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Geographical Pathology of Duck Livers Infected with Duck Hepatitis B Virus from Chiba and Shimane in Japan and Shanghai in China'

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Geographical Pathology of Duck Livers Infected with Duck Hepatitis B Virus from Chiba and Shimane in Japan and Shanghai in China' ICANCER RESEARCH 48, 1319-1325, March 1, 19881 Geographical Pathology of Duck Livers Infected with Duck Hepatitis B Virus from Chiba and Shimane in Japan and Shanghai in China' Toshikazu Uchida,2 Koyu Suzuki, Masahiro Arli, Toshio Shikata, Ryo Fukuda, and Yixun Tao First Department ofPathology, Nihon University, School ofMedicine, Tokyo,Japan IT U., K. S., M. A., T. 5.1; Department ofMedkine, Shimane Medical &hool, Shimane, Japan IR. F.); and Department ofLaboratory Sciences,Shanghai SecondMedical College,Shanghai, China IT. T.J ABSTRACF lular carcinomas after a long period of chronic host infection, and viral I@NA sequences are frequently integrated into the In order to evaluate geographicaldifferencesin the liver pathologyof genomes of carcinoma cells (3, 8, 9). The hepatocellular carci ducks Infected with duck hepatitis B virus (DHBV), ducks in Chiba and nomas are usually associated with chronic hepatitis or cirrhosis Shhnane4Japan,and Shanghai, China, were investigated.The numbers (DHBV positIve/negative)andthe maximumageof the ducksexamined in the noncarcinomatous area oflivers of virus-carrier hosts (3, were 18/10 at 19 IflO, 15/I at 3 yr 4 mo, and 72/27 at 18 mo, respectively. 8, 9). DHBV infectionwas InducedexperImentallyinducks fromChibaand In contrast to mammalian hepadnaviruses, the occurrence of Shimane but was present congenitally in those from Shanghai. Ducks pathological changes due to DHBV infection is controversial. were examined regarding liver function tests, conventional histology, Actually, in our construct of persistent DHBV infection the immunohistology, electron microscopy, and molecular hybridization for ducks did not show any significant hepatitis activity histologi DHBV DNA in the serumandliver. cally (6), which conflicts with the reports of other laboratories There was no significant difference between DHBV-positlve and (10—12).The latter reported that DHBV infection provoked -negativeducks in bilirubin and transaminaseand alkaline phosphatase chronic hepatitis, cirrhosis, and hepatocellular carcinoma. activities in the sen. Histologically, while the livers ofducks from Chiba and Shimane did not show necrolnflammatory(hepatitis) activity, those Interestingly, the most advanced liver disorders were reported fromShanghai frequentlydid (523%). Necroinflammatoryactivityof the in the ducks from Shanghai rather than in those from Japan Shanghaiducks was presentalmost equally in both DHBV-positive and and the United States. Therefore the possibility is raised that -negative livers. The livers ofShnngb*i ducks but not the other two areas the variation in the histological change ofDHBV-positive livers often (8.3%) had ground-glass inclusions which corresponded ultrastruc may reflect the difference in strains of ducks, the presence of turally to numerous virus particles in the dilated clsternae of the prolif some subtype of DHBV, or environmental factors, including erated endoplasmic reticulum. No advanced liver disease, such as clrrho hepatotropic agents and diet. The present study was performed sis or hepatocellular carcinoma, was observed. There was no significant to investigate the putative differences in liver function, liver difference in the amount of DHBV DNA in the sera or in Its pattern in morphology, and virology between ducks from Japan and the liver tissue among ducks of the three areas. In addition, the livers of Shanghai. Chiba ducks frequently had amyloidosis, while those of Shanghai ducks werecontaminatedwith parasites. In conclusion,DHBV infectiondid not appearto provokesignificant MATERIALS AND METhODS hepatitis activity or advancedliver diseaseIn the examinedducks of all three areas, and the DHBV-positivelivers from Shanghai ducks showed Ducks and the Transmission of DHBV a differentmorphologicalappearancefromthoseof the othertwoareas. This variation might reflect the difference in the strain ofducks, subtypes DucksfromChiba and Shimane.The ducks used werewhite-feathered of DHBV, environmentalfactors,or a combinationofthese influences. Pekin group (Anas domesticus) adults weighing ‘@-3kg.The ducklings were purchased immediately after hatching from commercial farms in Chiba Prefecture (Chiba ducks) and Shimane Prefecture (Shimane INTRODUcTION ducks). Chiba is located in central Japan, and Shimane is in the South. The farms showed an absence ofDHBV infections. The ducklings were DHBV3 was discovered in 1980 (1) and constitutes a member inoculated i.v. with 50 @zlor25 @lofDHBV-positive serum (“-4xiO@ of the family of hepadnavirus (2) which also includes the complete virions per ml as estimated from DHBV DNA hybridization