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mammalian hepatitis b viruses and primary liver cancer.hepatitis b virus is a major etiologic agent in the development of human hepatocellular carcinoma, but the precise role of the virus in the tumorigenic process is still unclear. recent studies of naturally occurring animal models, such as woodchucks and squirrels infected with hepatitis b-like viruses (hepadnaviruses) have revealed different oncogenic strategies and outlined the predominant role of myc genes in rodent hepatomas. higher oncogenicity of woodchuck hepatitis virus has been correlate ...19921335794
frequent amplification of c-myc in ground squirrel liver tumors associated with past or ongoing infection with a hepadnavirus.persistent infection with hepatitis b virus (hbv) is a major cause of hepatocellular carcinoma (hcc) in humans. hcc has also been observed in animals chronically infected with two other hepadnaviruses: ground squirrel hepatitis virus (gshv) and woodchuck hepatitis virus (whv). a distinctive feature of whv is the early onset of woodchuck tumors, which may be correlated with a direct role of the virus as an insertional mutagen of myc genes: c-myc, n-myc, and predominantly the woodchuck n-myc2 retr ...19921570307
regulation of polyadenylation in hepatitis b viruses: stimulation by the upstream activating signal ps1 is orientation-dependent, distance-independent, and additive.hepatitis b viruses replicate by reverse transcription of a genomic rna which harbors terminal redundancies. the synthesis of this rna requires that transcription proceed twice through the polyadenylation (pa) site which, in mammalian strains, is flanked by the variant hexanucleotide uauaaa and a t-rich downstream domain. these core elements are by themselves virtually defective in 3' end processing and require multiple upstream accessory elements which regulate pa site use. in ground squirrel h ...19911754382
woodchuck hepatitis virus is a more efficient oncogenic agent than ground squirrel hepatitis virus in a common host.chronic infection with hepatitis b viruses (hepadnaviruses) is a major cause of hepatocellular carcinoma (hcc), but the incubation time varies from 1 to 2 years to several decades in different host species infected with indigenous viruses. to discern the influence of viral and host factors on the kinetics of induction of hcc, we exploited the recent observation that ground squirrel hepatitis virus (gshv) is infectious in woodchucks (c. seeger, p. l. marion, d. ganem, and h. e. varmus, j. virol. ...19912002538
hepadnaviruses, their infections and hepatocellular carcinoma.ten years ago hepatitis b virus (hbv) was thought to be a unique virus, not included in any known family of viruses. following the discovery of a number of hbv-like viruses that infect birds and mammals, the existence of a new family known as hepadnaviridae has been confirmed. hepadnaviruses are small hepatotropic viruses that have a characteristic partially double stranded genome, exhibit a narrow host range and replicate by reverse transcription. the family currently comprises six viruses of w ...19902178194
the hepatitis b virus x-c fusion protein is unlikely to be produced by the mechanism of ribosomal frameshifting.a novel hepatitis b viral (hbv) protein of 35-40 kda, characterized by antibodies and proposed as an x-c fusion protein, was previously described in core particles isolated from hbv-, whv-, and gshv-infected livers. the x and c genes are two adjacent genes in all mammalian hepadnaviruses but are not contiguous in whv and gshv. after examination of the x and prec/c junction sequences of 10 hbv, 4 whv, and 1 gshv, we found that the orf of prec can be extended 7 more sense codons upstream so that x ...19902219709
mapping the major transcripts of ground squirrel hepatitis virus: the presumptive template for reverse transcriptase is terminally redundant.the ground squirrel hepatitis virus (gshv) belongs to a recently defined class of viruses with open circular dna genomes that encode proteins in extensively overlapping reading frames and appear to replicate via rna intermediates. we have determined the primary structure of the major gshv transcripts in the livers of infected ground squirrels. both major classes of transcripts, 2.3 kb and 3.5 kb, are plus-stranded, unspliced, polyadenylated at a common position, and display heterogeneous 5' ends ...19852410139
