动物造模,乙肝病毒模型 z-bio 2021-12-16 332

　　Duck hepatitis B virus (DHBV) was introduced in 1980 by William et al. be found. Later, the virus was found in ducks, herons and wild geese from various sources. The host range of avian influenza hepatitis B virus is very narrow. For example, DHBV only infects birds, such as ducks and swans, and does not infect American ducks and chickens.

　　Human hepatitis B virus and avian hepatitis virus have many things in common. Both viruses carry part of the double-helical DNA genome. Genome replication depends on the presence of RNA intermediates. There is a lot of overlap between coded frames. Gene region. In addition, these two viruses have a lot in common in terms of genome and virus structure, replication and virus life cycle. Both viruses are liver viruses. Many infectious characteristics of liver nutrition viruses have been found in the DHBV model. For example, viral genome replication includes the reverse transcription of RNA intermediates, the formation and amplification of covalently closed circular cccDNA, and reverse transcription; as well as the determinants of the direction of the virus host, these are the biological characteristics of HBV and are important for research. The reference meaning.

　　At the same time, there are some differences between DHBV and HBV: DHBV genome is slightly smaller than animal hepatitis B virus, and the nucleotide sequence homology between the two is about 40%; DHBV genome is Box, which lacks coding for avian hepatitis B The X gene of the virus has only two envelope proteins instead of three. When DHBV infects eggs through female ducks, the infection usually leads to chronic infection, but viral infection usually does not cause liver damage, nor does it cause liver disease or liver cancer. Ducks can be healthy for life; adult ducks get rid of DHBV infection; when DHBV is passed from female ducks to young ducks, it can cause chronic infections, which can cause most liver damage, as well as liver cancer or cirrhosis. After adult ducks are infected with DHBV, if the virus cannot be eliminated, it may lead to the development of acute hepatitis. Except for HepaRG (a human liver cell line isolated from non-tumor tissues of liver cancer patients infected with chronic hepatitis C virus), only primary duck liver cells are sensitive to DHBV. Therefore, the in vitro replication of DHBV depends on primary cultured hepatocytes. DHBV can replicate in primary cultured duck or adult duck liver cells. Duck fetal liver cells are easily obtained from duck embryos that have never hatched, and can be washed and cultured after the liver tissue is digested with collagenase. Of course, this cell line contains cells other than liver parenchyma, such as macrophages and fibroblasts. In addition, the primary hepatic cell line of adult duck is obtained by perfusing the liver of adult duck, but the hepatic cell line obtained by this method is relatively pure (the number of hepatocytes reaches more than 90%). Primary liver cell lines can be cultured in standard media containing hydrocortisone, insulin and DMSO, but DMSO is very important for maintaining liver cell differentiation and virus sensitivity. Using an in vitro model of DHBV infection, the researchers found many detailed links related to the hepatitis virus replication cycle. The advantage of establishing a duck hepatitis B virus animal model is that ducks can be easily tested in animals. In addition, DHBV-sensitive primary hepatocytes can be easily isolated from suckling ducks and embryos. The use of DHBV-infected ducks as a model is mainly used to study the role of virus cccDNA as an RNA transcription template in virus replication. Although ducks will not develop liver cancer after being infected by DHBV, there are still scholars studying the role of virus replication in cancer development by integrating the viral genome into the cell chromosomes of cell tumor models.

　　is similar to the onset of human infection with HBV. After ducks are infected with DFBV, the course of the disease is related to age. Generally speaking, hepatitis virus infection can develop into acute or chronic infection. The result of infection is related to the amount of virus used at the time of infection. High-dose virus infection will increase the possibility that newborn ducks will continue to be infected. The production of neutralizing antibodies in the course of infection also determines the different course of disease development in newborns and adult ducks after viral infection. Adult ducks will quickly produce neutralizing antibodies and can effectively prevent the spread of the virus in the liver.

　　Under normal circumstances, DHBV can transmit duck eggs vertically from female ducks, causing chronic infection in newborn ducks. However, due to the immune system's resistance to the virus, the animal has no symptoms. Therefore, all ducklings born from DHBV-positive female ducks are DHBV-positive. In chronically infected ducks, DHBV mainly replicates in liver cells. Under normal circumstances, the level of virus replication is very high. Almost all hepatocytes are infected and express viral antigens, and a large number of viral antigens can be detected in the peripheral blood, up to 10 copies per milliliter, and the virus can also be detected . At the same time, the DHBV model is also used to study the hepatitis B virus cell receptor, the growth curve of virus variants, and the in vivo and in vitro evaluation of antiviral drugs. However, it has been found that ducks differ from woodchucks in that they are not sensitive to the toxicity of antiviral drugs. The duck's metabolic system is compatible with the metabolic process of antiviral drugs. Therefore, due to the difference between the virus and the host hepatocytes, the clinical application value of drugs evaluated through the duck hepatitis B virus model is still limited.