Studies on transmission of human non‐A, non‐B hepatitis to marmosets

Watanabe, Toshiaki; Katagiri, Jiro; Kojirna, Hideo; Kamimura, Tomoteru; Ichida, Fumihiro; Ashida, Masahiko; Harnada, Chuya; Shibayama, Takao

doi:10.1002/jmv.1890220205

Cited by 10 publications

(7 citation statements)

References 19 publications

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“…Direct and indirect evidence of HEV transmission from wild boars and pigs to humans has been reported in Japan, suggesting that these animals are the main zoonotic reservoirs in this country [8,27]. Chimpanzees, rhesus monkeys, cynomolgus monkeys, and marmosets have been used for experimental infection and to evaluate the efficacy of HEV vaccines, and HEV has been used as a challenge virus, indicating that these monkeys are susceptible to HEV infection [13,22,29,30]. In addition to these animals, anti-HEV IgG antibody has been detected in dogs, cats, cows, goats, sheep, and rodents including rats [4,7,14,19], and anti-HEV IgG antibody and HEV RNA were detected from mongoose and wild deer [9,21,28].…”

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confidence: 99%

Mice are Not Susceptible to Hepatitis E Virus Infection

Suzaki

Ami

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. To determine whether or not mice are susceptible to hepatitis E virus (HEV) infection, C57BL/6 mice were experimentally infected with genotypes 1, 3 and 4 HEV by intravenous injection. Serum and stool samples were collected and used to detect HEV RNA and anti-HEV antibodies by RT-PCR and ELISA. The virus infection was monitored up to two months after inoculation; however, none of the serum or stool samples was positive for virus replication, demonstrating that C57BL/6 mice were not susceptible to HEV. KEY WORDS: C57BL/6, hepatitis E, hepatitis E virus, HEV, mouse.J. Vet. Med. Sci. 70(12): 1359-1362, 2008 Hepatitis E is a serious public health concern in many developing countries, and recognized as sporadic and endemic acute hepatitis in many industrialized countries. Pregnant women have a high risk associated with hepatitis E, with a high mortality rate (up to 20%) [5,25]. The causative agent of hepatitis E is hepatitis E virus (HEV), and this virus transmits primarily via the fecal-oral route through contaminated drinking water [1,6]. HEV is the sole member of the genus Hepevirus in the family Hepeviridae. HEV is a small round non-enveloped virus, 27-34 nm in diameter, containing an RNA genome approximately 7.2 kb in length [2,3]. The RNA consists of a single-strand RNA molecule containing three discontinuous and partially overlapping open reading frames (ORFs). The 3' terminus of the RNA is polyadenylated. HEV isolates were grouped into at least four major genotypes, genotypes 1, 2, 3 and 4 (G1, G2, G3 and G4) on the basis of nucleotide and deduced amino acid sequences [3,6,24]. Because G3 and G4 HEV were isolated from pigs and wild boars in addition to humans, and much direct and indirect evidence has indicated that HEV transmits from pigs or wild boars to humans, hepatitis E is recognized as a zoonotic disease [8,18,23]. Many studies have reported the detection of HEV RNA and the HEV-specific antigen (HEV-Ag) in pig and wild boar stool and serum specimens, and suggested the active circulation of this virus among these animals [18,20,26]. HEV-specific antibodies have been detected in many animals including sheep, cows, dogs, cats, wild rats, wild deer and mongoose, in addition to pigs and wild boars [9,12,14,15,19]. However, it is obscure whether or not HEV substantially replicates in these animals. In this study we infected C57BL/6 mice with G1, G3 and G4 HEV, and monitored the virus growth to determine the susceptibility of mice to HEV infection.G1 HEV strain was derived from stool specimens from a cynomolgus monkey (Macaca fascicularis), born and grown in the Tsukuba Primate Center for Medical Science, National Institute of Infectious Diseases (NIID), which had been experimentally infected with an Indian strain [10]. The G3 HEV strain (DQ079632) was derived from stool specimens collected on a pig farm in Japan. The G4 HEV strain (DQ079628) was from a stool specimen collected from a wild boar caught in Aichi prefecture, Japan. The stool specimens were used to prepare 10% (w/v) suspensions as descr...