hepatitis B virus, woodchuck hepatitis virus (3), and ground assay).This inoculation procedure on the same day as hatching pro squirrel hepatitis virus (4). Infection ofDHBV in the ducks was duced 100% successful persistent viremia. Negative control ducklings achieved by congenital transmission from DHBV-positive were not inoculated with any serum. mother ducks to their offspring (5), or by experimental inocu The DHBV-positive serum for the Chiba and Shimane ducks was lation of DHBV-positive serum into the ducklings within 3 originallyderivedfromPekinducksfrom Philadelphia,PA,andTaipei, days after hatching (6, 7). The experimental inoculation of Taiwan, respectively. The ducks were first kept indoors in cages for 1 DHBV in the duckling 5 days after hatching resulted in tran to 3 mo and then outdoors, and they were fed ad libitum a standard sient viremia associated with mild acute hepatitis features (7). commercial diet. They were sacrificed at ages of from 14 to 18 mo for Chiba ducks and 3 yr to 3 yr 4 mo for Shimane ducks. Mammalian hepadnaviruses are known to cause hepatocel The serawereassayedfor DHBV DNA and liverfunctiontests, and the tissues,forDHBV DNA, conventionalhistochemistry,immunohis Received4/20/87; revised 11/23/87; accepted 12/3/87. tochemistry, and electron microscopy. The costsof publicationof this article were defrayedin part by the payment Shanghai Ducks. With light brown feathers, these 1.5-kg adults are of pagecharges.This article must thereforebe herebymarkedadvertisementin locally known as “eggducks.―Ninety-nine ducklings aged 12 to 18 mo accordancewith 18 U.S.C. Section 1734 solely to indicate this fact. were purchased from a farmer in suburban Shanghai, where they had I This research was supported by Japanese Ministry of Education Grant (C) 59570l60and by the Foundation for the Promotion ofCancer Research,Japanese been kept outdoors. They were Sacrificed, and their sera and tissues Ministry ofHealth and Welfare. were used as described above. 2 To whom requests for reprints should be addressed, at Department of Pathology, Nihon University, School of Medicine, 30-1 Oyaguchi-kamimachi, DHBV DNA Assay Itabashi-ku, Tokyo 173, Japan. 3 The abbreviations used are: DHBV, duck hepatitis B virus SSC, standard saline citrate; GOT, glutamic oxaloacetic transaminase; GPT, glutamic pyruvic Serum was used for determining DHBV DNA by spot hybridization transaminase;PBS,phosphate-bufferedsaline. assayusing cloued DHBV DNA (donated by Dr. William Mason) with 1319 Downloaded from cancerres.aacrjournals.org on September 27, 2021. © 1988 American Association for Cancer Research. GEOGRAPHICAL PATHOLOGY OF DHBV the modification of Scott et a!. (13). The entire DHBV genome was RESULTS subclonedfrom Charon 27-RI (14), and then a 32P-labeledprobeof DHBV was prepared by nick translation (15) with (a-32PJdCTP(800 DHBV DNA Assay Ci/mmol; Amersham, United Kingdom). Among 19 Chiba ducks inoculated with DHBV, 18 showed A sample of 5 @lofserum was mixed with 5 @tlof2 MNaCI and then DHBV DNA in their sera, and all 10 uninoculated ducks did with 10 ,@lof I M NaOH, followed by application to a nitrocellulose not. One duck appeared to have lost evidence of DHBV DNA, filter previously soaked in 20x SSC (lx SSC = 0.15 M NaCl:0.0l5 M sodium citrate, pH 7.0). The nitrocellulose filter was dried and kept at and it was excluded from the DHBV-positive group. Similarly, 80'C under a vacuum for 2 h, prehybridized at 42'C for 4 h, and then all 15 Shimane ducks that had received DHBV inoculation hybridized at 42'C overnight using 2 x l0@cpmof 32P-labeledDHBV revealed DHBV DNA in their sera, while one duck that was DNA (specific activity, 1 x l0@cpm/@g)in 4 ml for 50% formamide, not inoculated was negative for DHBV DNA. Among 99 5x SSC, 5x Denhardt's solution, and 100 @tg/mlsonicated salmon Shanghai ducks, 72 showed DHBV DNA in their sera. The sperm DNA. The filter was then washed 3 times for 10 mm each in amount of DHBV DNA was quite variable among the ducks, 0.lx SCC-0.2% sodium dodecyl sulfate at 50'C. The dried filter was and it ranged from 5 to more than 500 pg/S @lofserum (data autoradiographedat—70'CusingKodak XAR-5 film. The detailed not shown). There was no significant difference in the amount procedure was described previously (6). The results were expressed of DHBV DNA among the ducks of the three different areas. semiquantitatively by comparing the intensity of the standard signals. All the serum samples obtained were subjected to DHBV DNA mess A Southern blot analysis of the livers of 4 ducks (including 3 urement. from Chiba with hyperplastic focal changes described later), 6 Liver tissues were used for a Southern blot hybridization analysis from Shimane, and 6 from Shanghai showed almost the same (16) of DHBV DNA. Total cellular DNA was extracted by treating the pattern of DHBV DNA (data not shown). There were bands tissue overnight with a 20-fold volume of lysis
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