Healthy rabbits are susceptible to Epstein-Barr virus infection and infected cells proliferate in immunosuppressed animals

Khan, Gulfaraz; Ahmed, Waqar; Philip, Pretty S.; Ali, Mahmoud H; Adem, Abdu

doi:10.1186/s12985-015-0260-1

Cited by 22 publications

(47 citation statements)

References 66 publications

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“…Rabbits have been also used to recapitulate features of EBV infection in humans [6]. Intravenous inoculation of EBV to New Zealand White rabbits followed by immunosuppression with cyclosporine A induced proliferation of EBV-positive lymphoblasts with the latency III type of viral gene expression in the spleen and the liver, indicating the possibility of using rabbits as a model of EBV-associated LPD [17]. The lineage (B or T) of EBV-infected lymphoblasts was not identified in this study.…”

Section: Ebv-positive Lpd In Laboratory Animals Induced By Experimentmentioning

confidence: 99%

Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis

Fujiwara

Nakamura

2020

Pathogens

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Epstein–Barr virus (EBV) is involved in the pathogenesis of various lymphomas and carcinomas, whereas Kaposi’s sarcoma-associated herpesvirus (KSHV) participates in the pathogenesis of endothelial sarcoma and lymphomas. EBV and KSHV are responsible for 120,000 and 44,000 annual new cases of cancer, respectively. Despite this clinical importance, no chemotherapies or vaccines have been developed for virus-specific treatment and prevention of these viruses. Humans are the only natural host for both EBV and KSHV, and only a limited species of laboratory animals are susceptible to their experimental infection; this strict host tropism has hampered the development of their animal models and thereby impeded the study of therapeutic and prophylactic strategies. To overcome this difficulty, three main approaches have been used to develop animal models for human gammaherpesvirus infections. The first is experimental infection of laboratory animals with EBV or KSHV. New-world non-human primates (NHPs) and rabbits have been mainly used in this approach. The second is experimental infection of laboratory animals with their own inherent gammaherpesviruses. NHPs and mice have been mainly used here. The third, a recent trend, employs experimental infection of EBV or KSHV or both to immunodeficient mice reconstituted with human immune system components (humanized mice). This review will discuss how these three approaches have been used to reproduce human clinical conditions associated with gammaherpesviruses and to analyze the mechanisms of their pathogenesis.

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Section: Ebv-positive Lpd In Laboratory Animals Induced By Experimentmentioning

confidence: 99%

Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis

Fujiwara

Nakamura

2020

Pathogens

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“…Ten tree shrews were inoculated with EBV by intravenous injection of 500μl of the viral solution described previously. The EBV copy number in the inoculums was approximately 3.9 × 10 8 copies per animal as confirmed by real-time quantitative PCR(qPCR).The infectivity of the virus in the viral solution was assessed by its ability to successfully immortalize human PBMCs in vitro [ 25 , 58 ]. The10 tree shrews inoculated with EBV were designated Ts1-Ts10.…”

Section: Methodsmentioning

confidence: 99%

“…Studies of EBV using transgenic animal models have focused on individual genes such as EBNA1 and LMP1 [ 20 – 22 ]. Recent studies have confirmed that rabbits can be infected with EBV via venous and nasal inoculation [ 23 – 25 ] and that EBV can infect rabbit B cells in vitro [ 26 ]. Although these animal models have played important roles in studying the EBV infection process, its pathogenic mechanism, and its prevention and treatment, they also present some disadvantages.…”

Section: Introductionmentioning

confidence: 99%

A study of Epstein-Barr virus infection in the Chinese tree shrew(Tupaia belangeri chinensis)

