| Hepatitis B virus (HBV) infection is a global health problem. After20years ofvaccination, the carrier rate of HBsAg among children has decreased markedly. However,intrauterine transmission is the main cause of vaccination failure, which cannot beinterrupted by the HBV vaccination. Neonates infected with HBV in this way will mostlycarry the virus for their entire lifetime, and10–25%of them will probably develop cirrhosisand hepatocellular carcinoma.Female babies will be most likely to transmit the virus totheir offspring through pregnancy in the future. The main routes of intrauterinetransmission include transplacental transmission, and transmission of peripheral bloodmononuclear cells,（PBMCs） and germ cells，in which “placental leakage” and “cellularroute” are most important. HBeAg can pass through the placenta via partial placentalleakage, with the breakdown of the placental barrier resulting in leakage of maternal bloodinto the fetal circulation, or via the “cellular route”, possibly contributing to transplacentaltransmission of the infection. It is positively associated with maternal HBeAg-positiveserological status and high maternal viral load as well as with placental HBV infection. Butthe babies undergoing risk factors were that "some were in chronical infectied status, butothers can produce protective antibody".According to the phenomenon, Etiologycharacteristic (HBV genotype, serum type, quasispecies) and environment factors and thegenetic factors of host(susceptibility,gene polymorphism, predisposing genes) maybe playan important role respectively, and more possibily the result of interaction.The diversity, evolution rateand the development direction of HBV in patients duringpregnancy also changed. Virus may form the immune-escape variants under the selectionpressure and infecte placenta.Finally,the plants infecte intrauterine fetal via breakingthrough the barrier of placenta. In the new environment,what are the characters of the virusin the population evolution and nucleotide polymorphism distribution? Which is the rule ofeach protein coding areas while evolution? These problems are still lack of a large numberof studies. The full HBV genome contains four partially overlapping open reading frames(ORFs)，Separately coding surface antigen (S area), polymerase (P area), the core antigen(area C) and X protein (X area).The virus mutation is affected by the interaction of its ownviral replication characteristics, the genetic background of host, the immune pressure, andetc. For HBV copys and spreads with the full-length seqencese for hereditary unit,dynamicchanges within other regions (especially in the immune-targeted surface and core antigen)might also be informative, and comparison of the full genome is necessary.In the present study,we collect two pair of high mother and neonates venous bloodsamples who occurring intrauterine transmission with high load of virus (HBV DNA≥106copies/ml) and HBsAg and the HBeAg are positive, and investigate the evolutioncharacters of HBV between mother and neonates by PCR-sequencing clone-phyleticevolution analysis method. Meanwhile, With the two mothers as the case group, and themothers who have the same charaters of virus but not occurring intrauterine transmission ascontrol group, We use the same methods to observe the heterogeneity of HBV sequencechanges between the two groups, and to analysis the rule of variation and evolution infull-length of HBV sequences， thus to discusses the role of hepatitis B virus quasispeciesheterogeneity during Mother to Infant Transmissin of Hepatitis B Virus.Main Results1. The two phylogenetic trees included two features. In the first feature, most of thematernal sequences clustered into one clade, the neonatal sequences and some of maternalsequences clustered into another clade.One of maternal strains were the ancestor of theneonatal strains In the second feature, the sequences of the mothers and neonates couldform neither a monophyletic cluster nor separate monophyletic clusters.One of the neonatalstrains was in the upstream of clade including most strains of mother and neonate.2. The phylogenetic of HBV has their own features between the control group and thecase group, The feature of “placenta leakage” approach to those of the control group.3. There is no different between cases group and control group population geneticdistance between mean distance by two sample t-test (P>0.05),but it is different whilecompare with the population of the each internal matching the pariwise genetic distancedatabase,(P <0.05).4. U1has the highest gene polymorphism, the genetic polymorphism of U4and M1are higher, U2is smilar to U3, and the gene polymorphism of M2is minimal. RT area, X areaand the former C/C area and former S/S area are genetic polymorphism distribution. thehighest genome polymorphism peak of U1is in the preS area; Those of M1is in the S area(and RT area overlap, nt378-480between), X area and former C/C area have peakdistribution also, and the highest is located in former C/C area; The peak of U2, U3and U4district are uniformly distributed, the highest peak in X area or former C/C area, The wholegenome sequence of nucleotides overall polymorphism of M2is not significant, the highestpeak in S area (and RT area overlap, nt431-619between).5. In the evolution process, The synonymous replace (dN) and synonymousreplacement (dS) distance of each ORF within each sample are not the same.6. Positive selection sites of each samples were not found.Main conclusion1.The characters of the molecular evolution of the two cases were separatelyaccorded with those of “placental leakage” and “cellular route”.2. There is no different between cases group and control group population geneticdistance between mean distance by two sample t-test (P>0.05),but it is different whilecompare with the population of the each internal matching the pariwise genetic distancedatabase,(P <0.05). It explains the properties of quasispecies HBV.3. The the plant populations which transmit by “cellular route” has the smaller geneticdistance and nucleotide polymorphism, the significant nucleotide polymorphism district islocated in the the S gene which relate to antigens and immune escape, with "a" antigendeterminant.“sT126A” is a hot Amino acids variation site related to Immunization escape It isshowed that S gene and "a" antigen determinant maybe play a role in the intrauterinetransmission.4. In the evolution process, The synonymous replace (dN) and synonymousreplacement (dS) distance of each ORF within each sample are not the same.Itis showedthat the stress response of coding areas to choice pressure are different.5. The quasispecies heterogeneity of HBV transmited via “cellular route” is less thanthat of HBV transmited via “placenta leakage” and untransmitted. |
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