Expression of human herpesvirus 8 in primary pulmonary hypertension
Expression of human herpesvirus 8 in primary pulmonary hypertension
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DOI：
10.1056/nejmoa035115
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发表时间：
2003-09-18
影响因子：
158.5
通讯作者：
Voelkel, NF
中科院分区：
文献类型：
--
作者：
Cool, CD;Rai, PR;Voelkel, NF
背景：重度肺动脉高压是一组以复杂的管腔闭塞性血管病变为特征的疾病，发生在遗传易感人群中。唯一与严重肺动脉高压相关的病毒感染是由人类免疫缺陷病毒1型引起的，但在病理病变中都没有发现病毒基因组和病毒抗原。方法：我们检测了16例散发性原发性肺动脉高压患者和14例继发性肺动脉高压患者的肺组织样本，以寻找感染人类疱疹病毒8 （HHV-8）的证据。使用针对潜伏期相关核抗原1 （LANA-1）的抗体免疫组织化学方法确定HHV-8感染，并对肺DNA进行聚合酶链反应（PCR）检测HHV-8病毒周期蛋白基因。同时进行序列分析。结果：在16例原发性肺动脉高压患者中，有10例（62%）的肺组织在免疫组化分析中，网状病变内的细胞以及病变外的细胞LANA-1呈阳性。PCR分析显示，同样10例患者的组织中含有病毒周期蛋白。继发性肺动脉高压患者的肺组织中未检测到LANA-1，尽管其中一名患者有病毒周期蛋白的PCR证据。原发性肺动脉高压患者的丛状病变在组织学和免疫组织化学上与皮肤卡波西肉瘤病变相似。结论：导致重度肺动脉高压及丛状病变形成的触发因素和分子机制谱明显较广，包括遗传因素和表观遗传因素。我们的数据表明，感染嗜血管病毒HHV-8可能在原发性肺动脉高压中起致病作用。
BACKGROUND: Severe pulmonary hypertension constitutes a group of diseases characterized by complex, lumen-occluding vascular lesions that develop in genetically susceptible persons. The only viral infection associated with severe pulmonary hypertension has been that due to human immunodeficiency virus type 1, but neither the viral genome nor viral antigens have been demonstrated in pathologic lesions.METHODS: We examined lung-tissue samples from 16 patients with sporadic primary pulmonary hypertension and 14 patients with secondary pulmonary hypertension for evidence of infection with human herpesvirus 8 (HHV-8). HHV-8 infection was ascertained immunohistochemically with use of an antibody directed against latency-associated nuclear antigen 1 (LANA-1), and a polymerase-chain-reaction (PCR) assay was performed on lung DNA to detect the viral cyclin gene of HHV-8. Sequence analysis was also performed.RESULTS: In lung tissue from 10 of 16 patients with primary pulmonary hypertension (62 percent), cells within the plexiform lesions as well as cells outside the lesions were positive for LANA-1 on immunohistochemical analysis. Tissue from the same 10 patients contained viral cyclin on PCR analysis. No LANA-1 was detected in lung tissue from patients with secondary pulmonary hypertension, although one such patient had PCR evidence of viral cyclin. Plexiform lesions from patients with primary pulmonary hypertension had a histologic and immunohistochemical resemblance to cutaneous Kaposi's sarcoma lesions.CONCLUSIONS: The spectrum of trigger factors and molecular mechanisms leading to severe pulmonary hypertension and the formation of plexiform lesions is apparently wide, including both genetic and epigenetic factors. Our data suggest that infection with the vasculotropic virus HHV-8 may have a pathogenetic role in primary pulmonary hypertension.