in vitro infection of woodchuck hepatocytes with woodchuck hepatitis virus and ground squirrel hepatitis virus.primary cultures of woodchuck hepatocytes were demonstrated to be susceptible to in vitro infection by both woodchuck hepatitis virus and ground squirrel hepatitis virus, as evidenced by the appearance of dna species characteristic of hepadnavirus replication. initiation of infection by woodchuck hepatitis virus was blocked by the presence of suramin, polybrene, or dideoxycytidine. viral ccc dna, the putative template for viral rna transcription, was detected at 2 days postinfection. accumulatio ...19892549713
hepadnaviruses and hepatocellular carcinoma (hcc).members of the hepadnavirus family share properties of virion structure, genome structure and replication, epidemiologic behavior, and pathogenic effects. persistent infections with hepatitis b virus (hbv) in man, woodchuck hepatitis virus (whv) in marmota monax, ground squirrel hepatitis virus (gshv) in spermophilus beecheyi, and duck hepatitis b virus (dhbv) in domestic ducks of china are associated with development of hepatocellular carcinoma (hcc). epidemiological evidence implicating hepadn ...19892559799
host-independent evolution and a genetic classification of the hepadnavirus family based on nucleotide sequences.an analysis of molecular phylogeny was undertaken to examine whether the evolution of the hepadnavirus family is host-dependent. using the nucleotide sequences of 18 strains, we constructed phylogenetic trees. the trees obtained show that all 12 strains of hepatitis b virus can be classified into four subgroups that are not compatible with conventional subtypes. we estimated the rate of synonymous (silent) substitution for hepatitis b virus to be 4.57 x 10(-5) per site per year. applying this ra ...19892780562
transcriptional activation of homologous and heterologous genes by the hepatitis b virus x gene product in cells permissive for viral replication.the potential of the hepadnavirus x gene product to activate gene expression in trans was tested through a series of cotransfections of x expression vectors with a variety of potential targets for transactivation. the x gene products from human hepatitis b virus (hbv), woodchuck hepatitis virus, and ground squirrel hepatitis virus are all equally active in augmenting the expression of a wide array of target promoters in both permissive and nonpermissive cells. using the hbv genome itself as the ...19892788226
hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus.although persistent infection with hepatitis b virus and woodchuck hepatitis virus has been associated with development of hepatocellular carcinoma in the host, little has been known of such an association with ground squirrel hepatitis virus (gshv), which is closely related to the woodchuck virus. colonies of gshv-infected and -uninfected beechey ground squirrels were observed for tumors for a period of 5 years. tumors developed in seven squirrels after a minimum of 2.4 years of observation per ...19863012572
in vitro recombinants of ground squirrel and woodchuck hepatitis viral dnas produce infectious virus in squirrels.hepatitis b viruses of humans, woodchucks, ground squirrels, and ducks are similar biochemically but differ with respect to host range and pathogenicity. to pursue the genetic basis of these properties in the absence of a cell culture system for virus growth, we exploited the demonstrated infectivity of cloned hepatitis b virus dna in whole animals. we constructed several recombinant molecules in vitro between cloned infectious genomes of woodchuck hepatitis virus (whv) and ground squirrel hepat ...19873041044
dna-binding activity of hepatitis b e antigen polypeptide lacking the protaminelike sequence of nucleocapsid protein of human hepatitis b virus.the characteristics of binding of hepatitis b core antigen (hbcag) and hepatitis b e antigen (hbeag) polypeptides to hepatitis b virus (hbv) dna were analyzed. hbcag polypeptide from recombinant hbv core particles and hbeag polypeptide from partially purified serum hbeag were prepared and verified to have molecular weights of 21,500 (p21.5) and of 17,000 (p17) and 18,000 (p18), respectively, by immunoblot analysis. by reaction of these proteins on a nitrocellulose membrane with cloned 32p-hbv dn ...19883404582
