Human hepatitis B virus and hepatocellular carcinoma I. Experimental infection of tree shrews with hepatitis B virus

Abstract

Tree shrews (Tupaia belangeri chinenesis) can be experimentally infected with human hepatitis B virus (HBV) by inoculation with human serum positive for HBV, the experimental infection rate being 55.21%. Successive infections have been passed through five generations among the tree shrews inoculated with HBV-positive sera from the infected animals, the average infection rate being 94.0%. The experimental infection of tree shrews with HBV may be prevented by immunization with hepatitis B vaccine, the protection rate being 88.89%. Standard serum containing HBV at 10(8) CID (chimpanzee infection dose)/ml, was diluted 10(-6), 10(-7), 10(-8), 10(-9), and 10(-10) and produced infection rates of 80.0%, 88.8%, 66.7%, 55.6% and 42.9% respectively. Thus the CID50 in tree shrews may reach a dilution of 10(-9), which shows that tree shrews are sensitive to HBV infection. These results successfully establish tree shrews as a reliable and useful animal model for research on HBV infection and its relation to hepatocarcinogenesis.

Genome of the Chinese tree shrew

“…3 and Supplementary Data 2) provided helpful information for us to explain why this animal could be used to create animal model for viral infection. Although we did not provide independent infection experiments (either the animal or primary hepatocytes) to prove its susceptibility, the plenty of previous reports on HBV 4 and HCV 3 infection would certify tree shrews' susceptibility to these viruses. Nonetheless, the findings for the absence of DDX58 gene and other unique gene features in tree shrew would account for the distinct immune response involved in viral hepatitis.…”

“…The publicly available annotated genome sequence of the Chinese tree shrew we generated offers an opportunity to decipher the genetic basis of the tree shrews' suitability as an animal model for studying depression, myopia and viral infection [3][4][5][6][7] . Although we did not provide further experimental evidence to solidify the speculations deducted from the comparative genomics, the unique genetic features that we discerned from the genome of Chinese tree shrew has provided insightful information for us to understanding the biology of this animal.…”

“…Currently, there are many attempts to employ tree shrew to create animal models for studying hepatitis C virus (HCV) 3 and hepatitis B virus (HBV) infections 4 , myopia 5 , as well as social stress and depression 6,7 . Recent studies of aged tree shrew brain suggested that tree shrew is also a valid model for aging research 8 and learning behaviours 9 .…”

Treeshrews, the primitive primate mammals for medical experimental animals

“…Two human virus infection models, hepatitis C virus (HCV) and hepatitis B virus (HBV), have been established (Yan et al, 1996, Zhao et al, 2002; myopia research model (Norton et al, 2006), social stress and depression research model (Fuchs, 2005;Kampen et al, 2002) and the models of aging and learning behaviors (Yamashita, et al, 2012;Bartolomucci et al, 2002) have been reported as well. Obviously, with the advances in modern molecular biology, especially in the development of next-generation genome sequencing technology, the deciphering of the genetic code of treeshrews will make treeshrews become an important alternative for medical research and drug trials alternative to nonhuman primates.…”

Expression of p53 gene in hepatocellular carcinomas induced by aflatoxin B1 with or without human hepatitis B virus in tree shrews

“…On the basis of their results, we investigated the hepatocarcinogenesis of AFB 1 and human HBV (HHBV) in this species ( Yan et al, 1996a( Yan et al, , 1996b. The results indicated that the HCC incidence was significantly higher in the tree shrews exposed to both HHBV and AFB 1 than in those which received either HHBV infection or AFB 1 ingestion only.…”