scholarly journals Systematic Pathogenesis and Replication of Avian Hepatitis E Virus in Specific-Pathogen-Free Adult Chickens

2005 ◽  
Vol 79 (6) ◽  
pp. 3429-3437 ◽  
Author(s):  
P. Billam ◽  
F. F. Huang ◽  
Z. F. Sun ◽  
F. W. Pierson ◽  
R. B. Duncan ◽  
...  

ABSTRACT Hepatitis E virus (HEV) is an important human pathogen. Due to the lack of a cell culture system and a practical animal model for HEV, little is known about its pathogenesis and replication. The discovery of a strain of HEV in chickens, designated avian HEV, prompted us to evaluate chickens as a model for the study of HEV. Eighty-five 60-week-old specific-pathogen-free chickens were randomly divided into three groups. Group 1 chickens (n = 28) were each inoculated with 5 × 104.5 50% chicken infectious doses of avian HEV by the oronasal route, group 2 chickens (n = 29) were each inoculated with the same dose by the intravenous (i.v.) route, and group 3 chickens (n = 28) were not inoculated and were used as controls. Two chickens from each group were necropsied at 1, 3, 5, 7, 10, 13, 16, 20, 24, 28, 35, and 42 days postinoculation (dpi), and the remaining chickens were necropsied at 56 dpi. Serum, fecal, and various tissue samples, including liver and spleen samples, were collected at each necropsy for pathological and virological testing. By 21 dpi, all oronasally and i.v. inoculated chickens had seroconverted. Fecal virus shedding was detected variably from 1 to 20 dpi for the i.v. group and from 10 to 56 dpi for the oronasal group. Avian HEV RNA was detected in serum, bile, and liver samples from both i.v. and oronasally inoculated chickens. Gross liver lesions, characterized by subcapsular hemorrhages or enlargement of the right intermediate lobe, were observed in 7 of 28 oronasally and 7 of 29 i.v. inoculated chickens. Microscopic liver lesions were mainly lymphocytic periphlebitis and phlebitis. The lesion scores were higher for oronasal (P = 0.0008) and i.v. (P = 0.0029) group birds than for control birds. Slight elevations of the plasma liver enzyme lactate dehydrogenase were observed in infected chickens. The results indicated that chickens are a useful model for studying HEV replication and pathogenesis. This is the first report of HEV transmission via its natural route in a homologous animal model.

Virus Genes ◽  
2018 ◽  
Vol 54 (4) ◽  
pp. 587-590 ◽  
Author(s):  
Sang-Hoon Han ◽  
Byung-Joo Park ◽  
Hee-Seop Ahn ◽  
Yong-Hyun Kim ◽  
Hyeon-Jeong Go ◽  
...  

2005 ◽  
Vol 86 (9) ◽  
pp. 2585-2593 ◽  
Author(s):  
F. F. Huang ◽  
F. W. Pierson ◽  
T. E. Toth ◽  
X. J. Meng

Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important human pathogen. Increasing evidence indicates that hepatitis E is a zoonosis. Avian HEV was recently discovered in chickens with hepatitis–splenomegaly syndrome in the USA. Like swine HEV from pigs, avian HEV is also genetically and antigenically related to human HEV. The objective of this study was to construct and characterize an infectious cDNA clone of avian HEV for future studies of HEV replication and pathogenesis. Three full-length cDNA clones of avian HEV, pT7-aHEV-5, pT7G-aHEV-10 and pT7G-aHEV-6, were constructed and their infectivity was tested by in vitro transfection of leghorn male hepatoma (LMH) chicken liver cells and by direct intrahepatic inoculation of specific-pathogen-free (SPF) chickens with capped RNA transcripts from the three clones. The results showed that the capped RNA transcripts from each of the three clones were replication competent when transfected into LMH cells as demonstrated by detection of viral antigens with avian HEV-specific antibodies. SPF chickens intrahepatically inoculated with the capped RNA transcripts from each of the three clones developed active avian HEV infections as evidenced by seroconversion to avian HEV antibodies, viraemia and faecal virus shedding. The infectivity was further confirmed by successful infection of naïve chickens with the viruses recovered from chickens inoculated with the RNA transcripts. The results indicated that all three cDNA clones of avian HEV are infectious both in vitro and in vivo. The availability of these infectious clones for a chicken strain of HEV now affords an opportunity to study the mechanisms of HEV cross-species infection and tissue tropism by constructing chimeric viruses among human, swine and avian HEVs.


