Abstract
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.
Highlights
Epstein–Barr virus (EBV) is closely associated with many human diseases, including a variety of deadly human malignant tumours
Based on previous research and on the high similarity of tree shrews to primates, we proposed that tree shrews will be susceptible to Epstein-Barr virus infection and that they possess good potential for use as an animal model of EBV infection in humans
Thirteen tree shrews were used in this study, including 10 inoculated with 500 μl of EBV by intravenous injection and 3 inoculated with RPMI 1640 culture medium containing 10% foetal bovine serum using a similar procedure
Summary
Epstein–Barr virus (EBV) is closely associated with many human diseases, including a variety of deadly human malignant tumours. We established tree shrews as a model for EBV infection by intravenous injection. When EBV infects restingstate B cells, it often establishes latency III and expresses all latent genes, including 3 latent membrane protein genes (LMPs), 6 nuclear antigen genes, and 2 nonprotein-encoding RNAs (EBERs, EBER-1and EBER-2) [4]. When the memory B cells that carry EBV enter the germinal centre B cells (centroblasts and centrocytes), latency II emerges with limited latent gene expression (LMPs, EBNA1, BARTs and EBERs). Latency I, which involves EBNA1 and EBERs expression,has been detected in proliferating memory B cells, and latency 0, without EBV protein expression but with the presence of nontranslated viral RNAs, was demonstrated in resting memory B cells [5]. EBV can transform human peripheral blood B cells to EBV-infected latency III immortalized cell lines
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