&lt;i&gt;Tupaia Belangeri&lt;/i&gt; as an Experimental Animal Model for Viral Infection

Tsukiyama-Kohara, Kyoko; Kohara, Michinori

doi:10.1538/expanim.14-0007

Cited by 31 publications

(19 citation statements)

References 37 publications

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“…Specifically for HBV, owing to the lack of robust cell culture and mouse models historically and due to the high cost of chimpanzees, several models have been developed and have provided useful insights into the virus life cycle. Because of the known genetic similarity to primates, the tree shrew ( Tupaia belangeri ) has been used 151 . Specific beneficial aspects of this organism for studying HBV include the ability to support HBV entry and release from hepatocytes and establishment of chronic infection and cccDNA pools 152,153 .…”

Section: Animal Modelsmentioning

confidence: 99%

Experimental models of hepatitis B and C — new insights and progress

Thomas

Liang

2016

Nat Rev Gastroenterol Hepatol

125

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Viral hepatitis is a major cause of morbidity and mortality, affecting hundreds of millions of people worldwide. Hepatitis-causing viruses initiate disease by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma. Consequently, intense research efforts have been focusing on increasing our understanding of hepatitis virus biology and on improving antiviral therapy and vaccination strategies. Although valuable information on viral hepatitis emerged from careful epidemiological studies on sporadic outbreaks in humans, experimental models using cell culture, rodent and non-human primates were essential in advancing the field. Through the use of these experimental models, improvement in both the treatment and prevention of viral hepatitis has progressed rapidly; however, agents of viral hepatitis are still among the most common pathogens infecting humans. In this Review, we describe the important part that these experimental models have played in the study of viral hepatitis and led to monumental advances in our understanding and treatment of these pathogens. Ongoing developments in experimental models are also described.

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Section: Animal Modelsmentioning

confidence: 99%

Experimental models of hepatitis B and C — new insights and progress

Thomas

Liang

2016

Nat Rev Gastroenterol Hepatol

125

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“…[150] Genomic analysis has placed the treeshrew phylogenetically between humans and rodents, [151],[152] and this similarity to primates has spurred its use as a model for a broad range of studies, including as a model for viral hepatitis. [16, 153] Specifically, Tupaia belangeri has been used as a model to study the immediate effects of HBV infection on gene expression in the liver [16] and to identify genes potentially contributing to the development of HBV-associated HCC.…”

Section: Model Systems Used In the Study Of Hbvmentioning

confidence: 99%

Hepatitis B virus molecular biology and pathogenesis

Lamontagne¹,

Bagga²,

Bouchard³

2016

134

109

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As obligate intracellular parasites, viruses need a host cell to provide a milieu favorable to viral replication. Consequently, viruses often adopt mechanisms to subvert host cellular signaling processes. While beneficial for the viral replication cycle, virus-induced deregulation of host cellular signaling processes can be detrimental to host cell physiology and can lead to virus-associated pathogenesis, including, for oncogenic viruses, cell transformation and cancer progression. Included among these oncogenic viruses is the hepatitis B virus (HBV). Despite the availability of an HBV vaccine, 350–500 million people worldwide are chronically infected with HBV, and a significant number of these chronically infected individuals will develop hepatocellular carcinoma (HCC). Epidemiological studies indicate that chronic infection with HBV is the leading risk factor for the development of HCC. Globally, HCC is the second highest cause of cancer-associated deaths, underscoring the need for understanding mechanisms that regulate HBV replication and the development of HBV-associated HCC. HBV is the prototype member of the Hepadnaviridae family; members of this family of viruses have a narrow host range and predominately infect hepatocytes in their respective hosts. The extremely small and compact hepadnaviral genome, the unique arrangement of open reading frames, and a replication strategy utilizing reverse transcription of an RNA intermediate to generate the DNA genome are distinguishing features of the Hepadnaviridae. In this review, we provide a comprehensive description of HBV biology, summarize the model systems used for studying HBV infections, and highlight potential mechanisms that link a chronic HBV-infection to the development of HCC. For example, the HBV X protein (HBx), a key regulatory HBV protein that is important for HBV replication, is thought to play a cofactor role in the development of HBV-induced HCC, and we highlight the functions of HBx that may contribute to the development of HBV-associated HCC.

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“…Tree shrews ( Tupaia belangeri chinensis ) are small mammals that are susceptible to HBV infection, and the tree shrew animal model is a powerful tool for HBV research (17). In the present study, using the tree shrew animal model, we investigated the in vivo innate immune response to HBV.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles Including Exosomes Regulate Innate Immune Responses to Hepatitis B Virus Infection

et al. 2016

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The innate immune system is essential for controlling viral infection. Hepatitis B virus (HBV) persistently infects human hepatocytes and causes hepatocellular carcinoma. However, the innate immune response to HBV infection in vivo remains unclear. Using a tree shrew animal model, we showed that HBV infection induced hepatic interferon (IFN)-γ expression during early infection. Our in vitro study demonstrated that hepatic NK cells produced IFN-γ in response to HBV only in the presence of hepatic F4/80+ cells. Moreover, extracellular vesicles (EVs) released from HBV-infected hepatocytes contained viral nucleic acids and induced NKG2D ligand expression in macrophages by stimulating MyD88, TICAM-1, and MAVS-dependent pathways. In addition, depletion of exosomes from EVs markedly reduced NKG2D ligand expression, suggesting the importance of exosomes for NK cell activation. In contrast, infection of hepatocytes with HBV increased immunoregulatory microRNA levels in EVs and exosomes, which were transferred to macrophages, thereby suppressing IL-12p35 mRNA expression in macrophages to counteract the host innate immune response. IFN-γ increased the hepatic expression of DDX60 and augmented the DDX60-dependent degradation of cytoplasmic HBV RNA. Our results elucidated the crucial role of exosomes in antiviral innate immune response against HBV.Accession NumberAccession number of RNA-seq data is DRA004164 (DRA in DDBJ).

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<i>Tupaia Belangeri</i> as an Experimental Animal Model for Viral Infection

Cited by 31 publications

References 37 publications

Experimental models of hepatitis B and C — new insights and progress

Experimental models of hepatitis B and C — new insights and progress

Hepatitis B virus molecular biology and pathogenesis

Extracellular Vesicles Including Exosomes Regulate Innate Immune Responses to Hepatitis B Virus Infection

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