Vertical Transmission Of Hepatitis B Virus Genome As Well As Its Mutation And Expression

Hepatitis B is caused by hepatitis B virus (HBV) infection.It is one of the most common and pilose diseases which endanger human health, and is associated with the occurrence of chronic active hepatitis,chronic progressive hepatitis, cirrhosis, and hepatocellular carcinoma. Nevertheless,there were no the clinical measures and strategy for treatment of hepatitis B with effective, and the incidence rate of HBV infection has no been degraded with significant up to now. Therefore, the transmitted types of HBV infection are followed with interest for researcher.It has not been demonstrated that hepatitis B may be vertically spread by germ cells. So far, few of such works have been done about the vertical transmission of hepatitis B genome between the hepatitis B parents and their children by germ cells(sperm and ovum).The genome of HBV is a small, circular, partially double-stranded DNA of about 3.2 Kb, which is replicated by reverse transcription of an RNA intermediate, termed pregenomic RNA.The organization of the viral genome is highly compact which contain four open reading frames of P,C,S and X.Every nucleotide is used at least once to code for a protein. The replication ,expression and mutation of gene in HBV genome of testicles in HBF and ovary in HBM were reported in the present study.The verticale transmission of HBV genome between hepatitis B fathers/mothers and their children, the construction of mouse ovum/sperm carriers with HBV genome and detection of transgenic mice with HBV genome were studied.The experimental evidences were provided for verticale transmission of HBV genome by sperm and ovum from the levels of molecular genetics ,cytobiology and histology.It was testified with the studies of hepatitis B patients and animals that germ cells infected with HBV can carry HBV genome to the children born after their parents suffered from hepatitis B.The proofs for theory of hepatitis B verticale transmission ,rationale and basis for intervention of HBV infection(for example,application of hepatitis B vaccine) were offered in this study .The detection rates of HBV genome with freed in serum and integrated in peripheral blood monouclear cells(PBMC) and HBV infectious rate in all experimental groups of hepatitis B father(HBF),children born after occurense of HBV infection(HBPa) and children born before occurense of HBV infection (HBPb) were first studied.It were discovered that 3 indexes above-mentioned in HBF and HBFa were significantly higher than that of HBFb and increased concordantly between the HBF and HBFa.It was directed that HBV genome in HBFa may be come from HBF.To analyse HBV genome mutation integrated in human genome of HBF and HBFa furthermore,the authors found that there was an abnormal ssDNA pattern with complete concordance by PCR-SSCP method between the fathers and children of HBF and HBFa. There were 3 loci of SNP mutation with complete concordance in the HBV genome U5-like region and non- U5-like region between the HBF and HBFa, and 10 loci of SNP mutation with complete concordance in the HBV genome U5-like region and non- U5-like region between the fathers with hepatitis B and their children born after infection of hepatitis B in family Nie. It was suggested that SNPs in HBV genome integrated in HBFa genome were transmitted from HBF genome integrated by HBV genome.The authors researched the HBV genome integrated in testicles and epididymis ,and found that a lot of HBV genomes were existed in HBF testicles and epididymis,which distributed in the basilar part of seminiferous tubules,in order to find out histological and cytological evidences of HBF testicles and epididymis generated sperm.Therefore,the evidences of histology and cytology for vertical transmission between the HBF and HBFa was provided. It was reported first time that the present study on vertical transmission of HBV genome between the hepatitis B fathers and their children born after occurrence of hepatitis B in the abroad and domestic.HBV genome expression integrated in ovary cells of HBM with positive of HBsAg and HBeAg was studied and HBsAg distribution and expression in ovary tissues of HBM with positive of HBsAg and HBeAg were detected. The authors found that HBsAg distributed in the walls of blood vessel and peripheral interstitial cells of ovary,and was detected in follicular cytoplasm of cortex ovarii.It was demonstrated that HBV genome was existed in ovary and follicular cells infected with HBV.The histogical and cytological evidences of vertical transmission of HBV genome between the HBMs and their infants were provided.,HBV genome existed in ovaries and peripheral blood of HBM and in cord blood of HBM newborns were analysed, furthermore.HBV genome was detected in HBM ovaries. The detected rates of HBV genome in HBM ovaries and in cord blood of HBM newborns were increased with concordance which were significantly higher than normal control.It was shown that HBV genome in HBM newborns may be come from HBM by ovums caught HBV, because the histological and cytological basis was provided from HBV genome of ovary cells in HBM by the study of immunohistochemistry。Meanwhile,HBV genome and its distribution of HBM ovaries with paraffin tissue section were analysed and detected in HBM ovaries, which was distributed in follicular cells of cortex ovarii,blood vessel walls in ovary hylic.It was elucidated too that the ovaries were infected with HBV, and HBV genome was existed in ovary tissues and ollicular cells.Thus, the histological and cytological evidences were offered for vertical transmission of HBV genome between HBMs and their newborns. It was reported first time that the present study on vertical transmission of HBV genome between the hepatitis B mothers and their children born after occurrence of hepatitis B in the abroad and domestic. It is obviously impossible to make use of human germ cells for studying vertical transmission of HBV genome because of ethics problem. The mouse ovum was caught by positive ion liposome-plasmid PBR322-HBV DNA.HBV genome carried by liposome can entered into the mouse ovum which may act as the HBV genome carriers It provided basic conditions for cultivating animal model which transmitted HBV genome to their offsprings by ovum.The mouse sperm was cotransfected with the methods of sperm carrier and in vivo transfection. The authors found that the mouse sperm can have some ability of capturing HBV genome ,where distributed in the sperm.The transgenic mouse model was raised by the method of sperm carrier for vertically transmitting HBV genome by sperm..The experimental evidences were offered for vertical transmission of HBV genome by germ cells and for vertical spread of HBV infection.The study of vertical transmission of HBV genome will conduce to elucidate the mechanisms and pathways of HBV infection.The theory and fundament will be provided for clinical prevention,except breakthrough of theory in hepatitis B transmission. There will be an important significance in many directions of cutting down the incidence rate of hepatitis B, elevating the people procatarxis,rearing better children and aristogenesis.