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confidence: 99%

Mice are Not Susceptible to Hepatitis E Virus Infection

Suzaki

Ami

et al. 2008

The Journal of Veterinary Medical Science

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“…Efforts to develop small animal infection models have included trying to transmit HCV to tree shrews [175,190], marmosets/tamarins[44,83,169], and other primates[1], but only the chimpanzee model of HCV infection, has proven efficacious[93,178]. The species barriers that prevent HCV infection in non-human hosts are not completely defined, but include blocks in viral entry and non-permissiveness for HCV RNA replication.…”

Section: The Future Of Hcv Antiviral Researchmentioning

confidence: 99%

Hepatitis C virus experimental model systems and antiviral drug research

Uprichard

2010

Virol. Sin.

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An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics. KeywordsHepatitis C virus; Chronic liver disease; Experimental model systems; High throughput screening; Drug targets Hepatitis C virus (HCV), a member of the Flaviviridae family of enveloped positive-strand RNA viruses, is a leading cause of liver disease worldwide. Although HCV infection is usually asymptomatic and 10-30% of infected individuals successfully clear the infection [2,145], 70% of infections persist with the risk of progressive liver complications, such as fibrosis, cirrhosis, steatosis, insulin resistance, and/or hepatocellular carcinoma (HCC) [4,5,43,71,111,133,148,149], which can ultimately necessitate liver transplantation if HCV infection is not successfully treated (Fig. 1).To date, combination pegylated interferon-alpha (pIFN-α) and ribavirin [52] is the licensed standard of care (SOC) treatment for HCV; however, several limitations restrict its use and efficacy. First, because viral, host, and environmental factors significantly affect the success of SOC treatment (reviewed in [162]), numerous contraindications limit the number of patients eligible for therapy. Of those who are treated, sustained virological response (SVR) is only achieved in ~80% of individuals infected with genotypes 2 or 3 and 40%-50% of individuals infected with genotypes 1 or 4 [3]. In addition, therapy itself has a spectrum of toxic side effects and complications, which severely limit patient compliance and thus treatment efficacy [45]. Hence, with an estimated 130 million people worldwide chronically infected [4], and the number of HCV patients needing medical care is expected to increase dramatically over the next decade [171], the development of new more specific HCV antivirals is a healthcare imperative. This review will discuss the experimental models available for HCV antiviral drug research, the most recent advances in HCV antiviral drug development, as well as future research directions focused on developing new HCV-specific therapeutics. HCV EXPERIMENTAL SYSTEMS AVAILABLE FOR ANTIVIRAL DRUG RESEARCHSince it's discovery in 1989 as the causative agent on non-A non-B hepatitis [37], the HCV lifecycle and host-virus interactions that determine infection outcome have been difficult to study because experimental HCV cell culture infection systems and suitable small animal models have not been readily available. Consequently, the development of preventive vaccines and anti-HCV therapeutics has been severely hampered. Notably however...

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“…Efforts to develop small animal HCV infection models have included the attempts to transmit HCV to tree shrews,184,185 marmosets/tamarins,186–188 and other primates189 however, only the chimpanzee has proven to be a reliable HCV animal model. Although xenorepopulation approaches in which mice are repopulated with human hepatocytes have proven to be acceptable for studying HCV infection in vivo, serious technical challenges, such as hepatocyte availability, surgical technical expertise, variability in the degree of repopulation among mice, and the fragile nature of the repopulated mice themselves, all limit the widespread use of this humanized mouse model 190–192.…”

Section: Future Research Challengesmentioning

confidence: 99%

Potential treatment options and future research to increase hepatitis C virus treatment response rate

TenCate

Sáinz²,

Cotler³

et al. 2010

HMER

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Hepatitis C virus (HCV) is a liver-tropic blood-borne pathogen that affects more than 170 million people worldwide. Although acute infections are usually asymptomatic, up to 90% of HCV infections persist with the possibility of long-term consequences such as liver fibrosis, cirrhosis, steatosis, insulin resistance, or hepatocellular carcinoma. As such, HCV-associated liver disease is a major public health concern. Although the currently available standard of care therapy of pegylated interferon α plus ribavirin successfully treats infection in a subset of patients, the development of more effective, less toxic HCV antivirals is a health care imperative. This review not only discusses the limitations of the current HCV standard of care but also evaluates upcoming HCV treatment options and how current research elucidating the viral life cycle is facilitating the development of HCV-specific therapeutics that promise to greatly improve treatment response rates both before and after liver transplantation.

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Studies on transmission of human non‐A, non‐B hepatitis to marmosets

Cited by 10 publications

References 19 publications

Mice are Not Susceptible to Hepatitis E Virus Infection

Mice are Not Susceptible to Hepatitis E Virus Infection

Hepatitis C virus experimental model systems and antiviral drug research

Potential treatment options and future research to increase hepatitis C virus treatment response rate

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