Department of Infectious, Parasitic and Immune-mediated Diseases (MIPI), Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Infection. 2014 Aug;42(4):675-87. doi: 10.1007/s15010-014-0616-2. Epub 2014 Apr 4.
Human immunodeficiency virus (HIV-1)-infected patients frequently harbour hepatitis B and C viruses (HBV and HCV, respectively). Possible modifications of the natural history of hepatitis B may occur. The aim of this study was to characterise HBV diversity and evolutionary and mutational viral genome profiles in HIV-1/HBV coinfections.
HIV-1 and HBV markers determinations (Roche, FRG; Abbott, USA) and HBV genome-length retrospective analysis were performed in follow-up isolates from patients who were either stably HBsAg-negative with a low level of HBV DNA (occult hepatitis B infection, OBI) or HBsAg-positive with a high level of HBV DNA. Phylogenetic analysis (maximum likelihood method, MEGA5), statistical analysis and evolutionary rates calculation (d S/d N) were applied.
Positive selection pressures in the PreS/S region and a significantly higher number of mutations in this region including the major hydrophilic region (MHR) and the "a" determinant were shown in HBsAg-negative (possibly OBI) compared to stably HBsAg-positive HIV-1/HBV subgenotypes D3/A2 coinfected patients. Mutants previously described in HIV-1/HBV coinfected patients were found. Known mutants Y100C, P127T and P120A associated to Y134H and S143T and new S mutants, which may potentially affect HBsAg expression and secretion and anti-HBs binding, were detected in baseline sera persisting up to the end of 9 years follow-up. Known mutations of BCP, Pre-C, C and X regions were also characterised. Natural mutants strictly known as being involved in diagnostic failure were not detected; however, numerous corresponding sites showed amino acid variations.
Evolutionary and genotypic differences observed, particularly in the PreS/S region, between HBsAg-negative (OBI) and HBsAg-positive HIV-1/HBV coinfected patients, may contribute, in association with mutations of other genomic regions, to the HBsAg-negative phenotype.
人类免疫缺陷病毒（HIV-1）感染患者常同时感染乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）。HBV 的自然史可能发生改变。本研究旨在描述 HIV-1/HBV 合并感染患者中 HBV 多样性以及病毒基因组进化和突变特征。
采用罗氏（FRG）和雅培（美国）的检测试剂，对随访患者的 HIV-1 和 HBV 标志物进行检测，并对 HBV 全基因组进行回顾性分析。这些患者要么持续 HBsAg 阴性且 HBV DNA 水平较低（隐匿性乙型肝炎感染，OBI），要么 HBsAg 阳性且 HBV DNA 水平较高。应用最大似然法（MEGA5）进行系统进化分析、统计学分析和进化率计算（dS/dN）。
与持续 HBsAg 阳性的 HIV-1/HBV 亚基因型 D3/A2 合并感染者相比，HBsAg 阴性（可能为 OBI）患者的 PreS/S 区存在正选择压力，且该区域的突变数量明显更多，包括主要亲水区（MHR）和“a”决定簇。在 HIV-1/HBV 合并感染者中发现了先前描述的突变株。在基线血清中检测到与 Y134H 和 S143T 相关的 Y100C、P127T 和 P120A 以及新的 S 突变株，这些突变株可能潜在影响 HBsAg 的表达和分泌以及抗-HBs 结合，这些突变株在 9 年的随访结束时仍持续存在。还对 BCP、Pre-C、C 和 X 区的已知突变进行了特征描述。未检测到严格意义上与诊断失败相关的天然突变株，但许多相应的位点显示出氨基酸变异。
在 HBsAg 阴性（OBI）和 HBsAg 阳性的 HIV-1/HBV 合并感染者之间，观察到 PreS/S 区域的进化和基因型差异，这些差异可能与其他基因组区域的突变一起导致 HBsAg 阴性表型。