experimental transmission of duck hepatitis b virus to pekin ducks and to domestic geese.we investigated experimental transmission of duck hepatitis b virus to its original host, the domestic pekin duck, and to three other avian species. intramuscular injection of a standard inoculum of duck hepatitis b virus into 2- to 5-day-old pekin ducklings hatched from a duck hepatitis b virus-free flock resulted in viremia in 100% of 107 animals, indicating that duck hepatitis b virus infection of young progeny of a defined duck hepatitis b virus-free flock occurs reproducibly. when the same ...19873610050
hepadnaviruses and retroviruses share genome homology and features of replication.the hepadnavirus family includes hepatitis b virus (hbv), woodchuck hepatitis virus (whv), ground squirrel hepatitis virus (gshv) and duck hepatitis b virus (dhbv). these viruses share unique ultrastructural, molecular and biological features. hbv has great medical importance in many parts of the world. more important numerically than acute hepatitis b in high prevalence geographic regions is the liver disease associated with chronic infection. there appear to be more than 200 million chronicall ...19873804216
nucleotide sequence of a cloned woodchuck hepatitis virus genome: evolutional relationship between hepadnaviruses.we have determined the complete nucleotide sequence of a cloned dna of woodchuck hepatitis virus (whv), the most oncogenic virus among hepadnaviruses. the genome, designated whv2, is 3,320 base pairs long and contains four major open reading frames (orfs) coded on the same strand of nucleotide sequence as in the human hepatitis b virus (hbv) genome. comparison of the nucleotide sequence and amino acid sequences deduced from it among the genomes of various hepadnaviruses demonstrates that each pr ...19853855246
identification and localization of pre-s-encoded polypeptides from woodchuck and ground squirrel hepatitis viruses.a segment from the pre-s region of the woodchuck hepatitis virus (whv) was inserted into an open reading frame vector allowing for the expression in escherichia coli of viral determinants as part of a fusion protein. the bacterially synthesized fusion molecule contained eight amino acids from beta-galactosidase (beta-gal) at the n terminus, followed by 89 pre-s-encoded amino acids and 219 amino acids of chloramphenicol acetyltransferase (cat) at the c terminus (beta-gal:pre-s:cat). this tribrid ...19863941437
nucleotide sequence of an infectious molecularly cloned genome of ground squirrel hepatitis virus.we have determined the complete nucleotide sequence of an infectious cloned genome of ground squirrel hepatitis virus (gshv), a nonpathogenic member of the hepadnavirus group. the genome is 3,311 base pairs long and contains the major open reading frames described for the related human and woodchuck hepatitis b viruses (hbv and whv, respectively). these reading frames include genes for the major structural proteins (the surface and core antigens), unassigned open reading frames (a and b), the lo ...19846086950
antigenic and structural relationships of the surface antigens of hepatitis b virus, ground squirrel hepatitis virus, and woodchuck hepatitis virus.the surface antigens of human hepatitis b (hbsag), ground squirrel hepatitis (gshsag), and woodchuck hepatitis (whsag) viruses were compared serologically, and their major polypeptides were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping. results showed that both gshsag and whsag are antigenically cross-reactive, that their major pairs of polypeptides have identical mobilities on sodium dodecyl sulfate gels, and that the major polypeptides of gsh ...19816168776
surface antigenic determinants of mammalian "hepadnaviruses" defined by group- and class-specific monoclonal antibodies.the hepatitis b-like viruses (human hepatitis b virus, woodchuck hepatitis virus, ground squirrel hepatitis virus, and duck hepatitis b virus) are hepatotropic dna viruses which have been referred to collectively as "hepadnaviruses." using a murine monoclonal antibody (101-2) to the surface antigen of woodchuck hepatitis virus, we have shown that the surface antigens of mammalian hepadnaviruses (hbsag, whsag, and gshsag) are antigenically related via a common determinant (hv/101). furthermore, a ...19826177867