2006 ◽  
Vol 80 (13) ◽  
pp. 6721-6721
Author(s):  
P. Billam ◽  
F. F. Huang ◽  
Z. F. Sun ◽  
F. W. Pierson ◽  
R. B. Duncan ◽  
...  

2008 ◽  
Vol 80 (8) ◽  
pp. 1379-1386 ◽  
Author(s):  
A.R. Feagins ◽  
T. Opriessnig ◽  
Y.W. Huang ◽  
P.G. Halbur ◽  
X.J. Meng

2004 ◽  
Vol 85 (6) ◽  
pp. 1609-1618 ◽  
Author(s):  
F. F. Huang ◽  
Z. F. Sun ◽  
S. U. Emerson ◽  
R. H. Purcell ◽  
H. L. Shivaprasad ◽  
...  

Avian hepatitis E virus (avian HEV), recently identified from a chicken with hepatitis–splenomegaly syndrome in the United States, is genetically and antigenically related to human and swine HEVs. In this study, sequencing of the genome was completed and an attempt was made to infect rhesus monkeys with avian HEV. The full-length genome of avian HEV, excluding the poly(A) tail, is 6654 bp in length, which is about 600 bp shorter than that of human and swine HEVs. Similar to human and swine HEV genomes, the avian HEV genome consists of a short 5′ non-coding region (NCR) followed by three partially overlapping open reading frames (ORFs) and a 3′NCR. Avian HEV shares about 50 % nucleotide sequence identity over the complete genome, 48–51 % identity in ORF1, 46–48 % identity in ORF2 and only 29–34 % identity in ORF3 with human and swine HEV strains. Significant genetic variations such as deletions and insertions, particularly in ORF1 of avian HEV, were observed. However, motifs in the putative functional domains of ORF1, such as the helicase and methyltransferase, were relatively conserved between avian HEV and mammalian HEVs, supporting the conclusion that avian HEV is a member of the genus Hepevirus. Phylogenetic analysis revealed that avian HEV represents a branch distinct from human and swine HEVs. Swine HEV infects non-human primates and possibly humans and thus may be zoonotic. An attempt was made to determine whether avian HEV also infects across species by experimentally inoculating two rhesus monkeys with avian HEV. Evidence of virus infection was not observed in the inoculated monkeys as there was no seroconversion, viraemia, faecal virus shedding or serum liver enzyme elevation. The results from this study confirmed that avian HEV is related to, but distinct from, human and swine HEVs; however, unlike swine HEV, avian HEV is probably not transmissible to non-human primates.


2007 ◽  
Vol 88 (5) ◽  
pp. 1532-1537 ◽  
Author(s):  
H. Guo ◽  
E. M. Zhou ◽  
Z. F. Sun ◽  
X.-J. Meng

Avian hepatitis E virus (HEV) is genetically and antigenically related to human HEV. Vertical transmission of HEV has been reported in humans, but not in other animals. In this study, we showed that avian HEV could be detected in chicken egg-white samples. Subsequently, avian HEV in egg white was found to be infectious, as evidenced by the appearance of viraemia, faecal virus shedding and seroconversion in chickens inoculated with avian HEV-positive egg white, but not in chickens inoculated with HEV-negative egg white. To further assess the possibility of vertical transmission of avian HEV, batches of embryonated eggs from infected hens were hatched, and hatched chicks were monitored for evidence of avian HEV infection. However, no virus was detected in samples collected from the hatched chicks throughout this study, suggesting that avian HEV could not complete the vertical transmission cycle. The possible implications of our findings are also discussed.


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