Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model

Tpe. Williams et al., Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model, J CLIN MICR, 39(9), 2001, pp. 3040-3046
Citations number
Categorie Soggetti
Clinical Immunolgy & Infectious Disease",Microbiology
Journal title
ISSN journal
0095-1137 → ACNP
Year of publication
3040 - 3046
SICI code
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 sys tem and a practical animal model, the mechanisms of REV pathogenesis and re plication are poorly understood. Our recent identification of swine HEV fro m pigs affords us an opportunity to systematically study HEV replication an d pathogenesis in a swine model. In an early study, we experimentally infec ted 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 intraveno usly 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. Th e 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 necropsie d at 3, 7, 14, 20, 27, and 55 days postinoculation (DPI). Thirteen differen t types of tissues and organs were collected from each necropsied animal. R everse transcriptase PCR (RT-PCR) was used to detect the presence of positi ve-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 detec ted in almost every type of tissue at some time point during the viremic pe riod 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 det ected primarily in the small intestines, lymph nodes, colons, and livers. O ur results indicate that HEV replicates in tissues other than the liver. Th e data from this study may have important implications for HEV pathogenesis , xenotransplantation, and the development of an in vitro cell culture syst em for HEV.