ground squirrel hepatitis virus dna: molecular cloning and comparison with hepatitis b virus dna.ground squirrel hepatitis virus (gshv) shares many ultrastructural antigenic, molecular, and biological features with hepatitis b virus (hbv) of humans, indicating that they are members of the same virus group. both viruses contain small circular dna molecules which are partially single stranded. here, we ligated an endonuclease ecori digest of gshv dna with ecori-cleaved plasmid vector pbr322 and cloned recombinant plasmids in escherichia coli c600. two cloned recombinants were characterized. o ...19816264112
virion dna of ground squirrel hepatitis virus: structural analysis and molecular cloning.the structure of the encapsidated dna genome of ground squirrel hepatitis virus (gshv) has been examined by restriction endonuclease cleavage, nucleic acid hybridization, and molecular cloning. gshv virion dna is a relaxed circular molecule of approximately 3,200 bases in length; most molecules harbor an extensive single-stranded region which is largely confined to one-half of the genome. the full-length viral dna strand is covalently bound to protein. the single-stranded region can be repaired ...19826292498
hepatitis b viral dna-rna hybrid molecules in particles from infected liver are converted to viral dna molecules during an endogenous dna polymerase reaction.particles purified from the liver of hepatitis b virus-infected patients were previously shown by us to incorporate 32p-deoxynucleotides into viral dna and dna-rna hybrid molecules when incubated in a dna polymerase reaction mixture. in this investigation, similar particles from duck and ground squirrel livers infected with viruses closely related to hbv were also shown to incorporate 32p-deoxynucleotides into viral-specific dna and dna-rna hybrid molecules when incubated in vitro in a dna polym ...19846495660
the nature of polypeptides larger in size than the major surface antigen components of hepatitis b and like viruses in ground squirrels, woodchucks, and ducks.the relationships of various polypeptides associated with hepatitis b surface antigen (hbsag), ground squirrel hepatitis surface antigen (gshsag), woodchuck hepatitis surface antigen (whsag), and duck hepatitis b surface antigen (dhbsag) were studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (sds-page) and tryptic peptide mapping. analysis of independent antigen isolates by sds-page resulted in bands consistently observed at 24,000, 28,000, 32,000, 43,000, and 50,000 da with h ...19836636542
ground squirrel hepatitis virus infection. 19836862363
nonoverlapping antigenic sites of woodchuck hepatitis virus surface antigen and their cross-reactivity with ground squirrel hepatitis virus and hepatitis b virus surface antigens.five nonoverlapping antigenic sites (sites i through v) of woodchuck hepatitis virus surface antigen were identified with competitive binding assays involving monoclonal antibodies. site i contributed to cross-reactions among surface antigens of hepatitis b-like viruses infecting woodchucks, ground squirrels, and humans. at least three distinct sites (sites i, ii, and iii) are responsible for cross-reactions between woodchuck and ground squirrel hepatitis virus surface antigens. sites iv and v o ...19836864882
a virus in beechey ground squirrels that is related to hepatitis b virus of humans.a virus given the name ground squirrel hepatitis virus (or gshv), with many of the unique characteristics of human hepatitis b virus (hbv), has been found in beechey ground squirrels in northern california. common features include virus morphology, viral dna size and structure, a virion dna polymerase that repairs a single-stranded region in the viral dna, crossreacting viral antigens, and persistent infection with viral antigen continuously in the blood. although similar, gshv and hbv are not i ...19806930677
genetic variation among hepatitis b and related viruses.hepatitis b virus (hbv) of man has several characteristics that distinguish it from viruses of other groups. these include its ultrastructure, viral dna size and structure, a virion dna polymerase which repairs a single-stranded region in the viral dna, liver tropism, character of persistent infection, and association with hepatitis and hepatocellular carcinoma. recently three other viruses have been found in other animal species that appear to share these characteristics although the viruses ar ...19807013620
