Induction of HHV-8 lytic cycle replication by inflammatory cytokines produced by HIV-1-infected T cells
Induction of HHV-8 lytic cycle replication by inflammatory cytokines produced by HIV-1-infected T cells
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DOI：
10.1016/s0002-9440(10)65069-9
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发表时间：
2000-06-01
影响因子：
6
通讯作者：
Foreman, KE
中科院分区：
文献类型：
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作者：
Mercader, M;Taddeo, B;Foreman, KE
人疱疹病毒8 （HHV-8）是一种γ - 2疱疹病毒，在卡波西肉瘤（KS）、原发性积液性淋巴瘤和多中心Castleman病中一致发现。虽然HHV-8感染似乎是必要的，但如果没有其他辅助因子的参与，它可能不足以促进KS的发展。一个潜在的重要辅助因子是HIV-1， HIV-1感染的细胞产生HIV-1相关蛋白和细胞因子，这两种蛋白和细胞因子都被证明可以促进体外KS细胞的生长。虽然HIV-1对KS的发展并不是绝对必要的，但KS是艾滋病患者中最常见的肿瘤，而艾滋病-KS被认为是一种特别具有侵袭性的疾病。为了确定HIV-1是否可以通过调节HHV-8的复制（而不是通过诱导免疫缺陷）参与KS的发病机制，我们将HIV-1感染的T细胞与HHV-8感染的细胞系BCBL-1共培养。结果表明，通过裂解期mRNA转录物的产生、病毒蛋白和子代病毒粒子的检测，由hiv -1感染的T细胞产生的或响应于hiv -1感染的T细胞产生的可溶性因子诱导了HHV-8复制。通过关注共培养系统中产生的细胞因子，发现几种已知在体外KS细胞生长和增殖中起重要作用的细胞因子，特别是Oncostatin M、肝细胞生长因子/分散因子和干扰素- γ，当单独添加到bccl -1细胞中时，可诱导HHV-8裂解复制。这些结果表明，特定的细胞因子可以通过HHV-8的再激活在KS的发生和发展中发挥重要作用。因此，HIV-1可能通过促进HHV-8复制，从而增加局部HHV-8病毒载量，比之前认识到的更直接地参与KS。
Human herpesvirus 8 (HHV-8) is a gamma 2-herpesvirus consistently identified in Kaposi's sarcoma (KS), primary effusion lymphoma, and multicentric Castleman's disease. Although HHV-8 infection appears to be necessary, it may not be sufficient for development of KS without the involvement of other cofactors, One potentially important cofactor is HIV-1, HIV-1-infected cells produce HIV-1-related proteins and cytokines, both of which have been shown to promote growth of KS cells in vitro. Though HIV-1 Is not absolutely necessary for KS development, KS is the most frequent neoplasm in AIDS patients, and AIDS-KS is recognized as a particularly aggressive form of the disease. To determine whether HIV-1 could participate in the pathogenesis of KS by modulating HHV-8 replication (rather than by inducing immunodeficiency), HIV-1-infected T cells were cocultured with the HHV-8-infected cell line, BCBL-1. The results demonstrate soluble factors produced by or in response to HIV-1-infected T cells induced HHV-8 replication, as determined by production of lytic phase mRNA transcripts, viral proteins, and detection of progeny virions. By focusing on cytokines produced in the coculture system, several cytokines known to be important in growth and proliferation of KS cells in vitro, particularly Oncostatin M, hepatocyte growth factor/scatter factor, and interferon-gamma, were found to induce HHV-8 lytic replication when added individually to BCBL-1 cells. These results suggest specific cytokines can play an important role in the initiation and progression of KS through reactivation of HHV-8. Thus, HIV-1 may participate more directly than previously recognized in KS by promoting HHV-8 replication and, hence, increasing local HHV-8 viral load.