Zhi

Xiang

et al. 2017

Virol J

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BackgroundEpstein–Barr virus (EBV) is closely associated with many human diseases, including a variety of deadly human malignant tumours. However, due to the lack of ideal animal models,the biological characteristics of EBV, particularly its function in tumourigenesis, have not been determined. Chinese tree shrews (Tupaia belangeri chinensis), which are similar to primates, have been used to establish a variety of animal models and have recently received much attention. Here, we established tree shrews as a model for EBV infection by intravenous injection.MethodsTen tree shrews were inoculated with EBV by intravenous injection,and blood was collected at regular intervals thereafter from the femoral artery or vein to detect EBV markers.ResultsEight of 10 tree shrews showed evidence of EBV infection. In the 8 EBV-infected tree shrews, EBV copy number increased intermittently or transiently, EBV-related gene expression was detected, and anti-EBV antibodies increased to varying degrees. Macroscopic hepatomegaly was observed in 1 tree shrew, splenomegaly was observed in 4 tree shrews, and enlarged mesenteric lymph nodes were observed in 3 tree shrews. Haematoxylin and eosin (HE) staining showed splenic corpuscle hyperplasia in the spleens of 4 tree shrews and inflammatory cell infiltration of the liver of 1 tree shrew and of the mesenteric lymph nodes of 3 tree shrews. EBER in situ hybridization(ISH) and immunohistochemical (IHC) staining showed that EBER-, LMP1- and EBNA2- positive cells were present in the spleens and mesenteric lymph nodes of some tree shrews. Western blotting (WB) revealed EBNA1-positive cells in the spleens of 4 tree shrews. EBV markers were not detected by HE, EBER-ISH or IHC in the lung or nasopharynx.ConclusionsThese findings suggest that EBV can infect tree shrews via intravenous injection. The presented model offers some advantages for exploring the pathophysiology of EBV infection in humans.

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“…Sections were counterstained with haematoxylin, dehydrated and mounted for microscopic analysis. Formalin-fixed paraffin embedded sections from an EBV infected rabbit spleen [ 33 ] were included as a positive control.…”

Section: Methodsmentioning

confidence: 99%

No evidence for the presence of Epstein-Barr virus in squamous cell carcinoma of the mobile tongue

et al. 2017

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Squamous cell carcinoma of the head and neck (SCCHN) comprises a large group of cancers in the oral cavity and nasopharyngeal area that typically arise in older males in association with alcohol/tobacco usage. Within the oral cavity, the mobile tongue is the most common site for tumour development. The incidence of tongue squamous cell carcinoma (TSCC) is increasing in younger people, which has been suggested to associate with a viral aetiology. Two common human oncogenic viruses, human papilloma virus (HPV) and Epstein-Barr virus (EBV) are known causes of certain types of SCCHN, namely the oropharynx and nasopharynx, respectively. EBV infects most adults worldwide through oral transmission and establishes a latent infection, with sporadic productive viral replication and release of virus in the oral cavity throughout life. In view of the prevalence of EBV in the oral cavity and recent data indicating that it infects tongue epithelial cells and establishes latency, we examined 98 cases of primary squamous cell carcinoma of the mobile tongue and 15 cases of tonsillar squamous cell carcinoma for the presence of EBV-encoded RNAs (EBERs), EBV DNA and an EBV-encoded protein, EBNA-1. A commercially available in situ hybridisation kit targeting EBER transcripts (EBER-ISH) showed a positive signal in the cytoplasm and/or nuclei of tumour cells in 43% of TSCCs. However, application of control probes and RNase A digestion using in-house developed EBER-ISH showed identical EBER staining patterns, indicating non-specific signals. PCR analysis of the BamH1 W repeat sequences did not identify EBV genomes in tumour samples. Immunohistochemistry for EBNA-1 was also negative. These data exclude EBV as a potential player in TSCC in both old and young patients and highlight the importance of appropriate controls for EBER-ISH in investigating EBV in human diseases.

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Healthy rabbits are susceptible to Epstein-Barr virus infection and infected cells proliferate in immunosuppressed animals

Cited by 22 publications

References 66 publications

Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis

Animal Models for Gammaherpesvirus Infections: Recent Development in the Analysis of Virus-Induced Pathogenesis

A study of Epstein-Barr virus infection in the Chinese tree shrew(Tupaia belangeri chinensis)

No evidence for the presence of Epstein-Barr virus in squamous cell carcinoma of the mobile tongue

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