core particles of hepatitis b virus and ground squirrel hepatitis virus. i. relationship between hepatitis b core antigen- and ground squirrel hepatitis core antigen-associated polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping.the relationships among the core antigen polypeptides of hepatitis b virus (hbv) and ground squirrel hepatitis virus (gshv) were studied using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and tryptic peptide mapping. the major core antigen polypeptides of liver-derived hbv (p22) and gshv (p20.5) shared 56% of the spots in their peptide maps. comparison of hepatitis b core antigen (hbcag) p19 or ground squirrel hepatitis core antigen (gshcag) p16.5 with their respective major polypep ...19827109037
core particles of hepatitis b virus and ground squirrel hepatitis virus. ii. characterization of the protein kinase reaction associated with ground squirrel hepatitis virus and hepatitis b virus.the recently described protein kinase activity in hepatitis b virus core antigen particles (albin and robinson, j. virol. 34:297-302, 1980) has been demonstrated here in the liver-derived core particles of ground squirrel hepatitis virus. both protein kinase activities were initially associated with dna polymerase-positive heavy core particles in cscl density equilibrium gradients and shifted to polymerase-negative cores during the course of purification. the major core-associated polypeptide of ...19827109041
biological characterization of acute infection with ground squirrel hepatitis virus.ground squirrel hepatitis virus (gshv) is a small dna virus, structurally and antigenically related to the human hepatitis b virus, which occurs naturally among certain wild populations of ground squirrels (p. l. marion et al., proc. natl. acad. sci. u.s.a. 77:2941-2945, 1980). serum from naturally infected animals was used to transmit gshv in the laboratory by parenteral inoculation of susceptible squirrels. sixty percent of recipient animals developed viral surface antigenemia after a latent p ...19827143570
structural relationships between the surface antigens of ground squirrel hepatitis virus and human hepatitis b virus.several physical, chemical, and serological properties of surface antigen particles from ground squirrel hepatitis virus (gshsag) and human hepatitis b virus (hbsag) were compared. gshsag and hbsag particles were purified from positive sera by gel chromatography and isopycnic centrifugation. both antigens consisted mainly of spherical particles with an average diameter of approximately 20 nm and a buoyant density in cscl of approximately 1.19 g/ml. their uv absorption spectra indicated the prese ...19807463556
virus of pekin ducks with structural and biological relatedness to human hepatitis b virus.a virus found in the sera of pekin ducks appears to be a new member of the human hepatitis b-like family of viruses. this virus had a diameter of 40 nm and an appearance in the electron microscope similar to that of human hepatitis b virus. the dna genome of the virus was circular and partially single stranded, and an endogenous dna polymerase associated with the virus was capable of converting the genome to a double-stranded circle with a size of ca. 3,000 base pairs. an analysis for viral dna ...19807463557
phenotypic mixing between different hepadnavirus nucleocapsid proteins reveals c protein dimerization to be cis preferential.hepadnaviruses encode a single core (c) protein which assembles into a nucleocapsid containing the polymerase (p) protein and pregenomic rna during viral replication in hepatocytes. we examined the ability of heterologous hepadnavirus c proteins to cross-oligomerize. using a two-hybrid assay in hepg2 cells, we observed cross-oligomerization among the core proteins from hepatitis b virus (hbv), woodchuck hepatitis virus, and ground squirrel hepatitis virus. when expressed in xenopus oocytes, in w ...19947518533
state of the p53 gene in hepatocellular carcinomas of ground squirrels and woodchucks with past and ongoing infection with hepadnaviruses.infection with hepadnaviruses and exposure to dietary aflatoxin are considered major risk factors in the development of hepatocellular carcinoma (hcc) both in humans and in animals. recently, a broad range of mutations in the p53 tumor suppressor gene has been reported in human hccs, predominantly from hepatitis b virus carriers in areas with either high or low levels of exposure to dietary aflatoxin. to determine whether p53 mutations are common to hccs of hosts infected with related hepadnavir ...19947923176
