, M., Tanaka, T., Azuma, M., Kusano, E., Aikawa, T., Shibayama, T., Yazaki, Y., Mizuo, H., Inoue, J., Okamoto, H. (2007). Prolonged Fecal Shedding of Hepatitis E Virus (HEV) during Sporadic Acute Hepatitis E: Evaluation of Infectivity of HEV in Fecal Specimens in a Cell Culture System. J. Clin. Microbiol. 45: 3671-3679 [Abstract] [Full Text]  
  • NAKAI, I., KATO, K., MIYAZAKI, A., YOSHII, M., LI, T.-C., TAKEDA, N., TSUNEMITSU, H., IKEDA, H. (2006). DIFFERENT FECAL SHEDDING PATTERNS OF TWO COMMON STRAINS OF HEPATITIS E VIRUS AT THREE JAPANESE SWINE FARMS. Am J Trop Med Hyg 75: 1171-1177 [Abstract] [Full Text]  
  • Kasorndorkbua, C., Opriessnig, T., Huang, F. F., Guenette, D. K., Thomas, P. J., Meng, X.-J., Halbur, P. G. (2005). Infectious Swine Hepatitis E Virus Is Present in Pig Manure Storage Facilities on United States Farms, but Evidence of Water Contamination Is Lacking. Appl. Environ. Microbiol. 71: 7831-7837 [Abstract] [Full Text]  
  • Ahn, J.-m., Kang, S.-G., Lee, D.-Y., Shin, S. J., Yoo, H. S. (2005). Identification of Novel Human Hepatitis E Virus (HEV) Isolates and Determination of the Seroprevalence of HEV in Korea. J. Clin. Microbiol. 43: 3042-3048 [Abstract] [Full Text]  
  • Billam, P., Huang, F. F., Sun, Z. F., Pierson, F. W., Duncan, R. B., Elvinger, F., Guenette, D. K., Toth, T. E., Meng, X. J. (2005). Systematic Pathogenesis and Replication of Avian Hepatitis E Virus in Specific-Pathogen-Free Adult Chickens. J. Virol. 79: 3429-3437 [Abstract] [Full Text]  
  • Huang, Y. W., Haqshenas, G., Kasorndorkbua, C., Halbur, P. G., Emerson, S. U., Meng, X. J. (2005). Capped RNA Transcripts of Full-Length cDNA Clones of Swine Hepatitis E Virus Are Replication Competent When Transfected into Huh7 Cells and Infectious When Intrahepatically Inoculated into Pigs. J. Virol. 79: 1552-1558 [Abstract] [Full Text]  
  • Kasorndorkbua, C., Guenette, D. K., Huang, F. F., Thomas, P. J., Meng, X.-J., Halbur, P. G. (2004). Routes of Transmission of Swine Hepatitis E Virus in Pigs. J. Clin. Microbiol. 42: 5047-5052 [Abstract] [Full Text]  
  • Sun, Z. F., Larsen, C. T., Huang, F. F., Billam, P., Pierson, F. W., Toth, T. E., Meng, X. J. (2004). 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. J. Clin. Microbiol. 42: 2658-2662 [Abstract] [Full Text]  
  • Sun, Z. F., Larsen, C. T., Dunlop, A., Huang, F. F., Pierson, F. W., Toth, T. E., Meng, X.-J. (2004). Genetic identification of avian hepatitis E virus (HEV) from healthy chicken flocks and characterization of the capsid gene of 14 avian HEV isolates from chickens with hepatitis-splenomegaly syndrome in different geographical regions of the United States. J. Gen. Virol. 85: 693-700 [Abstract] [Full Text]  
  • Yazaki, Y., Mizuo, H., Takahashi, M., Nishizawa, T., Sasaki, N., Gotanda, Y., Okamoto, H. (2003). Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. J. Gen. Virol. 84: 2351-2357 [Abstract] [Full Text]  
  • Choi, I.-S., Kwon, H.-J., Shin, N.-R., Yoo, H. S. (2003). Identification of Swine Hepatitis E Virus (HEV) and Prevalence of Anti-HEV Antibodies in Swine and Human Populations in Korea. J. Clin. Microbiol. 41: 3602-3608 [Abstract] [Full Text]  
  • Huang, F. F., Haqshenas, G., Shivaprasad, H. L., Guenette, D. K., Woolcock, P. R., Larsen, C. T., Pierson, F. W., Elvinger, F., Toth, T. E., Meng, X. J. (2002). Heterogeneity and Seroprevalence of a Newly Identified Avian Hepatitis E Virus from Chickens in the United States. J. Clin. Microbiol. 40: 4197-4202 [Abstract] [Full Text]  
  • Haqshenas, G., Huang, F. F., Fenaux, M., Guenette, D. K., Pierson, F. W., Larsen, C. T., Shivaprasad, H. L., Toth, T. E., Meng, X. J. (2002). The putative capsid protein of the newly identified avian hepatitis E virus shares antigenic epitopes with that of swine and human hepatitis E viruses and chicken big liver and spleen disease virus. J. Gen. Virol. 83: 2201-2209 [Abstract] [Full Text]  
  • Huang, F. F., Haqshenas, G., Guenette, D. K., Halbur, P. G., Schommer, S. K., Pierson, F. W., Toth, T.E., Meng, X. J. (2002). 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. J. Clin. Microbiol. 40: 1326-1332 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»