Molecular and serological characterization of hepatitis B virus genotype A and D infected blood donors in Poland

Molecular and serological characterization of hepatitis B virus genotype A and D infected blood donors in Poland
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DOI:
10.1111/j.1365-2893.2009.01192.x
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发表时间:
2010-06-01
影响因子:
2.5
通讯作者:
Allain, J. -P.
Allain, J. -P.
中科院分区:
医学3区
文献类型:
--
作者:
Grabarczyk, P.;Garmiri, P.;Allain, J. -P.

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B型肝炎病毒(HBV)基因型具有不同的地理分布,并影响临床结果的严重程度和抗病毒治疗的反应。对来自波兰的首次献血者中HBV表面抗原(HBsAg)阳性者的HBV多态性进行了检测。对170例标本进行HBV血清学标志物和HBV DNA检测。全基因组(n = 53)或特定区域序列:前S/S和基本核心启动子/前核心(BCP/PC)区域(分别为91和154个样品)进行了遗传学分析。受感染献血者的中位年龄为21岁。抗-HBs、抗-HBe和B e抗原的检出率分别为5%、92.4%和10.5%。HBV DNA载量范围为不可定量至3.1 × 1010 IU/mL(中位数:4.10 × 103 IU/mL)。基因型A2(81.2%)和D(18.8%)共循环。系统发育分析揭示了基因型之间的差异。D基因型的病毒载量和HBsAg水平有降低的趋势。两种基因型的HBsAg/HBV DNA比值中位数(IU/mL)均为1,但极低或极高的比值在D型感染中更常见。在D基因型中观察到表面蛋白的氨基酸变异性更高(中位数:4%vs 1.5%; P = 0.01),主要亲水区域的氨基酸变异性更高(P = 0.01)。BCP/PC区分析显示A2型49/125株(39.2%)和D型6/29株(20.7%)存在1762 T/1764 A双突变(P = 0.08)。PC和BCP区的突变与HBsAg和HBV DNA水平均不相关。在波兰,HBV基因型A2在HBsAg阳性献血者中占优势。少数基因型D菌株比基因型A2菌株具有显著更多的替代性,可能影响感染过程。
Hepatitis B virus (HBV) genotypes have distinct geographical distributions and influence severity of clinical outcome and response to antiviral therapies. HBV polymorphism in HBV surface antigen (HBsAg) positive first time blood donors from Poland was examined. HBV serological markers and HBV DNA were tested in 170 samples. Whole genome (n = 53) or specific region sequences: pre-S/S and basic core promoter/precore (BCP/PC) region (91 and 154 samples, respectively) were phylogenetically analyzed. The median age of infected donors was 21 years. Anti-HBs, anti-HBe and hepatitis B e antigen were detected in 5%, 92.4% and 10.5% of tested donors, respectively. The HBV DNA load ranged between unquantifiable and 3.1 x 1010 IU/mL (median: 4.10 x 103 IU/mL). Genotypes A2 (81.2%) and D (18.8%) co-circulated. Phylogenetic analyses revealed differences between the genotypes. Viral load and level of HBsAg tended to be lower in genotype D. The median HBsAg/HBV DNA ratio expressed in IU/mL was one for both genotypes, but very low or very high ratios appeared more frequent in genotype D infections. Higher amino acid variability in the surface proteins (median: 4%vs 1.5%; P = 0.01) and in the major hydrophilic region was observed in genotype D (P = 0.01). BCP/PC region analysis revealed the double mutation 1762T/1764A in 49/125 (39.2%) genotype A2 and 6/29 (20.7%) genotype D strains (P = 0.08). Mutations in PC and BCP regions correlated neither with HBsAg nor HBV DNA levels. HBV genotype A2 is dominant in HBsAg positive donors in Poland. Minority genotype D strains are significantly more substituted than genotype A2 strains potentially affecting the course of infection.