analysis of integrated ground squirrel hepatitis virus and flanking host dna in two hepatocellular carcinomas.we cloned the integrated ground squirrel hepatitis b virus (gshv) sequences from two hepatomas showing a single viral insertion. the gshv inserts shared structural features with integrated dnas of other hepadnaviruses. insertional activation of a cellular gene appears unlikely: the integrated gshv sequences lacked the known viral enhancers and were not expressed in the tumors, and we found no evidence for the presence of a gene at the integration site. our results, together with those earlier st ...19948035528
duck hepatitis b virus infection, aflatoxin b1 and liver cancer in ducks.the association between chronic infection by hepadnaviruses isolated from human (hbv), woodchuck (whv), ground squirrel (gshv) and development of hepatocellular carcinoma (hcc) in their respective hosts is well established (reviewed in [11, 15, 17]). by contrast, the association of duck hepatitis b virus (dhbv) infection with hcc is less documented. pekin ducks congenitally infected with dhbv and followed for several years throughout the world do not develop liver tumors: hcc has been found only ...19938260880
differential activation of myc gene family members in hepatic carcinogenesis by closely related hepatitis b viruses.woodchucks infected with woodchuck hepatitis virus (whv) and ground squirrels infected with ground squirrel hepatitis virus (gshv) both develop hepatocellular carcinoma (hcc), but whv-associated tumors arise more frequently and much earlier in life. these differences are preserved when the oncogenic potentials of the two viruses are examined in the same host (woodchucks). we examined rna and genomic dna from tumors arising from whv- and gshv-infected woodchucks to determine whether these viruses ...19938380230
activation of n-myc2 gene expression by cis-acting elements of oncogenic hepadnaviral genomes: key role of enhancer ii.woodchuck hepatitis virus (whv) is strongly oncogenic in its native host, producing hepatocellular carcinomas in the majority of chronically infected animals. an important step in this oncogenic process is the activation of n-myc transcription in the liver as a result of integration of viral sequences in cis to the n-myc2 locus. we have examined the viral sequences involved in the up-regulation of n-myc2 using transient transfection assays of permissive hepg2 cells in culture. whv sequences corr ...19968599232
sequences regulating poly(a) site selection within the adenovirus major late transcription unit influence the interaction of constitutive processing factors with the pre-mrna.the adenovirus major late transcription unit (mltu) encodes five families of mrnas, l1 to l5, each distinguished by a unique poly(a) site. use of the promoter-proximal l1 poly(a) site predominates during early infection, whereas poly(a) site choice shifts to the promoter-distal sites during late infection. a mini-mltu containing only the l1 and l3 poly(a) sites has been shown to reproduce this processing switch. in vivo analysis has revealed that sequences extending 5' and 3' of the l1 core poly ...19968627700
a new hepadnavirus endemic in arctic ground squirrels in alaska.we present evidence for a novel member of the hepadnavirus family that is endemic in wild arctic ground squirrels (spermophylus parryi kennicotti) in alaska. this virus, designated arctic squirrel hepatitis virus (ashv), was initially detected in the livers of animals bearing large hepatic nodules by nucleic acid hybridization with hepadnavirus probes and in plasma by cross-reactivity with antibodies to hepadnavirus surface and core antigens. the complete nucleotide sequence of the 3,302-bp-long ...19968676441
absence of mutations in the p53 tumor suppressor gene in woodchuck hepatocellular carcinomas associated with hepadnavirus infection and intake of aflatoxin b1.infection with hepadnaviruses and exposure to aflatoxin b1 (afb1) are considered major risk factors in the development of hepatocellular carcinoma (hcc) in humans and in animals. a high rate of mutations in the p53 tumor suppressor gene in hepatocellular carcinomas of predominantly hepatitis b virus (hbv) carrier patients has been recently related to dietary aflatoxin. another member of the hepadnavirus family, the woodchuck hepatitis virus (whv), infects woodchucks in a manner similar to that o ...19969006107
