Kempf W, Adams V, Wey N, Moos R, Schmid M, Avitabile E, Campadelli-Fiume G
Department of Dermatology, University Hospital, 8091 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7600-5. doi: 10.1073/pnas.94.14.7600.
Earlier studies have shown that Kaposi sarcomas contain cells infected with human herpesvirus (HHV) 6B, and in current studies we report that both AIDS-associated and classic-sporadic Kaposi sarcoma contain HHV-7 genome sequences detectable by PCR. To determine the distribution of HHV-7-infected cells relative to those infected with HHV-6, sections from paraffin-embedded tissues were allowed to react with antibodies to HHV-7 virion tegument phosphoprotein pp85 and to HHV-6B protein p101. The antibodies are specific for HHV-7 and HHV-6B, respectively, and they retained reactivity for antigens contained in formalin-fixed, paraffin-embedded tissue samples. We report that (i) HHV-7 pp85 was present in 9 of 32 AIDS-associated Kaposi sarcomas, and in 1 of 7 classical-sporadic HIV-negative Kaposi sarcomas; (ii) HHV-7 pp85 was detected primarily in cells bearing the CD68 marker characteristic of the monocyte/macrophage lineage present in or surrounding the Kaposi sarcoma lesions; and (iii) in a number of Kaposi sarcoma specimens, tumor-associated CD68+ monocytes/macrophages expressed simultaneously antigens from both HHV-7 and HHV-6B, and therefore appeared to be doubly infected with the two viruses. CD68+ monocytes/macrophages infected with HHV-7 were readily detectable in Kaposi sarcoma, but virtually absent from other normal or pathological tissues that harbor macrophages. Because all of the available data indicate that HHV-7 infects CD4+ T lymphocytes, these results suggest that the environment of the Kaposi sarcoma (i) attracts circulating peripheral lymphocytes and monocytes, triggers the replication of latent viruses, and thereby increases the local concentration of viruses, (ii) renders CD68+ monocytes/macrophages susceptible to infection with HHV-7, and (iii) the combination of both events enables double infections of cells with both HHV-6B and HHV-7.
早期研究表明,卡波西肉瘤含有感染人类疱疹病毒(HHV)6B的细胞,而在当前研究中,我们报告艾滋病相关型和经典散发型卡波西肉瘤均含有可通过聚合酶链反应(PCR)检测到的HHV - 7基因组序列。为了确定HHV - 7感染细胞相对于HHV - 6感染细胞的分布情况,将石蜡包埋组织的切片与针对HHV - 7病毒体被膜磷蛋白pp85和HHV - 6B蛋白p101的抗体进行反应。这些抗体分别对HHV - 7和HHV - 6B具有特异性,并且它们对福尔马林固定、石蜡包埋组织样本中所含的抗原仍保持反应活性。我们报告:(i)在32例艾滋病相关型卡波西肉瘤中有9例存在HHV - 7 pp85,在7例经典散发型HIV阴性卡波西肉瘤中有1例存在HHV - 7 pp85;(ii)HHV - 7 pp85主要在卡波西肉瘤病变内或其周围具有单核细胞/巨噬细胞系特征性CD68标记的细胞中检测到;(iii)在一些卡波西肉瘤标本中,肿瘤相关的CD68 +单核细胞/巨噬细胞同时表达来自HHV - 7和HHV - 6B的抗原,因此似乎被这两种病毒双重感染。在卡波西肉瘤中很容易检测到感染HHV - 7的CD68 +单核细胞/巨噬细胞,但在其他含有巨噬细胞的正常或病理组织中几乎不存在。因为所有现有数据表明HHV - 7感染CD4 + T淋巴细胞,这些结果提示卡波西肉瘤的环境(i)吸引循环外周淋巴细胞和单核细胞,触发潜伏病毒的复制,从而增加病毒的局部浓度,(ii)使CD68 +单核细胞/巨噬细胞易受HHV - 7感染,以及(iii)这两个事件的结合使得细胞能够被HHV - 6B和HHV - 7双重感染。