Zampino Rosa, Lobello Salvatore, Chiaramonte Maria, Venturi-Pasini Carla, Dumpis Uga, Thursz Mark, Karayiannis Peter
Department of Medicine A, Imperial College School of Medicine at St. Mary's, South Wharf Road, London W2 1NY, UK.
J Hepatol. 2002 Feb;36(2):248-53. doi: 10.1016/s0168-8278(01)00253-7.
BACKGROUND/AIMS: Transmission of hepatitis B virus (HBV) in countries of intermediate endemicity, such as Italy, is thought to be primarily horizontal and, to a lesser extent, vertical. Most chronic carriers therefore become infected in infancy or at a very young age. The index cases in such events have been assumed to come from within the family unit or from sources outside the immediate family, with whom the affected person is in close contact.
We studied a number of Italian families with multiple members chronically infected with HBV. The precore/core region of the virus was amplified from serum derived HBV-DNA, and the sequences subjected to phylogenetic tree analysis. In addition, the extent of amino-acid variation within the core region was correlated to HLA type, determined by allele-specific PCR.
The phylogenetic tree analysis provided strong evidence of intra-familial transmission of the virus. Analysis of amino-acid substitutions in the core region in relation to HLA class II alleles from members of the same family showed that these substitutions were restricted in siblings with concordant, and more diverse in those with discordant HLA haplotypes.
This is consistent with major histocompatibility complex class II mediated selection pressure on the virus.
背景/目的：在中等流行程度的国家，如意大利，乙型肝炎病毒（HBV）的传播被认为主要是水平传播，垂直传播的程度较小。因此，大多数慢性携带者在婴儿期或非常年幼时就被感染。此类事件中的索引病例被认为来自家庭单位内部或直系家庭以外的来源，与受影响者有密切接触。
我们研究了许多有多名成员慢性感染HBV的意大利家庭。从血清来源的HBV-DNA中扩增病毒的前核心/核心区域，并对序列进行系统发育树分析。此外，核心区域内氨基酸变异的程度与通过等位基因特异性PCR确定的HLA类型相关。
系统发育树分析提供了病毒家族内传播的有力证据。对来自同一家族成员的核心区域氨基酸替代与HLA II类等位基因的分析表明，这些替代在具有一致HLA单倍型的兄弟姐妹中受到限制，而在具有不一致HLA单倍型的兄弟姐妹中则更多样化。
这与主要组织相容性复合体II类介导的对病毒的选择压力一致。
