母婴传播中慢性乙型重型肝炎病毒相关变异的研究

Evolutionary tendency of chronic severe hepatitis B-related mutations in mother-to-child transmission of hepatitis B virus

目的研究乙型肝炎病毒基因(HBV DNA)pre S区内与慢性乙型重型肝炎(chronic severe hepatitis B,CSHB)相关变异在母婴传播过程中的进化趋势。方法收集879例HBs Ag阳性孕妇外周血,孕妇分娩后将其新生儿脐带血、完成乙肝疫苗注射后的7月龄婴儿外周血亦纳入队列。通过基因分型和系统发育分析鉴定HBV的母婴传播情况,运用单克隆测序方式检测母子体内HBV pre S区中CSHB相关突变情况。结果 HBV B/C基因型中CSHB相关变异C2875T、C2980T、G2988A、C3067T、C3097A、T25G、A76C、A79G、T100C、C102T、C106A、T109G、C135T、T147C、A148G,可通过宫内感染途径传播给新生儿;C2基因型中变异A3097C/G、G132C在HBV宫内感染中存在明显优势(P<0.05;P<0.05)。B2基因型中,变异C3057G、T3060C、C3097A、T3169A、A20G、A76C、C129T,能够通过MCTC途径由母亲传播给7月龄婴儿;C2基因型中以上变异突变率低。结论在母婴传播过程中,HBV B2基因型中CSHB相关变异较多;婴儿完成接种免疫后,野生型HBV在母婴传播中具有感染优势,进化具有保守性。

Objective To study the evolutionary tendency of chronic severe hepatitis B （CSHB）_ related mutations in the preS region of hepatitis B virus （HBV） during mother-to-child transmission. Methods Peripheral blood from HBsAg-positive mothers, umbilical cord blood from newborns, and peripheral blood from 7-month old infants who received intact vaccination were collected. Cloning sequencing was conducted to detect the viral mutations. Genotyping and phylogenetics analysis were conducted to determine the mother-to-child transmission of HBV. The Pearson Chi-square test and continuity correction were applied to evaluate the categorical variables. Results HBV strains with CSHB-related mutations C2875T, C2980T, G2988A, C3067T, C3097A, T25G, A76C, A79G, T100C,C102T , C106A , T109G , C135T , T147C and A148G could be transmitted to newborns through intrauterine pathway. HBV mutations includingA3097C/G and G132C had survival advantages in intrauterine transmission and chronicity （P 〈0.05 ; Z 5 〈0.05）. Genotype B2 HBV strains with mutations C3057G , T3060C , C3097A , T3169A , A20G , A76C , and C129T could be transmitted to 7-month old infants through mother to child transmission, while the similar phenomenon was not observed in genotype C2 HBV strains. Conclusion More CSHB-related mutations could be detected in genotype B2 HBV during mother- to-child transmission. After the immunization, HBV without the CSHB-related mutations has advantage of infecting infants and reflects the conservative nature on evolution perspectives of HBV.