Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm viruslike particles.

Bradley, Daniel W.; Krawczynski, Krzysztof; Cook, E. H.; McCaustland, Karen A.; Humphrey, Charles D.; Spelbring, John; Myint, H.; Maynard, James E.

doi:10.1073/pnas.84.17.6277

Cited by 192 publications

(113 citation statements)

References 12 publications

(12 reference statements)

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“…This higher efficiency is needed when one needs to be certain that HEV, when present, causes infection. However, the natural route for HEV-transmission is most likely faecal-oral [6,31]. The natural route of transmission is required to study transmission dynamics and dynamics of HEV infection in individual animals.…”

Section: Introductionmentioning

confidence: 99%

Estimation of hepatitis E virus transmission among pigs due to contact-exposure

et al. 2008

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-Locally acquired hepatitis E in humans from industrialized countries has been repeatedly suggested to originate from pigs. Pigs may serve as a reservoir of hepatitis E virus (HEV) for humans when a typical infected pig causes on average more than one newly infected pig, a property that is expressed by the basic reproduction ratio R 0 . In this study, R 0 for HEV transmission among pigs was estimated from chains of one-to-one transmission experiments in two blocks of five chains each. Per chain, susceptible first-generation contact pigs were contact-exposed to intravenously inoculated pigs, subsequently susceptible second-generation contact pigs were contact-exposed to infected first-generation contact pigs, and lastly, susceptible third-generation contact pigs were contact-exposed to infected second-generation contact pigs. Thus, in the second and third link of the chain, HEV-transmission due to contact with a contact-infected pig was observed. Transmission of HEV was monitored by reverse transcriptase polymerase chain reaction (RT-PCR) on individual faecal samples taken every two/three days. For susceptible pigs, the average period between exposure to an infectious pig and HEV excretion was six days (standard deviation: 4). The length of HEV-excretion (i.e. infectious period) was estimated at 49 days (95% confidence interval (CI): 17-141) for block 1 and 13 days (95% CI: 11-17) for block 2. The R 0 for contact-exposure was estimated to be , showing the potential of HEV to cause epidemics in populations of pigs. hepatitis E virus / transmission / contact-exposure / reproduction ratio / pigs

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Section: Introductionmentioning

confidence: 99%

Estimation of hepatitis E virus transmission among pigs due to contact-exposure

et al. 2008

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“…Functional analysis of HEV proteins and nucleotide sequences involved in viral replication has been a difficult task, since an efficient cell culture system for HEV is not yet available. Therefore, most studies of HEV replication to date have been performed by transfection or infection of animals (3,8,23,24) or by overexpression of recombinant proteins in vitro (1,18,38,39,44). Agrawal et al reported that the 3Ј noncoding region (NCR) and an adjacent region of the positive strand of genotype 1 strains of HEV form putative stem-loop structures that affect the binding of recombinant viral RdRp in an in vitro assay (1).…”

mentioning

confidence: 99%

In Vitro and In Vivo Mutational Analysis of the 3′-Terminal Regions of Hepatitis E Virus Genomes and Replicons

Graff

Nguyen

Kasorndorkbua

et al. 2005

J Virol

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Hepatitis E virus (HEV) replication is not well understood, mainly because the virus does not infect cultured cells efficiently. However, Huh-7 cells transfected with full-length genomes produce open reading frame 2 protein, indicative of genome replication (6). To investigate the role of 3-terminal sequences in RNA replication, we constructed chimeric full-length genomes with divergent 3-terminal sequences of genotypes 2 and 3 replacing that of genotype 1 and transfected them into Huh-7 cells. The production of viral proteins by these full-length chimeras was indistinguishable from that of the wild type, suggesting that replication was not impaired. In order to better quantify HEV replication in cell culture, we constructed an HEV replicon with a reporter (luciferase). Luciferase production was cap dependent and RNA-dependent RNA polymerase dependent and increased following transfection of Huh-7 cells. Replicons harboring the 3-terminal intergenotypic chimera sequences were also assayed for luciferase production. In spite of the large sequence differences among the 3 termini of the viruses, replication of the chimeric replicons was surprisingly similar to that of the parental replicon. However, a single unique nucleotide change within a predicted stem structure at the 3 terminus substantially reduced the efficiency of replication: RNA replication was partially restored by a covariant mutation. Similar patterns of replication were obtained when full-length genomes were inoculated into rhesus macaques, suggesting that the in vitro system could be used to predict the effect of 3-terminal mutations in vivo. Incorporation of the 3-terminal sequences of the swine strain of HEV into the genotype 1 human strain did not enable the human strain to infect swine.Hepatitis E virus (HEV) is a major cause of enterically transmitted hepatitis, especially in Asia and Africa. Serological prevalence data suggest that HEV might be endemic in industrialized countries as well, although it rarely causes disease in these countries (reviewed in references 7, 19, and 29). Antibodies to HEV (anti-HEV) have also been detected in a wide variety of animals, and HEV has been found in swine (2, 10, 12, 25, 33), deer (35), and chickens (11, 14); these findings raise the possibility that HEV may be a zoonosis (22). HEV strains infecting mammals differ at the nucleotide level by as much as 27%, whereas the avian strain differs from the mammalian strains by up to 50%. The mammalian HEV strains have been classified into four genotypes based on sequence variations (31), but they appear to comprise a single serotype (29,45).HEV differs enough from other viruses that it was recently classified as the sole member of the new genus Hepevirus (5). HEV is nonenveloped and contains a single-stranded RNA genome of positive sense that is capped and polyadenylated. The 7.2-kb genome contains three partially overlapping open reading frames (ORFs). ORF1 encodes a nonstructural polyprotein which provides guanylyl-methyltransferase and RNA-dependent RNA polymera...

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“…17 IEM studies on agglutination of VLPs in stools from HEVinfected individuals showed that diminishing IgG reactivity or seroconversion occurred when acute and serial convalescent phase sera from humans or monkeys were tested. 18 The results of these studies suggest that IgG anti-HEV could be a marker of acute infection. The persistence of IgG anti-HEV for one to four years has been demonstrated in some isolated cases.…”

Section: Long-term Antibody Statusmentioning

confidence: 76%