functional analysis of ground squirrel hepatitis virus enhancer ii.we have characterized a major regulatory element of ground squirrel hepatitis virus (gshv) located within a 90-nucleotide fragment of the core promoter upstream sequences and have compared its organization to that of woodchuck hepatitis virus (whv) enhancer ii (we2). the gshv element (ge2) stimulates transcription from the viral core promoter and heterologous promoters in an orientation-independent manner but displays a lower level of activity than we2 in transient transfection assays in human h ...19989445066
origins and evolution of hepatitis b virus and hepatitis d virus.members of the family hepadnaviridae fall into two subgroups: mammalian and avian. the detection of endogenous avian hepadnavirus dna integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. the nonprimate mammalian members of the hepadnaviridae include the woodchuck hepatitis virus (whv), the ground squirrel hepatitis virus, and arctic squirrel he ...201626729756
possible origins and evolution of the hepatitis b virus (hbv).all members of the family hepadnaviridae are primarily viruses which contain double-stranded dna genomes that are replicated via reverse transcription of a pregenomic rna template. there are two subgroups within this family: mammalian and avian. the avian member's include the duck hepatitis b virus (dhbv), heron hepatitis b virus, ross goose hepatitis b virus, stork hepatitis b virus and the recently identified parrot hepatitis b virus. more recently, the detection of endogenous avian hepadnavir ...201324013024
potential mechanisms of hepatitis b virus induced liver injury.chronic active hepatitis (cah) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. the histological end points of cah are chronic inflammation, fibrosis and cirrhosis which are coupled with increased dna synthesis in cirrhotic vs healthy normal livers. the potential mechanism involved in cah includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). the severity ...201425253946
harderian gland neoplasms in captive, wild-caught beechey ground squirrels (spermophilus beecheyi).harderian gland neoplasms were identified in 18 aged, adult beechey ground squirrels (spermophilus beecheyi) from the records of 167 wild-caught captive animals that were necropsied. all but one animal had tumors that were classified as carcinomas, with infiltrative growth and frequent metastases. this is the first detailed report of harderian gland neoplasia in wild sciuridae, although this neoplasm has been described in other rodent species. clinically, affected ground squirrels typically were ...200818487500
non-neoplastic liver disease associated with chronic ground squirrel hepatitis virus infection.we examined 95 ground squirrels to compare the histological appearance of liver sections from animals that were chronically infected with ground squirrel hepatitis virus (gshv) (n = 29), uninfected (n = 42), or had recovered from infection (n = 24). we studied the effects of long-term infection because these animals had been infected with gshv for up to 10 years. chronic infection generally produced a mild, persistent hepatitis characterized by light lymphocytic and plasmacytic portal infiltrate ...19968675146
upstream sequences and cap proximity in the regulation of polyadenylation in ground squirrel hepatitis virus.the polyadenylation signal of mammalian hepadnaviruses is unusual in that its hexanucleotide element is the variant uauaaa rather than aauaaa. this signal functions inefficiently and must be augmented by multiple activator elements located in the upstream 400 nucleotides (nt) to promote efficient processing. here we characterize one of these upstream elements, termed ps2, in the ground squirrel hepatitis virus. ps2 is located within the 107 nt 5' to the uauaaa and raises the efficiency of polyad ...19921279209
hepatocellular carcinoma in richardson's ground squirrels (spermophilus richardsonii): evidence for association with hepatitis b-like virus infection.during studies of seasonal obesity, a high frequency of hepatic neoplasms was observed in richardson's ground squirrels. of 12 richardson's ground squirrels examined thoroughly, 7 had mild or moderate degrees of chronic portal hepatitis and 6 (50%) had hepatocellular carcinoma. serological tests for hepadnavirus surface antigen, anti-core antibody and virion dna that recognize the ground squirrel hepatitis virus of california ground squirrels (spermophilus beecheyi) were uniformly negative. sout ...19911646762
5'-terminal sequences influence the segregation of ground squirrel hepatitis virus rnas into polyribosomes and viral core particles.to determine which of the major ground squirrel hepatitis virus rnas serve as mrnas and which serve as templates for reverse transcription of the genome, we analyzed the subcellular distribution of these rnas in livers of infected ground squirrels. both major classes of viral rna, the 2.3- and 3.5-kilobase (kb) classes, are unspliced, are polyadenylated at a common position, and display heterogeneous 5' ends that can encode proteins with different amino termini (g.h. enders, d. ganem, and h. var ...19872431165
ground squirrel hepatitis virus (gshv) infection and hepatocellular carcinoma in the canadian richardson ground squirrel (spermophilus richardsonii).sera and livers from 40 richardson ground squirrels were examined for evidence of ground squirrel hepatitis virus (gshv) infection and hepatocellular carcinoma. twenty-five sera were obtained from fully grown adult ground squirrels and 15 from young ground squirrels estimated to be between 6-8 weeks of age. all animals had been caught in the wild and had spent less than 1 month in captivity. sixteen sera (40%) had at least one serologic marker of gshv (2 with gshv surface antigen, 3 gshv core an ...19863033421
antibodies to pre-s and x determinants arise during natural infection with ground squirrel hepatitis virus.the dna sequence of the ground squirrel hepatitis virus (gshv) genome predicts the existence of several proteins in addition to the major surface (s) and core antigens. these include the pre-s1 and pre-s2 proteins, initiated at sites within the open reading frame preceding and continuous with the coding region for the s gene product, and the x protein, the putative product of an independent reading frame. using an antibody directed against a peptide predicted by codons 130 to 143 of the pre-s1 r ...19862427746
transmission of ground squirrel hepatitis virus to homologous and heterologous hosts.the infectivity and host range of ground squirrel hepatitis virus (gshv) have been further examined by animal inoculation experiments. although carrier squirrel sera usually harbor 10(9) to 10(10) virions per ml as determined by physical measurements, titration of one such serum revealed that squirrel infectivity was lost following dilution of the sample over 10(6)-fold. infectivity is markedly reduced by np40 pretreatment of infected serum. gshv infection cannot be readily transmitted to severa ...20063997073
activities of arabinosyladenine monophosphate and 9-(1,3-dihydroxy-2-propoxymethyl)guanine against ground squirrel hepatitis virus in vivo as determined by reduction in serum virion-associated dna polymerase.treatment of chronic ground squirrel hepatitis virus infection with arabinosyladenine monophosphate at 20 mg/kg per day for 3 weeks caused marked decreases in serum virion-associated dna polymerase concentrations in three of five squirrels. statistically significant but less dramatic decreases in enzymatic activity were noted in two of six squirrels treated with 50 mg of 9-(1,3-dihydroxy-2-propoxymethyl)guanine per kg per day. after therapy, dna polymerase activities rose to pretreatment levels.19852580482
the cloned genome of ground squirrel hepatitis virus is infectious in the animal.the lack of an in vitro infectivity assay for hepatitis b viruses has impeded the analysis of their genetic organization. to examine the feasibility of generating mutant and recombinant viruses after manipulation of cloned viral dna in vitro, we have tested the infectivity of the cloned genome of ground squirrel hepatitis virus (gshv) in virus-free beechey ground squirrels. we demonstrate that cloned gshv dna is infectious when injected directly into the liver in the form of trimeric, head-to-ta ...19846091114
closed circular viral dna and asymmetrical heterogeneous forms in livers from animals infected with ground squirrel hepatitis virus.to identify possible intermediates in the replication of ground squirrel hepatitis virus, we characterized the major forms of intracellular virus-specific dna in the livers of infected ground squirrels. a variety of dna species were found: covalently closed circular molecules, relaxed circular molecules, and a heterogeneous collection of molecules that migrated ahead of closed circular dna during agarose gel electrophoresis. the heterogeneous dna was at least partly single stranded, consisted of ...19836887347
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